Biological psychology (year one) Flashcards
How many neurons are in the brain and how many other neurons do each project to?
- 100 billion neurons
- Each projecting to 5000-10000 other neurons (i.e. literally trillions of connections – synapses)
Give a brief history of Psychology from 400BC to the 15th century
Plato (429-348 BC), ancient Greece: The brain is the organ of reasoning
Galen (AD 130-200), physician of the roman empire: proposed theory of brain function based on ventricles – not allowed to perform human dissection in Rome, observed cattle and oxon
Late 15th century we have first drawings of the brain (Leonardo da Vinci)
Describe the work and beliefs of Rene Descartes
French Philosopher and mathematician – he thought, therefore he was “Cognito; ergo sum”
Proposed that mind and body interacted in the pineal gland
However…Also realised much behaviour was mechanical, not requiring mental processing
Developed the concept of the automatic reflex
1596-1650
Give the divisions of the nervous system
Nervous system – CNS – brain/spinal cord
o PNS – ANS – sympathetic division/ parasympathetic division
SNS – sensory (afferent nervous system)/ motor (efferent) nervous system
Define afferent and efferent nerves and give an example
- Afferent : Sensory (afferent) nerve senses hot flame on skin (external sense organ). Afferents sense the heat and send rapid message to the spinal cord – conveys the message of heat pain!
- Motor (efferent) nerves respond by sending signal from CNS to muscles, to move hand away from flame
Describe the autonomic nervous system
- Some motor actions are involuntary and “automatic”
- e.g. heart and breathing (we don’t have to consciously think about these)
Describe the somatic nervous system
- The voluntary movements part
- e.g. moving your hand away from the flame
Describe the subdivisions of the ANS
- Two types of efferent nerves (CNS to internal organs)
• Sympathetic nervous system:
Autonomic motor nerves that prepare us for action (fight or flight)
• Think of this as responding to a stressor (a lion)
• e.g. heart rate increases
• Mobilises energy
• Parasympathetic nervous system:
Autonomic motor nerves that prepare us to relax
• Your peaceful restful state
• e.g. increases digestion
• Conserves energy
Explain how coordinates are given in neuroanatomy
- These are described in relation to the orientation of the neuraxis – which is the direction in which the CNS lies in relation to the spinal cord
- So if you imagine a line drawn through the spinal cord to the front of the brain
Give directional terms in neuroanatomy
- 3 axes: Anterior – posterior; Dorsal – ventral; Medial – lateral
- Dorsal : toward back of body, top of head
- Ventral : front of body or bottom of head
- Rostral/anterior : front end of body
- Caudal/posterior : towards tail/feet
- Medial : towards midline
- Lateral : away from midline
Define proximal/distal, bilateral/ipsilateral/contralateral
■ Proximal - close to CNS e.g. shoulders
■ Distal = far (distant) from CNS e.g. fingers
■ Bilateral: On both sides of the body or head
■ Ipsilateral: On the same side of the body or head
■ Contralateral: On the opposite side of the body or head
Give the area these directions refer to : ventromedial, dorsolateral, ventrolateral, dorsomedial
- Ventromedial : bottom middle of brain
- Dorsolateral : top left
- Ventrolateral : bottom left
- Dorsomedial : top middle
Give directional terms for brain sections
- Coronal : front to back (e.g slide of bread)
- Saggital : sliced vertically (e.g slicing apple)
- Horizontal : sliced right to left, horizontally (e.g burger)
Define cross section and midsaggital plane
- Cross section: A slice taken at right angles to the neuraxis
- Midsaggital plane: the plane through the neuraxis perpendicular to the ground; divides the brain in two symmetrical halves
What membranes protect the brain?
- dura mata (outer most layer, dense connective tissue)
- Arachnoid membrane (below dura mater, above pia mater)
- Subarachnoid space (contains cerebrospinal fluid)
Define cerebrospinal fluid and give its functions
- Fluid that fills the subarachnoid space, the spinal cord and ventricles of the brain
- CBF provides cushioning and support for the brain.
- People who have this drained suffer headaches and pain because their sensitive brains are not protected by the fluid.
- Excess CBF is continually absorbed into subarachnoid space, and sinuses which run through dura mata and drains into jugular vein
- If obstructed (e.g. a tumour between ventricles) CBF can build up in ventricles leading to the brain to expand. A condition called hypdrocephalus (water head)
Define the blood-brain barrier
- A semi-permeable membrane, which separates blood from CSF, providing a barrier that prevents many toxins from entering the brain from the bloodstream
- The degree to which therapeutic or recreational drugs (psychoactive drugs) work, depends on the ease with which they can cross the BBB
Give the 5 major structures of the brain
- Myelencephalon –medulla - largely comprises tracts between brain and spinal cord. (hindbrain)
- Metencephalon - pons and cerebellum. (hindbrain)
- Mesencephalon - tectum and tegmentum. (midbrain)
- Diencephalon – thalamus and hypothalamus. (forebrain)
- Telencephalon – cerebral cortex, limbic system and basal ganglia.(forebrain)
Describe the structure and function of the myelencephalon (medulla)
- Part of the hindbrain – most posterior part of the brain (brain stem)
- Oldest part = medulla oblongata (long marrow) – controls breathing, heart rate, salivation, vomiting
- If brain is cut above the medulla basic heart rate and breathing maintained. Damage to medulla = fatal
- Contains the reticular formation
- Involved in sleep, attention movement, and cardiac, circulatory and respiratory reflexes
Describe the structure and function of the metencephalon
- Part of the hindbrain – most posterior part of the brain
- Contains pons and cerebellum
- Pons (bridge) – enlargement of medulla, contains pontine nuclei – contains coeruleus and dorsal raphe = origin of noradrenergic and serotonergic containing fibrers in forebrain
- Cerebellum (little brain) important for sensorimotor control – control of movements
- Cerebellum damage can cause problems with decision making and language too
Describe the structure and function of the mesencephalon (midbrain)
- Part of the midbrain –two divisions (tectum and tegmentum)
- Tectum: dorsal of midbrain. Inferior colliculi (auditory function), superior colliculi (visual-motor function)
- Tegmentum: contains PAG – Primary control centre for descending pain modulation (contains enkephalins)
- Substantia nigra – important component of sensory motor system
Describe the structure and function of the diencephalon (forebrain)
- Up to this point brain could be likened to a tube that has evolved and enlarged from the spinal cord. Forebrain mushrooms out from so that it covers and surrounds the older ‘tubular’ brain, and adds greater complexity and new structutures – e.g. hypothalamus and thalamus
- Thalamus (Greek: inner chamber) – relays sensory signals from skin to prepare motor signals to cerebral cortex. Also involved in sleep, consciousness, alertness
- Hypothalamus – important for motivated behaviours (eating, sleeping and sexual behaviour)
Describe the structure and function of the telencephalon
- Everything else! Mediates most of the brains complex functions – voluntary movement, sensory input, cognitive processes – learning, speaking, problem solving
- Contains cerebral cortex AND subcortical structures – as well as important fibre bundles
Describe the structure and function of cerebral cortex
- Composed of small unmyelinated neurons
- Grey matter (other layers are composed of large myelinated axons and are white matter)
- Convolutions serve to increase surface area
- Large convolutions = fissures
- Small convolutions = sulci
- Ridges between fissures and sulci – gyri
- Longitudinal fissure separates hemispheres (it remains connected by cerebral commissure, inc corpus callosum)
- Contains the NEOCROTEX, and subcortical structures (hippocampus, limbic system, basal ganglia)
Describe the structure and function of the hippocampus
- 3 major layers
- Located at medial edge of cerebral cortex, folds back on itself in the medial temporal lobe
- Hippocampus means seahorse
- Major role in memory (spatial location memory)
Describe the structure and function of the limbic system
■ Limbic system – circuit of midline structures that circle the thalamus
■ – regulation of motivated behaviors
– Consists of mammillary bodies, hippocampus, amygdala, fornix, cingulate, septum
Describe the structure and function of the basal ganglia
- Motor system.
- Consists of amygdala, striatum (caudate nucleus + putamen), globus pallidus
- Extrapyramindal motor system (output fibres do not cross pyramidal regions of medulla)
- Degeneration of nigral-striatal pathway causes rigidity, tremor and slow movement in Parkinson’s disease
- Coordination of automated (without thinking) smooth, fluent movement.
Describe the structure and function of the neocortex
- It is the newest part of the cerebral cortex to evolve
- Cerebral cortex = largest part of telencephalon, composed of grey matter. Neocortex = largest part of cerebral cortex (90% of cerebral cortex is neocortex in humans). Other part is allocortex (contains hippocampus)
- Main difference is that neocortex has six layers – the most developed in its number of layers and organisation of the cerebral tissues (specific to mammals)
- Humans have large neocortex ratio, which correlates with complexity of behaviour. For a large neocortex to evolve brain must evolve in size to support it
- Central and lateral fissure divide each hemisphere into 4 lobes (frontal, parietal, temporal and occipital)
- lobes are not functional units
Give the four lobes of the cerebral cortex/ neocortex and give its functions
- Frontal lobe: motor cortex (precentral gyrus)
Complex cognitive functions (frontal cortex) - Temporal lobe: hearing and language
Complex visual patterns
Memory - Parietal lobe: somatic sensations e.g. touch (post central gyrus)
Orientation, location of objects - Occipital lobe: Visual processing
Describe the case study of HM
- Underwent bilateral medial temporal lobectomy
- EEG suggested seizures arose from foci in both left and right temporal lobes. Removal of one medial temporal lobe had proved effective in patients with unilateral temporal lobe focus – thus a decision was made to remove medial portions of both temporal lobes inc hippocampus, amygdala
- His generalised seizures stopped, and partial seizures reduced massively. Left surgery well-adjusted, normal perceptual and motor ability, normal intelligence…Memories for events predating surgery intact (more or less), short term memory pretty good too.
- BUT…total inability to form new long-term memories. In effect, H.M became suspended in time that day in 1953
Describe the case study of Phineas Gage
Entered under his left cheekbone, penetrated base of skull behind left eye socket, emerged at the top of the skull
Despite his horrific injury, within minutes Gage was sitting up in a cart, conscious and recounting what had happened
In 1868 Harlow wrote a report on the ‘mental manifestations’ of Gage’s injuries. He described Gage as “fitful, irreverent, indulging at times in the grossest profanity… capricious and vacillating” and being “radically changed, so decidedly that his friends and acquaintances said he was ‘no longer Gage’.”
The damage to Gage’s frontal cortex resulted in a loss of social inhibitions. Gage’s injuries provided some of the first evidence that the frontal cortex was involved in personality and behaviour.
Define neuronal processes
- Parts which stick out of the cell (axon or dendrite)
Define bipolar neurons
Bipolar:
1 dendrite or axon sending action potentials (APs) into the soma
1 axon sending APs out of the soma to the axon terminals
Define unipolar neurons
Unipolar:
One axon entering the soma.
The axon is branched such that APs can travel along the axon without going through the soma directly.
Define multipolar neurons
Multipolar:
Multiple dendrites sending APs into the soma
A single axon sending AP from the soma to the axon terminals.
Explain the history of “golgi”
- Name Golgi: comes from Italian neuroanatomist. Worked out a way of staining these structures for the first time, so they could be observed under a microscope. Now called Golgi method.
Describe and give examples of golgi 1 type neurons
- long axons, e.g. motor neuron
Describe and give examples of golgi 2 type neurons
- shorter axons project locally e.g. interneuron
How are multipolar neurons classed?
In terms of axon length
What are the main three purposes of neurons?
sensation, integration and action
Explain sensation
- to gather and send information from the senses such as touch, smell, sight etc.
Explain integration
- to process all information gathered, thus allowing us to take action.
Explain action
- to send appropriate signals to effectors
Muscles (cardiac, smooth, and skeletal)
Glands (e.g. blushing, sweating, etc.)
Explain how sensation works
- E.g. signalling danger through pain
- Goes to both spine (reflexes) and brain (either fearful withdrawal or more considered action)
Describe integration
- Sensory, emotional and cognitive
- Fear can bypass on the thalamus and cortex to cause a response – speeds up responses to danger
Explain action
This can be a reflex – doesn’t need cognition or emotion – but still involves integration in the spinal cord.
Involves:
• Sensory (afferent) neuron, unipolar – green.
• Integrative (interneuron), multipolar – red
• Motor (efferent) neuron, multipolar – blue.
Explain how neurons are classed in terms of function
In terms of function, we are interested in whether they feed information towards the CNS, within the CNS or away from the CNS.
• Bipolar: e.g. Vision served by bipolar neurons, carrying information from photoreceptors in the retina to the brain.
• Unipolar: e.g. Pain served by unipolar neurons, with information gathered by free nerve endings sent to the spinal cord.
• Multipolar neurons could either be interneurons (with short axons) that synapse onto other neurons in the CNS, or motor neurons (with long axons) that send information to muscle tissue.
• Sensory : towards
• Within : interneurons
• Away : motor neurons
Explain the function of sensory receptors
Sensory neuron:
- Vision receptor: often attached to a receptor. Receptors are needed when information is complicated e.g. light captured in the eyes – light is complex to analyse so a neuron by itself would not be able to do that, it needs special receptors (rods and cones in the retina). The neuron translates this complicated information into a simpler neural code or “language” – yes and no, like binary in computers, but the temporal patterns can be complex bursts and we don’t know exactly how neurons code the information they are carrying.
- Pain receptor: May not be attached to a separate receptor when the information is more simple, such as pain. Just needs to know if the tissue is damaged or not and the neuron can do this by itself – this type of neuron for pain is called a nociceptor.
- In both cases the information is sent to the brain.
Explain the function of motor neurons
- For motor neurons, the cell body (soma) tends to be in the spinal cord, but sometimes in the brainstem.
Give the name of regions with cell bodies/axons in the brain, spinal cord, CNS and PNS
- In the brain, regions with cell bodies are called nuclei, in the spinal cord are called horns, but in the PNS they are called ganglia.
- In CNS, regions with axons are called tracts, but in the PNS they are called nerves.
Define afferent neurons
When “affected” by something, it is something happening to you.
- neurons carry information from the body and the outside world into the central nervous system
Define efferent neurons
neurons carry commands from the central nervous system to muscles and organs
- “When you “effect” something you are changing it.
Define interneurons
- (relay, projection, local) connect and integrate neurons within the central nervous system
- Interneurons: when touch something painful (putting foot over the fire), sensation of pain causes automatic withdrawal reflex – occurs via interneurons (not requiring the brain). Have short axons.
Define and give the resting membrane potential
- If micro-electrodes are placed inside cell, charge is roughly -70mV (compared to outside the cell) – neuron is polarised
Explain the importance of selective permeability
- Selective permeability is important because it keeps cells functioning properly by letting only wanted molecules in and unwanted ones out. In addition to keeping the “bad stuff” out (e.g. bacteria, viruses), selective permeability is essential to the function of our nervous system. Without it, neurons would not “fire”.
Define polarisation
“Polarisation” is a term meaning charge difference.
Explain how the membrane is polarised
Ion is an electrically charged atom or molecule
- The membrane controls the environment within and around the neuron
- Selectively permeable membrane allows some substances through and blocks the passage of others
- Controls polarisation: the difference in electrical charge between the inside and the outside of the neuron
- These negatively charged proteins largely explain the balance of the other ions – as the next few slides will show.
Give the intracellular and extracellular ion contents
- Negative inside, positive outside
- K+, Na+, Cl- and chargerd proteins
How is the membrane potential created?
The membrane potential is partly a result of a balance between 2 opposing forces
- Diffusion = molecules distribute themselves evenly through the medium in which they are dissolved.
Follows concentration gradient: high to low
- Electrostatic pressure = force exerted by attraction or repulsion between charged molecules
Positive ions are attracted by negative charges and vice versa
Define electrostatic pressure
force exerted by attraction or repulsion between charged molecules
Describe the action of negatively charged proteins in resting membrane potential
- Membrane is impermeable to it
- ve charge provide electrostatic pressure to the other ions:
Describe the action of K+ ions in resting membrane potential
- Diffusion forces out of cell
- Electrostatic pressure forces inside cell
- Ions effectively remain where they are, some leak out
Describe the action of cl- ions in resting membrane potential
- Diffusion forces inside cell
- Electrostatic pressure forces out of cell
- Ions effectively remain where they are
Describe the role of na+ ions in resting membrane potential
- Diffusion forces inside cell
- Electrostatic pressure attracts inside the cell
- Some ions manage to move into the cell
How does Na stay outside the cell?
Membrane is only selectively permeable to Na
How does the membrane structure and properties support this potential?
- It has the same composition as any other cell membrane: fat. This composition is needed because the rest of the body is watery, and fat repels waters. This allows it to maintain integrity and not just get dissolved.
- The fat is made of phospholipids. They have a “head” that likes water (outside of membrane) and a “tail” that doesn’t like water (inside). These tails are attracted to each other (and so huddle together) but repel water that is inside and outside the cell.
What gets though the membrane?
- Water – because it is so small as a molecule it squeezes though, and it had no charge. Same with O2 and CO2. Ethanol is lipophilic (can use to clean fats). Blood Brain Barrier does not prevent ethanol, which is why it goes to the brain so easily – it’s soluble in the membrane.
What doesn’t get through the membrane?
- Ions – small molecules with a charge. + means positive charge. This prevents them getting through the bilayer.
- Amino acids and glucose are hydrophilic and don’t get through membrane – also too big.
What are the main molecule types in the membrane?
- Proteins (e.g for transport)
- Cholesterol (e.g for rigidity)
Name and give the locations of the four types of protein structures within the bilayer
Transmembrane: Channels (with pore) Integral: Span the membrane but have no pore. Inner membrane: Internal surface of membrane Surface: External surface of membrane
Give the function of transmembrane proteins
Transmembrane: call channels, with pore in the middle. These are the most important for transport. Can also act as pumps.
- Important for transport.
- Can be ion pumps, channels and carriers
Give the function of integral proteins
Integral: spans the membrane but has no hole. Proteins called “receptors” don’t have a hole in. Something binds to them (specific – key and lock) – causes chemical change inside.
Give the function of inner membrane proteins
Inner membrane: These are anchoring points that attach the membrane to internal cell structures.
- Attach the cytoskeleton (internal cell structure) to the membrane
Give the function of surface membranes
Surface: Same but external: sometimes have bit of sugars. Signalling to other cells (like flags). Some types also attach the cell to extracellular matrix (fibres) so that the cells are not just floating around but the cells have structure.
Describe how the sodium-potassium pump works
- Pump ensures the cell stays at -70uV
- For every 3 Na pushed out, 2 K are moved in.
- When you are resting, like now, most of the energy you are using in your body (i.e. the calories you are burning) is to power these pumps. That is how important they are. Every cell uses these but neurons use them to the advantage of communication.
- There are also other “leaky” channels (not pumps) which can let K+ through in theory, but in practice K+ stays inside the cell due to electrostatic pressure (positive ion attracts to negative charge inside the cell).
Explain how ion pumps work
Pumps use energy: they move ions AGAINST their concentration or electrical gradients
- The energy is in the form of ATP
- Critical for neuronal communication
How can ions and other molecules enter the membrane?
- Leak K+ channels just stay open all the time.
- Voltage gated is sensitive to the potential of the membrane.
- Some are ligand-gated – ligand acts as a key (from inside or outside)
- Stress: mechanical pressure can open the channels.
Give the names of the four types of channels
Voltage gated, ligand-gated (extracellular ligand), ligand-gated (intracellular ligand), stress activated
How do glia communicate?
- Glia “talk” not only among themselves, but also to neurons. They have receptors for many of the same chemical messengers used by neurons. These receptors enable them to eavesdrop on the neurons and respond in ways that help strengthen their messages.
- Communicate chemically (e.g ca+)
What happens to neurons without glial cells?
Neurons removed from rodents form very few synapses and produce very little synaptic activity
- When surrounded by glial cells (astrocytes) synaptic activity increases ten-fold
Give the three ways in which glial cells support neurons
Mobility, physical support, cleaning
Explain how glial cells support neuron mobility
- Support migration during development by providing scaffolding
- Support communication of information between neurons (action potentials)
Explain how glial cells provide physical support
- Form a cellular matrix to hold neural circuits together.
- Provide them with nutrition (e.g oxygen and glucose)
Explain how glial cells aid in cleaning
- Clear waste (dead, damaged for neurons e.g), e.g. glutamate is a neurotransmitter and must be cleared from synapses after use, otherwise can be toxic to neurons – possible cause of parkinsons
- Contribute to “pruning” unnecessary synapses (especially during brain development
Give the five types of glial cells
Astrocytes • Oligodendrocytes - CNS • Schwann cells – same function as 2 but in PNS • Microglia – important immune function • NG2 glia
Where can some glial cells be found?
NG2 glia, or polydendrocytes: precursor cells found in the mammalian central nervous system
Define and explain astrocytes
- Most numerous type
- Also the most complicated – have the most functions.
- 9 different types identified so far
- One single mature human astrocyte can contact ~2000 neurons and ~2,000,000 individual synapses
Describe the function of astrocytes
ensure that the environment around the neuron is conducive to electrical signals
- Support neurons providing the brain with structure (scaffolding)
- Removal of debris after injury or neuronal death (scavengers). Apoptosis means neural death.
- Neurotransmitter reuptake: promotes efficient signalling. Neurotransmitters are not meant to stay in the synapse so glia will mop these up.
- Guide migrating neurons and direct outgrowth of axons during development
- Regulate the properties of the presynaptic terminal
- Help form the blood-brain barrier
Describe the three ways in which astrocytes maintain the neuronal environment
• Nourishment
Produce chemicals (ions) needed by neurons
Supply glucose, oxygen from blood vessels
• Support and guidance
Provide physical support (including guiding migration and growth direction during development)
• Cleaning and protection
Clean up debris (phagocytosis)
Neurotransmitter re-uptake
Explain how astrocytes can provide guidance
- Astrocytes are critical regulators of neuronal migration, growth and survival during development — consistent with their well-accepted support role.
- A classic example is the role of radial glia in neuronal migration early during development. These specialized glia provide a temporary scaffold for the migration of newborn cortical and cerebellar neurons.
- Their long radial fibers extend from the ventricular to the pial surface and serve as permissive ‘guidance cables’ for neurons en route to their final target area in the brain. In addition to serving as a structural framework, radial glia provide important trophic support for migrating neurons.
Define phagocytosis
Phagocytosis clears away damaged neuron causing problems such as disrupting chemical processes taking place
Explain how astrocytes provide protection
Form part of the Blood-Brain Barrier
Semi-permeable barrier that controls what passes from the blood to the brain
Protects the brain from potentially harmful substances (pathogens, antibodies)
Explain the role and location of oligodendrocytes
In CNS
- Main function: improve message passing between neurons
- Neuron with axons – msg passed down – oligos make sure msg passed efficiently by wrapping axon in myelin sheath.
- Myelin: fat that provides electrical insulation – makes conduction more efficient, and the thicker the better. More thick = faster transmission.
Explain the role of schwann cells
- Similar function to oligos but in PNS
- The Schwann cell is completely wrapped around the axon in the periphery, with just one cell per section, unlike in CNS where one oligodendrocyte can contribute to many sections.
- Speed up the processing of the neuron by covering the axon in myelin
- Enable axonal regeneration (can only occur in PNS)
Explain the function and location of microglia
- Smallest hence the name microglia.
- Come from blood stem cells, unlike all other glia which originate from neural cell progenitors.
- main form of defence in CNS. Special treatment from immune system as CNS is so important - immune privileged - meaning CNS is able to tolerate the introduction of antigens or tissue grafts without eliciting an inflammatory immune response.
- Limiting the immune response is important because the CNS has limited capacity for regeneration. However, the CNS does not completely lack immune responses as once thought – rather it uses microglia instead.
- involved in pruning synapses if no longer needed, making plasticity more effective. When malfunction, associated with neurodegenerative diseases.
Explain the role of glial cells in Alzheimer’s disease
- Microglia are thought to play a role in Alzheimer’s
- Changes in morphology of glia
- The black spots represent areas where microglia have started to kill off neurons
Explain the role of glial cells in ALS (amyotrophic lateral sclerosis)
- Glia can be triggered to support the release toxic compounds
- This damages vulnerable neuron types
Explain the role of glial cells in multiple sclerosis
- caused by the malfunction of glia
- Specifically, failure of remyelination by oligodendrocytes
Explain the role of glial cells in neuropathic pain
- can be caused by activation of Schwann cells, microglia and astrocytes
- Glia release neuromodulators that induce plasticity and cause chronic pain
Explain how neuron-glial interactions in the spinal cord amplify chronic pain
- Neuron-glial interactions in the spinal cord for the amplification of chronic pain.
- Painful injuries such as nerve injury, arthritis, cancer, and treatment (chemotherapy) cause hyperactivity of nociceptors and secretion of glial modulators from their central terminals, leading to the activation of microglia and astrocytes in the spinal cord dorsal horn.
- Upon activation, microglia and astrocytes secrete neuromodulators to drive chronic pain by inducing synaptic and neuronal plasticity.
- Pre- and postsynaptic neurons can both “listen” and “talk” to microglia and astrocytes. CASP6, caspase-6.
Explain the role of glial cells in mood and developmental disorders
- Post-mortem findings showed reductions in glial cell numbers in some brain regions in patients with mood disorders.
- Specific reductions in oligodendrocytes have been reported for the amygdala in major depressive disorder (MDD)
- Related research has found a specific disruption of the paranode section where oligodendrocytes contact the neurons, affecting neuronal transmission and emotional processing
Explain the role oligodendrocytes play in regulating processes and how this can lead to emotional issues
- Oligodendrocytes have a role in regulating the development and periodicity of nodes of Ranvier, spaces of bare axon, which contain ion channels critical for action potential propagation along the axon.
- Animal studies have shown that stress induces disruption of paranode (where oligos contacts the axons of the neuron).
- It’s thought this could lead to disrupted axonal function, namely suboptimal conduction of action potentials along the axon, it’s harder for information to transfer within or between critical brain regions, such as within the amygdala, or between the PFC and amygdala – important because we know that mood is critically dependent on connections between prefrontal cortex and amygdala. May result in abnormal integration of emotional information.
Explain the history of Alzheimer’s disease
- Back at the start of the 20th century a German psychiatrist and neuropathologist called Alois Alzheimer was caring for a 51-year old patient, Auguste Deter.
Auguste presented with a range of behavioural symptoms which are pretty classic signs of dementia, including a loss of short-term memory, cognitive and language deficits, auditory hallucinations, delusions, paranoia and aggressive behaviour, etcetera - At the time this was believed to just be pre-senile dementia, however when she unfortunately passed 5-years after her diagnosis, an autopsy was conducted. During this, Alois found what we now know to be some of the most well-known microscopic and macroscopic markers of Alzheimer’s disease.
- Following this point, for quite a while most cases of pre-senile dementia were then classed as Alzheimer’s (unless there was another notable cause) and anything occurring in people that were slightly older was considered to be ‘senile dementia’.
- However, in autopsies conducted on people with senile dementia the same pathological markers were found as appear in Alzheimer’s – which led to Alzheimer’s then being classified into two types, early and late onset.
Give the characteristics of Alzheimer’s disease
- Most common form of dementia
- Two types : the first is early-onset AD (<65 years) (sometimes called familial) and the second is late-onset AD (>65 years) (or sporadic).
- The disease slowly progresses, with the changes in the brain starting to occur way before the onset of symptoms- this is why a lot of research is aiming at discovering early markers so we can prevent the disease before it progresses too far. Cognitive decline as we age is expected, however, AD goes one step beyond this and is very debilitating, resulting in a complete loss of independent function and treatments aiming at halting progression once symptoms show aren’t working, which is why we need to find something to target before the disease has progressed.
- Currently the treatments offered aim at improving cognition through increasing the neurotransmitters involved in memory and attention, however these are purely symptomatic treatments and do not halt the progression of the disease. No new drugs have been approved since 2003.
Give early and advanced symptoms of Alzheimer’s disease
Early symptoms Short-term memory loss Advanced symptoms Long-term memory loss Confusion Language impairment Personality changes Delusions Progressive disorientation and visuo-spatial deficits Depression and anxiety (commonly occur)
Explain how the pathology of the brain changes with Alzheimer’s disease
On the macroscopic level you can see that as AD progresses, there is an increasing amount of cortical atrophy (shrinkage) that occurs due to the neuronal death which is why the sulci (troughs) in the brain become enlarged.
Explain the microscopic markers of Alzheimer’s
- On the microscopic level, histological staining techniques reveal the classic pathology seen in AD – the same things Alois Alzheimer found.
Explain amyloid plaques
- amyloid (senile) plaques, which are made up of peptides called Amyloid- (A).
- This comes from the breakdown of a protein (amyloid precursor protein), which should be broken down to make peptides which are neuroprotective, however it can also be broken down through another pathway and form AB.
- In AD it’s thought that there is an increase in the second pathway, and we can’t clear all the AB so it will build up and aggregate to form these plaques. It’s thought that AB is toxic because of it binding to neuronal receptors and causing synaptic dysfunction
Explain neurofibrillary tangles
- which accumulate within the neurons.
- These are made up of a protein called Tau, which when healthy helps with transporting things like neurotransmitters down to the synapses, but when it undergoes the change it does in AD, then it causes synaptic dysfunction again.
Explain the role of microglia in Alzheimer’s
These act as the immune cells in the brain and will usually destroy any pathogens/problematic build ups of protein- in this picture they are surrounding the amyloid plaques (green).
Explain the link between inflammation and Alzheimer’s
- inflammation in the brain is bad because our CNS neurons don’t regenerate
- There were clear markers of inflammation in AD patients found in both the brain and the CSF and microglia were found to be in what is known as an activated state – all clear signs of inflammation.
- Inflammatory factors are shown to increase in both the brain and cerebrospinal fluid (CSF) of AD patients
- Increase in activation of microglia – our main form of immune defence in the CNS.
Express receptors responsible for detecting foreign pathogens
Release inflammatory factors
Express receptors to detect inflammatory factors
Explain the change in glial cell morphology from ramified microglia to amoeboid microglia
- normally microglia exist in what was considered to be an inactive state, otherwise known as ramified microglia and are located in the parenchyma of the healthy brain.
- Although it was called an inactive state, it has been demonstrated that the processes of ramified microglia constantly survey the environment for chemical signals.
- Alterations in this environment lead to rapid morphological changes, as well as upregulation of receptors necessary for the detection of inflammatory factors. These changes lead to the microglia becoming an amoeboid shape instead, which then allows them to go and engulf any harmful proteins/pathogens/dead neurons in a process known as phagocytosis.
What can happen when microglia are in an amoeboid shape?
When they are in the amoeboid shape, they can be both neuroprotective or neurotoxic.
Explain the interaction between neurons and microglia
- Part of the role of neurons is to maintain the ramified microglial state through expression of proteins on their membranes and release of signalling molecules. The activation of microglia is normally restricted to stop too much neuronal damage.
- Neurons will express/release chemical ‘OFF’ signals constitutively (at a constant level) to keep the microglia from activating. However, ‘ON’ signals, will be produced on demand to instigate microglial activation – this occurs when neurons are stressed or damaged.
Explain the beneficial role of microglia activation in Alzheimer’s disease
- The reason this occurs is because in AD, amyloid-β (Aβ) which makes up the plaques has been shown to activate a cascade of signals that results in something called opsonization (which means targeting something for destruction by immune cells).
- This signal is detected by scavenger receptors microglia processes and results in them becoming activated and migrating towards the plaques, so they surround them and engulf amyloid via phagocytosis.
- If you ablate the expression of the scavenger receptors responsible for detecting opsonization, this results in an increase in the deposition of Aβ, and if you up-regulate the expression of the receptors it results in increased clearance of the plaques.
Explain animal research findings for the role of microglia in amyloid plaque detection
- One of the receptors expressed on microglia, called TREM2, is able to detect the amyloid plaques.
- Genetic mutations in this receptor which reduce its activity results in a reduction in the ability of the microglia to engulf amyloid-β and enhances the expression of pro-inflammatory factors. This leads to accelerated accumulation of amyloid and neurotoxicity (due to the inflammation and the increased amyloid).
- However, if you increase the amount of TREM2 expressed by microglia, it increases the responsivity of the microglia, so it takes less time for the microglia to be activated and for phagocytosis to occur.
- Since the phagocytic activity of the microglia is increased, the amount of amyloid plaque decreases.
- Which means that fewer microglia are activated because the other microglia are able to work quicker. This reduces inflammation and the amount of amyloid plaque that can be seen, which was correlated with improvements in the memory deficits seen in the mouse model the team used.
Explain human research studies into the role of microglia and amyloid
- Paul Edison (2018) detected a significant 20-35% increase in microglial activation in AD patients, as we would expect. A significant 2-fold increase of amyloid was also found in the same cortical areas.
- Another study was aiming to see if there is correlation between cognitive impairment and the pathology. So they used a test called the mini-mental state examination (MMSE) which is a diagnostic tool used to measure cognitive impairment. They found that scores on the MMSE in the AD patients were inversely correlated with the cortical microglial activation, but not amyloid load. So this may support the idea that microglia are neurotoxic (i.e. cause neuronal damage) as scores worsen the more activation there is.
Explain the detrimental role of microglia activation in Alzheimer’s
- During this the microglia release pro-inflammatory factors which are partly responsible for the neuronal damage/death.
- In doing so, the neuron will die causing it releases factors that act as ON signals for the microglia, which further activate the microglia. This results in a loop of continuing neuronal damage which is very detrimental.
Describe and explain post synaptic potentials
- The typical resting membrane potential inside the neuron is -70 mV
- However this can influenced by incoming signals from other cells which can either:
- Further polarise the cell (more negative) this inhibits the likelihood of an action potential occurring
- Else it can depolarise the cell (make it more positive, i.e., towards neutral) which is excitatory and increases the chance of the cell generating an action potential.
Describe how post synaptic potentials travel across the neuron
- Post synaptic potentials travel across the neuron almost instantaneously (rapid)
- But as they travel they decrease in size (decremental).
Explain depolarization
If the cell receives excitatory input it will depolarise. - If the membrane potential at the Axon Hillock (red square) achieves the threshold of excitation (commonly -50 to -55 mV) the cell will fire.
- However, remember that the incoming signals can only travel short distances before they expire (decremental)
Explain hyperpolarization
- If the cell receives inhibitory input it will hyperpolarise to become even more negative.
- If the inside of the cell is more negative you’ll need a bigger stimulus to reach the threshold.
- Therefore the cell is inhibited from firing by hyperpolarisation
Explain integration of signals and how it works
- The resting potential of post-synaptic cell is polarised (-70 mV).
- Cells are usually contacted by many incoming PSPs.
- Each PSP could have excitatory or inhibitory influences (usually many of each), by depolarising or hyperpolarising the post-synaptic neurone (respectively).
- The effect of these PSP’s transmit across the neuron decrementally.
- The balance between excitatory and inhibitory input (the net effect) determines whether an action potential fires
- If the net effect transmitted to the axon hillock results in depolarisation to the threshold of excitation then an action potential will fire.
Explain the way in which action potentials are generated
When the integration of inputs achieves the threshold of excitation at the axon hillock, it initiates the generation of an action potential (AP).
The AP itself is described according to various components or phases:
• Depolarisation: Na+ channels open, influx of Na+ into cell.
• K+ channels open, K+ begins to leave cell.
• Peak : Na+ channels begin to close, K+ channels still open.
• Repolarization: Na+ stops entering cell, K+ ions move out.
• Hyperpolarization: K+ channels start to close but some K+ ions continue to move out of cell.
Why do we need action potentials?
This means that you need a non-decremental way to send information long distances.
- AP are large swings to opposite polarity
- Non-decremental so able to carry the original signal for long distances
Explain action potential propagation
- Action potentials are able to transvers large distances without losing the integrity of the signal (the original large swing in polarity is maintained).
- This is due to a cascading effect whereby the rapid depolarisation at the axon hillock leads to achievement of the threshold of excitation in the next section of the axon and this continues down the length of the axon.
Explain how the speed of transmission is affected by the anatomy of the axon
- Myelinated axons (up to 150 m/s)
- Non-myelinated axons (0.5-10 m/s)
Describe how neurons communicate
- Pre-synaptic terminal buttons to post-synaptic soma, axon or dendrites
- Axon to dendrites : axo-dendritic
- Axon to soma : axo-somatic
- Axon to axon : axo-axonic
Describe electrical synapses
- Electrical synapses are the result of a narrow gap between the pre- and postsynaptic neurons known as a gap junction.
- The close proximity (e.g., 4 nm) means the cytoplasm of the two cells are interconnected
- This permits electrical signals (and even small molecules) to pass directly from one cell to the next.
- This system is FAST (faster than chemical synapses) and BIDIRECTIONAL.
Give the key functions of electrical synapses
- Electrical synapses in the cerebral cortex allow each network of inhibitory neurons to fire in a highly coordinated way
- They may relate to rhythmic activity in the cortex.
- The high speed of electrical synapses transmission means they are important for reflexive processes.
- A downside of electrical transmission is that there is no opportunity for ‘gain’ i.e., a small signal cannot bring about a large response.
Describe chemical synapses
- This method of transmission depends on the release of chemicals from presynaptic cell, which are received and have an effect on post synaptic cell.
• In chemical synapses the pre- and post-synaptic membranes are divided by the synaptic cleft (20 nm wide).
• The post-synaptic membrane contains receptors that can receive the chemical transmitters that will be used to communicate from the pre-synaptic cell.
Explain transmitter release in chemical synapses
Neurones contain bubble like structures that are filled with chemicals called vesicles.
- The AP stimulates the influx of Ca2+, which causes synaptic vesicles to:
• Attach to the release sites
• Fuse with the plasma membrane
• Expel their contents into the synaptic cleft.
These chemicals can act as a form of transmission or communication by affecting the post-synaptic neurone.
Explain neurotransmitter receptors
• NT receptors are membrane spanning proteins.
• The part exposed to the extracellular space recognises and binds the transmitter to bring about a function that has an effect on the target cell.
• There are different types of receptor. 2 of the most common:
1. Ligand-gated ion channels - direct
2. G-protein-coupled receptors - indirect
Explain inhibitory and exhibitory synapses
According to the effect on postsynaptic cell, synapses can be:
- Excitatory (+ e.g., Na+, Depolarising)
- Inhibitory (e.g.c Cl-, hyperpolarising)
- Depending on the type of ion channel which opens, the postsynaptic cell membrane becomes either depolarised or hyperpolarized.
• This decreases or increases the likelihood of the receptor neurone firing with an AP.
• You recognise this because, once again, we are talking about Post synaptic potentials.
Describe the actions of neurotransmitters
A neurotransmitter (NT) is a chemical released by the presynaptic neuron to bring about an effect in the post-synaptic neurone.
A NT:
- Must be produced within a neuron
- Must be released when the neurone is stimulated
- When released, it must act on a post-synaptic receptor and cause a biological effect.
- Once released it must be inactivated.
- If the chemical is artificially applied on the post-synaptic membrane, it should have the same effect as when it is released by a neuron.
Give the main groups of small-molecule neurotransmitters and give examples
- Amino acids e.g glutamate, GABA, aspartate
- Monoamines e.g dopamine, epinephrine, norepinephrine
- Acetylcholine
- Unconventional neurotransmitters e.g soluble gasses (nitric ocide), endocannabinoids (anadamide)
Describe amino acid neurotransmitters
- Obtained from proteins we eat or synthesized (GABA from glutamate)
- Found at fast-acting direct synapses
- Glutamate : most prevalent excitatory neurotransmitter (AMPA and NMDA)
- GABA : most prevalent inhibitory NT
- Balance of arousal and quiesence
Describe neuropeptides
- Large molecules (3 to 40 amino acids)
- Over 100 identified, loosely grouped
- E.g pituitary peptides, brain-gut peptides
Explain how NT action is terminated
- Receptors cannot withstand exposure to neurotransmitters constantly
- If they are overexposed to NT all the time their ability to respond is impaired (desensitise)
- Therefore, a mechanism is required to clear unused NT from the cleft to prevent residual activation
- Enzymatic degradation
- Reuptake
- Diffusion
- glia
Explain how enzymatic degradation works
- Breakdown of NT into parts which do not cause activation in post synaptic membrane
- E.g acetylecholine broken down into acetate and choline by acetylecholinesterase
Explain how reuptake works
- NT molecule is reabsorbed by presynaptic neuron and repackages into vesicles for reuse
Explain colocalization
- It was once believed that each neurone synthesises and releases only ONE neurotransmitter
- Now it is known that many neurones contain more than one neurotransmitter
- Usually one small NT and a neuropeptide
Define agonists and antagonists
- Agonists increase or promote activity
- Antagonists decrease or inhibit the activity
Explain the process of fertilisation
Zygote (at fertilisation) – 2 blastomeres – 4 blastomeres – morula (72 hours later)
Explain the development of a morula
Morula – blastula – trophoblast (embeds in endometrium)
Explain how the morula develops into the nervous system
Layers in the embryonic disk contain nervous system cells (ectoderm, mesoderm, endoderm) : collectively neural plate
Give the name of and explain the first observable development of the nervous system
First observable development of the nervous system is the induction of the neural plate.
- 3 weeks after conception, patch of the ectoderm becomes distinguishable as neural plate.
- The neural plate develops to form:
- neural groove
- neural tube
Explain how the anterior end of the neural tube develops
- The anterior end of the neural tube develops 3 swellings that become the forebrain, midbrain and hindbrain (7 weeks - Day 40)
- Neural proliferation: At this stage rapid cell division occurs in the ventricular zone of the neural tube (nearest the ventricle).
Give the ventricles, subdivisions and principle structures of the forebrain, midbrain and hindbrain
- Forebrain : ventricle = lateral, subdivision = telencephalon, principle structure = cerebral cortex/ basal ganglia/ limbic system
- Midbrain : cerebral aqueduct, subdivision = mesencephalon, principle structure = tectum, tegmentum
- Hindbrain : ventricle = fourth, subdivision = metencephalon, myencephalon, principle structure = medulla oblongata
Explain how cell migration leads to the development of the central nervous system
- Once the cells have been created in the ventricular zone they migrate to appropriate location
- During this process they are still immature neurones (no dendrites or axons).
- Glia make scaffolding for migration
- After migration, cells aggregate to form various neural structures.
Explain how cell differentiation leads to the development of the central nervous system
- Once neurones aggregate in desired location differentiation occurs.
- Axons and dendrites may begin to grow as cells differentiate depending on purpose and location
Explain how neuronal death leads to the development of the central nervous system
- During gestation, more neurones are produced than required (50%)
- ‘Superfluous’ cells die
- This can be
• Pre-programmed (apopstosis)
• Synaptic rearrangement: unnecessary connections die (necrosis)
Describe the brain by 20 weeks
-By 20 weeks the brain is about 5 cm long and it has the basic shape of a mature brain
Describe postnatal development and how this occurs
- At birth: 350-400 g -Adult: 1300-1400 g
- Much of the growth happens in the first 2 years
- This increase in size is NOT due to increase in number of neurones
- Three other kinds of growth
• Synaptogenesis
• Myelination
• Increasing branching of dendrites
Describe the process of synaptogenesis and its importance
- Synaptogenesis is important because the number of connections between neurones is assumed to be an indicator of the brain function or capability.
- There is a rapid increase in synaptogenesis in the cortex after birth.
- But there are differences between regions (i.e., in visual and auditory cortices proliferate at 4 months whereas frontal cortex develops more at 2 years)
- Many synapses that form early in development are eventually lost; overproduction of synapses in the young brain may contribute to greater plasticity with relevance for learning
Explain how myelination leads to the development of the CNS
- Myelination increases the speed of axonal conduction and parallels functional development
- Myelination of sensory areas occurs in first few months
- Then myelination of motor areas
- Myelination of prefrontal cortex continues into adulthood
Explain how dendritic branching leads to the development of the CNS
- Rapid process
* Changes can be observed in seconds
Explain how pruning leads to the development of the CNS
- Pruning: The selection of the pruned terminal arbours follow the “use it or lose it” principle seen in synaptic plasticity.
- This means synapses that are frequently used have strong connections while the rarely used synapses are eliminated
- Pruning is carried out by microglia
Describe the effects of experience in post natal development
- Most experiences are time dependent: the effect of a given experience on development depends on when it occurs during development
- Leads to the concept of early development as a ‘window of opportunity’
- Sensory deprivation: animals reared in the dark have fewer synapses in visual areas and as adults have problems perceiving depth.
- Enrichment: thicker cortices with more dendrites and more synapses per neurone
Explain some neural mechanisms of autism
1- Autistic individuals spend less time looking at faces and remember faces less well
Research has shown that brain areas that respond to faces (fusiform gyrus) are less active
2- Mirror neurones: these neurones fire when you see somebody performing an action
They help one understanding the intentions of others. Children with autism have deficient mirror neurone function
Explain and describe Williams syndrome
- Intellectual disability and heterogeneous pattern of abilities and disabilities (similar to autism)
- In many aspect opposite to autism: Sociable, empathetic and talkative
- Very good linguistic and musical abilities
- Serious cognitive deficits: attention, spatial abilities. Terrified of apparently mundane
- Impaired spatial abilities and underdeveloped parietal and occipital cortices; this appears to be due to a major mutation in chromosome 7
Give some of the ways of imaging the brain
Contrast X-rays • cerebral angiography • Computer Tomography (CT) • Magnetic Resonance Imaging (MRI) • (Functional) MRI • Positron Emission Tomography (PET) • Electroencephalography (EEG) • Magnetoencephalography (MEG) • Transcranial Magnetic Stimulation (TMS)
Define EEG
- Electroencephalography, (EEG) is the measurement of electrical activity from the brain using electrodes located on the scalp.
- Electrodes measure voltage fluctuations which directly result from the flow of ions across cell membranes of neurons and explain EEG
Give some components of EEG machines
- Electrodes: metal contact disc of 0.7-1.0 cm diameter (Ag/AgCl, Au, Sn)
- Electrodes connect to a powerful amplifier, which also
digitizes signals and conveys them to a processing computer.
Explain the neural basic of EEGs
Action Potentials:
- Rapid, transient, all-or-none swing in polarity of ~100mV and a duration of 1ms that propagate from the body to the axon terminal of a neuron.
- Not sufficient to be recorded by EEG electrode
Post Synaptic Potential:
• Action Potential reaches the axon terminal and releases neurotransmitter.
• Neurotransmitter binds to the receptor on the postsynaptic neuron which becomes (de)polarised.
• This causes a voltage change (PSP) which can last tens or even hundreds of milliseconds and may summate with other PSP’s nearby at similar time.
The source of EEG recorded activity
Explain how EEG signals are generated
- Pyramidal neurons are spatially aligned and perpendicular to the cortical surface.
- EEG signals stems from synchronous activity of large (~1000s) groups of neurons close to each other and exhibiting similar patterns of activity
- Thus, EEG mainly represents postsynaptic potentials of pyramidal neurons close to the recording electrode.
- Termed: Local field potential
Explain ongoing EEG activity
- Ongoing brain activity is characterised by fluctuating of local field potentials (measured as changes in voltage) which rises and fall in a rhythmic fashion over time
- This is what we measure and observe when using EEG
- Each line on an EEG recording represents the oscillating voltage occurring underneath the electrode.
- By using many electrodes across the head we can pick up an idea of the different electrophysiological activity occurring across the brain.
Explain brain computer interfaces
- Brain-computer interfaces are direct pathways of communication between the brain and some external device.
- They can take many forms depending on hardware and software.
- External/or internal brain sensor or stimulator.
- Connected to hardware (e.g., machinery, neuro-prosthetics), or computer software.
- Limitless clinical and commercial applications
Give the principles of BCl
- Whenever we think, move, feel or remember something, specific groups of neurons, often grouped together in particular regions of the brain, are activated.
- This activation forms a pattern, and the dynamics of the pattern can be studied using signal processing methods.
- Brain communication via action potentials relies on post-synaptic potentials which cause a local field potential.
- This LFP activity can be detected, and even interpreted in virtually real-time, in order to command output -or receive input - from an external device of some kind.
Give the general architecture of BCI
- BCI bypasses the brain’s normal pathways, e.g., via peripheral nerves, muscles or sensory organs, to bring about an application.
Explain output BCIs
- OUTPUT BCIs = devices that convert human intentions in the form of electrophysiological signals to overt device control. E.g., neuroprosthetic.
• Electrodes capture electrophysiological activity of motor cortices and transmit to a computer in real-time (or close to).
• This signal is decoded according to a complex machine learning algorithm which is tailored to the patients brain patterns.
3.The software estimates the most appropriate action and send the command to the neuroprosthetic to perform the action (e.g., grasp fist with X degree of force).
Explain input BCIs and give an example
Explain input BCIs and give an example
- INPUT BCIs = devices that translate external stimuli such as light or sound into internally perceived visual or auditory perceptions
Most common example of sensory prosthetic is the cochlear implant.
Patients lack cochlear hair cells that transduce sound into neural activity.
- Example : cochlear implant
• Sound processor behind the ear captures sound and turns it into digital code.
- This is transmitted to the internal implant.
- The implant converts the digitally-coded sound into electrical impulses and sends them along an electrode array in the cochlea (the inner ear).
- The implant’s electrodes stimulate the auditory nerve, which then sends the impulses to the brain where they are interpreted as sound.
Explain non-invasive BCIs
• Non-Invasive BCIs typically include equipment that can sense changes in brain activity in (or close to) real time. • Essentially this means EEG. • Comfortable • Wireless systems available. • Lo-cost (relatively speaking ) • produce poor signal resolution o (skull interferes with signals)
Explain invasive BCIs
ECoG (Electrocorticography) is a electrode array that can be implanted on top of relevant cortex (e.g., motor regions) to record activity from specific parts of the brain.
The advantage is that the signal is recorded before it is diffused by the skull (subdural)
Not signal taken from within the brain parenchyma itself.
- Micro electrodes involve a tiny array of needle electrodes actually inserted into brain tissue (e.g., motor cortex) to record field potential directly as they occur.
Most accurate – but more risky
Explain how BCIs translate information into action
● Decoding the brain activity that underpins intention of movement is a huge research target. This has clinical implications (paralysis, locked-in syndrome) and also leisure and commercial applications (e.g., gaming etc.)
- μ–rhythm (mu) is a distinctive rhythmic electrophysiological activity that we observe over the motor cortices.
- Research shows that movements or imagination of movements suppress the μ–rhythm of the contralateral motor cortex.
- This activity and supression phenomenon occurs even in people who have a compromised peripheral motor system (e.g., spinal-cord injury etc. )
- This makes μ–rhythm activity a research target for BCI‘s, aiming to control a prosthetic which is designed to imitate or replace motor capability.
Define and explain Parkinson’s disease
- A brain disorder characterised by cell death.
- Mechanisms likely include dysfunctional neurotransmission of dopamine in specific brain regions.
- When a significant proportion of dopaminergic motor neurons die we see a huge drop in dopamine levels. This inhibits the ability for remaining neurons to generate and transmit a signal which causes characteristic Parkinsonian gait and symptoms such as tremors.
Define and explain Alzheimer’s disease
- Again, AD represents a neurodegenerative brain disorder characterised by cell death.
- Causes are not fully known, but likely include genetic and environmental factors.
- Like with PD, cell death may be due to complex changes neurotransmission systems.
- Cognitive decline appears in patients before extensive neuronal loss. Therefore, synapse dysfunction is likely to be an early cause.
Define and explain autism spectrum disorder
- ASD is a diverse neurodevelopmental condition, arguably defined by two core symptoms: social deficits and stereotypical behaviour.
- An imbalance between excitation and inhibition in neocortical areas has been proposed as a key process in ASD pathogenesis (Baudouin et al. 2012).
- Synaptic dysfunction in ASD could be caused by alterations of glutamate receptors. Potentially due to underlying genetic cause
Explain the interaction between cortisol and insulin
- Chronic stress leads to dysregulation of the HPA and (usually) elevated levels of basal cortisol
- Cortisol increases glycemia (blood glucose level) and amino-acids in the blood
- Glucose and amino-acids stimulate secretion of insulin from b-cells of Langerhans islets to transport the glucose into cells (therefore, high insulin levels in the blood)
- Due to too much of glucose in the cells, the inner part of insulin receptors undergoes molecular changes making them less effective, and glucose cannot enter cells in spite of high insulin
Describe the lipid properties of hormones
• Lipid insoluble:
• proteins and peptides (e.g., insulin)
• derivates of amino acid tyrosine (e.g. thyroid hormones)
• lipid insoluble hormones are chains of amino acids (valine,
o leucine, proline…)
• proteins (>100 amino acids) or peptides (<100 amino acids)
- Lipid soluble: have a common precursor cholesterol
- (steroid hormones, e.g., aldosterone, cortisol, testosterone…)
- Cholesterol is a fat-like molecule, abundant in cell membranes.
Define hormone and give some types
- A chemical agent secreted by a group of cells and acting at a distance
from the site of origin (a gland, tissue).
• Endocrine hormones: secreted by specialised cells or gland into the
circulating blood (e.g., insulin, corpus luteum)
• Neuroendocrine hormones: secreted by neurons into circulating blood
(e.g., hypothalamic releasing hormones)
• Cytokine hormones: peptides secreted by tissues (e.g., leptin)
Explain the link between hormones and receptors
• A key and the lock: hormones can affect a cell only if cell has a receptor that fits.
• Hormone receptors are large proteins, and a cell
usually needs to have 2000 or more receptors to be
engaged by a hormone
• Down-regulation and up-regulation of receptors
is a tool to regulate bodily response to hormones
Give ways that hormones can affect tissues, organs and the brain
• Via ion channels (rare) and G protein-linked receptors
(peptides, proteins)
• Via binding to intracellular receptors and acting on DNA (steroids)
• Via direct actions on the cell nucleus (thyroid hormones)
Explain how G protein-linked hormones work
A receptor on outer side of membrane is activated by a hormone. It causes activation of alpha unit of G protein (GDP). Alpha unit detaches from beta and gamma units and activates various intracellular enzymes (adenylyl cyclase, phospholipase C and several other).
Explain the actions of steroid hormones
A steroid freely passes the cell membrane and binds to receptors in the plasma. The hormone-receptor complex binds to hormone-response element strand of DNA (promoter).
Explain thyroid hormone actions
- Thyroid and adrenal medullary hormones are derived from amino acid tyrosine. The hormones pass the cell membrane via carrier channels and enter the nucleus. There is a thyroid receptor on hormone sensitive element of some genes causing transcription of DNA into mRNA.
- Tyrosine-based hormones can activate or deactivate genes and lead to synthesis of new proteins
Name some hormones and their functions
- Hypothalamic releasing hormones: top level of regulation, growth
- Anterior pituitary hormones: second level of regulation
- Posterior pituitary hormones (vasopressin, oxytocin) – smooth muscle contractions
- Thyroid hormones (thyroxin T4, triiodothyronin) - metabolism
- Adrenal cortex hormones (aldosterone, cortisol, androgens) – metabolism, stress
- Adrenal medulla hormones (adrenaline, noradrenaline) – stress, emotions
- Pancreas (insulin, glucagon) – maintaining glucose level
- Sex hormones (estrogens, progesterone, testosterone) - reproduction
- Gastro-intestinal peptides (CCK, leptin, ghrelin, NYP): eating behaviour
Give hypothalamic connections
• With the brain stem and reticular
formation > autonomic system
• Anterior thalamus and limbic system
• Hypothalamic infundibulum area
(Endocrine control)
