Semester 1 Neuroscience Flashcards
What are the 2 areas of the nervous system?
Central Nervous System (CNS)
Peripheral Nervous System (PNS)
What do the 2 areas of the nervous system compose? (higher order organisms)
CNS:
- Brain and spinal cord
- Control centre for information processing and responding to sensory information
PNS:
- Cranial nerves
- Spinal nerves
- Ganglia (Dorsal root ganglia and autonomic ganglia)
What is a neuron?
It is the basic building block of the nervous system
- Receives stimuli
- Transmits nerve impulses or action potentials
- Activates muscles
Neurons in all species are the functional units of the nervous system, organised into a function network capable of:
- Response to stimuli
- Information processing
- Communication
Basic neuron structure?
Dendrites (located on cell body)
- Collect electrical signals and carry input to cell body
Cell body
- Integrates signals and generates an action potential
Axon
- Transmits signals over long distances from the cell body to the axon terminals
What is a neuronal network?
A series of neurons communicating with each other
Communication happens at the axons
Axon of one neuron will communicate with dendrite of other neurons
What is the differences in nervous systems caused by?
Differences amongst species are not due to the neurons, but due to how they are organised.
Also due to how well they propagate signals.
What organisms do not have a nervous system?
Sea sponges:
- Multicellular organism without a nervous system
What are invertebrate nervous systems specialised for?
They are specialised for:
- Stimulus/response
- Receptor/effector
- Reflexes
- Conditioned response
What are nerve nets and what is their structure ?
Simplest form of nervous system found in some invertebrates (hydras, jellyfish, etc)
Individual nerve cells exist in a net-like formation scattered in layers of body wall
Neurones exist in a loose network to allow for contraction and expansion of the body cavity
Nerve nets lack distinct central of peripheral regions, and anything that resembles a brain
Nerve nets have no associate activity, just reflexes (with action potentials)
However, neurones carry:
- Information from sensory organs that detect light, touch, or other changes from the environment
- These neurones in turn contact neurones that control movement of the organism, such as swimming
Nerve signals in a nerve net can travel in both directions
What is a nerve net?
Simplest form of nervous system in invertebrates like hydras and jellyfish
Consists of individual nerve cells in a net-like formation scattered in body wall layers
Found in invertebrates like hydras and jellyfish
Describe the structure and limitations of nerve nets.
Neurones are in a loose network, allowing body cavity contraction and expansion
Lacks distinct central or peripheral regions and anything resembling a brain
Only possesses reflexes with action potentials, no associative activity
How do nerve nets function in response to stimuli?
Neurones carry information from sensory organs detecting light, touch, or environmental changes
These neurones contact others controlling movement, like swimming
Nerve signals in nerve nets can travel in both directions
Which invertebrate species shows centralisation of the nervous system?
Sea stars display some centralisation of the nervous system
A ring of neurones is located in the centre with simple bundles of neurones (radial nerves) extending from the ring to the tip of each arm
Radial nerves form nerve nets permitting coordinated movement of each arm and the tube feet located on the surface of the arm
What is cephalisation and formation of the primitive brain?
In animals with bilateral symmetry, there is a clustering of neurones into ‘ganglia’ near the head of the animal to form a more complex system to integrate incoming/outgoing signals (seeing, hearing, tasting)
What is special about animals with bilateral symmetry?
With bilateral symmetry, 2 nerve cords run down the length of the body
This system allows more complex control of muscles for movement
Structure of cephalopods nervous system?
Cephalopods are invertebrates however display distinct CNS and PNS
Connections are required between PNS and CNS, but PNS can act autonomously in some cases
Invertebrates lack myelin but action potential propagation overcome by increasing diameter of axons
What do all vertebrate nervous systems contain?
- Sophisticated sensory mechanisms
- Clear differentiation of the CNS and PNS as well as sensory and motor nerves
- Elaboration of brain structure
All contain:
- Forebrain (cerebrum, optic structures, olfactory lobe)
- Midbrain
- Hindbrain (brainstem (pons, medulla) cerebellum)
What is the sulci?
Infoldings of the cerebral hemispheres that form ‘valleys’ between the gyri
What is the gyri?
Ridges of the infolded cerebral cortex
What are the lobes of the human brain?
- Frontal lobe
- Parietal lobe
- Occipital lobe
- Temporal lobe
- Limbic lobe
- Corpus callosum
What are the two subdivisions of the PNS?
Afferent Sensory Division
- Information coming into the body and CNS
Efferent Motor Divison
- Information from the CNS to muscles, glands, etc…
What are the two subdivisions of the Efferent Motor Division of the PNS?
Visceral/Autonomic Motor Division
- Autonomic Nervous System, Parasympathetic and Sympathetic
Somatic Motor Division
- Voluntary
Structure of the forebrain, midbrain and hindbrain?
Forebrain (prosencephalon) consists of:
- Telecephalon (cerebrum)
- Diencephalon (thalamus and hypothalamus)
Midbrain (mesencephalon)
Hindbrain (rhombencephalon) consists of:
- Myelencephalon (medulla)
- Metencephalon (pons and cerebellum)
What are the divisons of the brain?
Cerebrum
Diencephalon
Brain stem
Cerebellum
What are the functional regions of the brain?
Motor:
- Primary motor and premotor in frontal lobe
Sensory:
- Primary somatosensory and somatosensory association areas in parietal lobe
Vision:
- Primary visual and visual association areas are in occipital lobe
Auditory:
- Primary auditory and auditory association areas in temporal lobe
What are the 7 major parts of the CNS?
BRAIN DIVISIONS:
Cerebrum
Diencephalon
Brain Stem
- Midbrain
- Pons
- Medulla
Cerebellum
Spinal Cord
What is white matter and grey matter?
Cell bodies of neurons reside in the gray matter. It has a pinkish/grey colour in the brain, and is a major component of the CNS
Myelinated Axons reside in white matter. These axons connect different parts of the grey matter to each other
Grey matter resides on the outside of the brain, white matter resides on the inside
What are the 3 brain planes?
Coronal
Sagittal
Horizontal/Axial
What are the directions of the head in a forward looking head
Anterior = front
Posterior = back
Ventral = front
Dorsal = back
Superior = top
Inferior = bottom
Rostral = head end
Caudal = tail end (spinal cord)
What protects the CNS?
Bone:
- Skull
- Vertebral column
Meninges
Cerebrospinal fluid
What are meninges?
Meninges enclose the brain and spinal cord and their blood vessels
They are formed from 3 protective tissue layers:
- dura: superficial most and strongest, usually in contact with bone
- Arachnoid: adhered closely to dura, web-like in appearance
- Pia: deepest layer, in direct contact with CNS tissue
What is cerebrospinal fluid? (CSF)
It is a clear, cell free fluid produced by the choroid plexus (ependymal cells) that circulate in the subarachnoid space (the space between the arachnoid and pia mater)
How do the cerebral hemispheres receive input?
Afferent input goes into the somatosensory cortex (located in the neocortex, more specifically in the parietal lobe) and comes from a variety of areas:
- Large portion is ascending information from the thalamus
- Ascending information from the brainstem and other parts of the forebrain, also the hypothalamus
- Axons travelling between hemispheres (commissural fibres)
- Information from the ipsilateral cortex
How do the cerebral hemispheres give output?
Output from the neocortex is always excitatory from pyramidal cells (uses excitatory neurotransmitters such as glutamate, etc)
- All parts of cortex project to thalamus
- Axons from motor & somatosensory cortices project to basal ganglia
- Axons project to brainstem (nuclei) and spinal cord
- Axons project to contralateral hemisphere; axons project to ipsilateral hemisphere
What is the brains stems function?
Serves as a conduit for ascending & descending tracts connecting the spinal cord to higher centres (cerebrum, cerebellum)
Contains important reflex centres associated with control of respiration, heart rate & blood pressure, and consciousness
Contains cranial nerve nuclei
What are the functions of the cerebellum?
- Integrates ascending (proprioceptive) information, feeds back to cerebral cortex to refine movement
- Modifies movement (compares sensory information with pre-motor information)
Maintenance of upright posture
Maintenance of the tension or firmness (i.e., tone) of the muscle.
Aids the cerebral cortex in planning sequential movements to make smooth progressions from one movement to the next
Synergy of Movement – Motor coordination
Balance
What routes does cerebellar input come from?
- Spinal cord
- Cerebellar cortex
- Vestibular system
- Motor systems in neocortex
What routes does cerebellar output take?
- Vestibular systems
- Brain stem
- Muscle spindles
- Motor and pre-motor cortices
What is the spinal cord?
It is a two-way impulse conduction pathway and reflex centre
It contains 31 pairs of spinal nerves in total:
- 8 cervical nerves (C1 – C8)
- 12 thoracic nerves (T1 – T12)
- 5 lumbar (L1 – L5)
- 5 sacral (S1 –S5)
- 1 coccygeal (Co)
These nerves give rise to the peripheral nerves of the body
Spinal nerve afferent information route
Each spinal nerve has a:
- Dorsal root (posterior) through which afferent fibres enter, and which contains the dorsal root ganglion* (DRG) with the cell bodies of the afferent fibres
Spinal nerve efferent information route
Each spinal nerve has a:
- Ventral (anterior) root through which the efferent fibres leave. Their cell bodies are within the spinal cord
What are reflexes?
Survival mechanism
Inherited (‘hard-wired’), pre-set behaviour that does not require learning, practice, or experience
Simplest type of animal behaviour
Performed without conscious thought; usually rapid, automatic/ involuntary responses to stimuli.
Usually follow specific pattern
What is a reflex arc and what is the structure?
The nerve pathway involved in a reflex action, including at its simplest a sensory nerve and a motor nerve with a synapse between
Reflex arc structure =
- Receptor (site of stimulus)
- Sensory neuron (transmits stimulus)
- Integration centre (can be mono or polysynaptic)
- Motor neuron (conducts impulse to effector)
- Effector (muscle or gland)
What are polysynaptic reflexes?
Reflex that involves multiple synapses between sensory axons, interneurons, and motor neurons
Interneurons control more than 1 muscle group
Produce either EPSPs or IPSPs
Example: withdrawal reflex from hot pan
What is the autonomic nervous system?
The autonomic nervous system is a component of the peripheral nervous system that regulates involuntary physiologic processes including heart rate, blood pressure, respiration, digestion, and sexual arousal
Contains 2 divisions responsible for the maintenance of homeostasis
Both systems are continuously active under normal conditions, with each having discreet and independent functions (antagonistic functions!)
ANS together with the endocrine system controls the body’s internal organs, thus controlling the circulation of blood, activity of the gastrointestinal tract and body temperature.
Innervates smooth muscle, cardiac muscle and glands of internal organs (Involuntary!)
Neuronal structure and signal summation?
Dendrites receive information from adjacent axons
Axons send information from one end of the neuron to other (faster if myelinated)
Oligodendrocytes provide myelination in the CNS and Schwann cells provide myelination in the PNS
Signals from the cell soma are summated at the axon hillock. The hillock is considered the ‘trigger zone’ which must reach threshold potential to achieve an action potential
Both the hillock and axon initial segment (AIS) are rich in voltage-gated Na+ channels.
Myelin begins after the AIS
What proteins can be used to identify dendrites and axons in a neuron?
MAP2 (Microtubule Associated Protein) is a neuron-specific cytoskeletal protein found in dendrites
Beta-IV Spectrin is a cytoskeletal protein found in axons as well as some non-neuronal cells
What are the 3 types of neurons?
3 types of neurons:
-Motor neurons
- Relay commands from brain and spinal cord to muscles and glands
-Sensory neurons
- Transmit information from sensory receptors to the brain and spinal cord
-Interneurons
- Process and integrate information within the brain and spinal cord, facilitating communication between sensory and motor neurons
What is golgi stain?
Golgi stain:
- Nervous tissue treated with potassium dichromate and silver nitrate results in silver precipitation (from silver chromate) inside the neurons
Allows us to see details of dendrites such as dendrite spines
What is nissl substance and how is it visualised?
Nissl bodies (or Nissl substance) are large granular structures found within neurons
They consist mainly of rough endoplasmic reticulum and polyribosomes, making them key sites for protein synthesis within the neuron
The presence of Nissl substance can be visualized using Nissl staining, which targets these regions specifically.
Dendrites have a small amount of nissl substance
Axons have no nissl substance as no protein synthesis occurs here
What are the 2 types of sensory neurons?
Pseudounipolar neuron
1 branch (dendritic becomes axonal)
(commonly found in dorsal route ganglia)
Bipolar neuron
2 branches (separate dendritic and axonal branches)
(commonly found in olfactory system)
Spinal ganglia structure?
Ganglia are aggregations of nerve cells (ganglion cells) outside of the CNS
Dorsal root ganglia are surrounded by a connective tissue capsule, which is continuous with the peripheral nerve
Individual ganglion cells are surrounded by a layer of flattened satellite (fibroblast) cells.
What are satellite cells?
Located in the Peripheral Nervous System (PNS)
Encircle and closely envelop neuron cell bodies in ganglia
Provide structural support, regulate the microenvironment around the neuron, and potentially play a role in neuronal homeostasis and repair
What are interneurons?
Location: Primarily within the Central Nervous System (CNS)
Description: Neurons that connect and relay signals between sensory neurons and motor neurons
Function: Process, integrate, and modulate information within neural pathways, contributing to reflexes, relaying information, and complex processing tasks
What are pyramidal neurones?
- Located in the cerebral cortex and hippocampus
- Large, pyramid-shaped cell body with a single, long apical dendrite and several basal dendrites
- Principal excitatory neurons in the cortex, involved in motor control and cognitive functions.
What are purkinje cells?
- Located in the cerebellar cortex.
- Large, elaborately branching dendritic tree
- Principal neurons of the cerebellar cortex, inhibitory output to the deep cerebellar nuclei, playing a critical role in motor coordination
What are the layers of the cerebral cortex and what cells are contained within them?
Cerebral cortex is composed of grey matter
Six Layers of the Cerebral Cortex:
Layer I (Molecular Layer):
- Contains very few neurons; mainly consists of the apical dendrites of pyramidal cells and axons from other layers.
Layer II (External Granular Layer):
- Similar to layer I
Layer III (External Pyramidal Layer):
- Contains small-sized pyramidal neurons
Layer IV (Internal Granular Layer):
- Mainly consists of granular cells
Layer V (Internal Pyramidal Layer):
- Contains large pyramidal neurons
- Gives us motor output the drives voluntary muscular movement
Layer VI (Polymorphic or Multiform Layer):
Cytoarchitecture of the cerebellar cortex?
- Three layers within the grey matter with a variety of cell types
- Myelinated fibres in the white matter (deep to gray matter)
3 layers are:
- Outer Molecular layer
- Single layer of Purkinje cells
- Granular cell layer
What are the three layers of the cerebellar cortex?
Molecular layer (outermost layer):
- Basket cells,
- Stellate cells
Purkinje Layer:
- Purkinje cells
Granule cell layer (innermost layer):
- Granule cells (most abundant neuron in brain)
- Golgi cells
What is the blood brain barrier?
A barrier composed of endothelial cells joined by tight junctions
Forms glial-limiting membrane around blood vessels and along CNS surface (as part of the blood brain barrier)
Prevents diffusion of solutes and fluid into brain and spinal cord
O2, CO2, lipid soluble molecules (hormones)
> 500 daltons MW not permissible
Integrity highly dependent on astrocyte ‘end feet’
What is the difference in ion concentration between the inside and outside of the axon?
What happens when permeability changes?
Sodium ions will enter (inwards sodium current) (depolarisation)
Potassium ions will leave (through potassium leak channels)
What is the nernst equation and what is it used for?
Comparing two gradients
To determine the direction of ion movement at any given membrane potential
In effect, this converts chemical gradient to an electrical gradient
What version of the Nernst equation will we use?
at 37 degrees (for mammalian neurone)
For an invertebrate, squid rt/zf is 58
What is the goldman constant field equation?
Essentially an extended version of the nernst equation
P represents the permeability of its related ion
How do voltage gated sodium channels work?
Diagram of action potential sequence
What happens at the start of neurogenesis?
At 18 days of development, after formation of endoderm, mesoderm and ectoderm, the formation of the notochord at the midline occurs
The notochord instructs the development of the neural plate, which develops from overlying ectoderm (neuroectoderm)
Neural plate contains a lot of cells called ‘Neuroectodermal precursor cells’, which play an important role in neurolation
This will give rise to the entire nervous system
Formation of the neural groove?
As the neural plate differentiates, it folds inwards and begins to create a neural groove
At the top of the groove, a neural crest begins to form
Formation of the neural tube
The neural plate continues to fold, and the neural folds at the top are fused together generating a neural tube
Some cells from the tube migrate to form neural crest
Neural crest gives rise to sensory nervous system
Floorplate is located above notochord
Where the tube has closed, is called the roofplate
What are transient structures in neurolation?
These are temporary structures that play vital roles during the early development of the nervous system
Notochord:
- A rod-shaped structure that forms the primitive axial skeleton.
- It releases signals that influence the development of surrounding tissues, particularly the neural tube
Floorplate:
- Located on the ventral (front) side of the developing neural tube
- It’s involved in the ventral patterning of the neural tube and influences the differentiation of motor neurons
Roofplate:
- Situated on the dorsal (back) side of the neural tube
- It’s involved in the dorsal patterning of the neural tube and influences the development of sensory neurons
Somites:
- Secrete morphagens
What are hox genes?
Family of transcription factors
Establish segmentation along anterior- posterior axis
What are the key steps and outcomes of neuroblast migration in cortex formation?
Neuroblasts migrate towards the pial surface
Here, they form the marginal zone
These migrating cells differentiate into neurons
Newer neuroblasts migrate past older ones, meaning the cortex is built in an “inside out” fashion
A neuron’s final position in the cortex indicates its birthdate
This leads to a columnar organisation of the cortex
How do axons navigate
Axons navigate via intermediate targets
Axons grow along other axons as guides
What are growth cones?
Described by Cajal, 1890 as motile structure
At the tip of growing axons and dendrites
Hand-like structures with receptors on the surface
Senses guidance cues
Overview of axon innervation during development
What happens when growth cones reach the target?
Neurones make a number of connections with target cells
Initially, surplus connections are made
Connections are then refined, so the neurone innervates the correct number of target cells and the target cells are innervated by the correct number of neurones
Are all contacts between axons and target kept?
Some synapses are kept, other abandoned
Neurotrophins and electrical activity determine final pattern of contacts
What is developmental cell death?
Victor Hamburger discovered that limb removal results in reduced numbers of motor and sensory neurons in the chick spinal cord (1934)
Central dogma nerve regulation
How is GABA synthesised?
Glutamate + Glutamic Acid Decarboxylase (GAD)
—-> GABA
GAD gene is recognised by transcription factors to ensure gene is selectively expressed in GABA neurons
GABA is the same structure as Glutamate minus 1 carboxyl group
Cytoskeletal elements compared?
Microtubules:
- 25nm diameter
- Made up of Alpha / Beta dimer subunits that build hollow tube
- Both subunits capable of binding GTP and GDP
- Microtubule has a negative (-) end and a positive (+) end
Actin filaments:
- 7nm diameter
- G-actin monomers make F-actin filaments
Intermediate filaments:
-10nm diameter
- Least dynamic
- Dimer, with a head and tail and a twisted helical structure in-between
Organization of the major cytoskeleton components within neurones
Actin cytoskeleton often associated in a cortical network enriched in terminal regions
Microtubules orientated unidirectionally in the axon compartment but bi-directionally in the dendrite. These make tracks for transport.
Neurofilament stabilizes axons
Polarity in axon is negative to positive (uni-directional)
Polarity in dendrites is both negative to positive and positive to negative (bi-directional)
What do kinesin and other motor proteins do?
Binds to Cargo or protein that needs to be transported
Binds to Microtubules
Uses ATP activity
Walk along the microtubule
Move protein to extremities of the processes where the major signalling happens
Kinesins move towards positive end
Dyneins move towards negative end
How do neurones communicate?
Processes with polarity (axon and dendrite)
Come close to each-other, potential to communicate
Using electrical communication to allow intercellular
communication
Using chemical communication to allow intercellular
communication
Sodium channel structure?
Sodium Channels made up of one protein sequence that contains 4 domains.
Each domain has a voltage sensor and ¼ of the pore.
Each domain is linked via intracellular loops
Each domain is made of 6 transmembrane helices
Intervening between #5 and #6 is a sequence called a re-enterant loop
Threshold for activation about -50 mV
Threshold for inactivation about 0 mv
Selective for Na+
What are the two ways of bridging the synaptic gap?
Electrical Synapse
- Signal passed direct electrical flow between two cells
Chemical Synapse.
- Electrical signal converted to a chemical signal and then back into an electrical signal
What are the types of synaptic sites and how do they produce inhibitory and excitatory responses in post synaptic neurones
Axo-dendritic synapse
- Axon –> dendrites
Axo-somatic synapse
- Axon –> cell body
Major excitatory synapse are on the dendrites and use glutamate as the transmitter
Major inhibitory synapses are on cell body and use
GABA or glycine as the transmitter
Glutamatergic vs GABA/Glycine synapse structures
They look different and are molecularly distinct.
Glutamatergic are often Asymmetric
- Vesicle called vesicle glutamate transporter
- Post synapse has thick specialization organizer proteins and cytoskeleton
- Post synaptic receptors are glutamate specific
- Flux of Na+/Ca2+ excites synapse
GABA/Glycine synapses are symmetric
- Vesicles called inhibitory amino acid vesicle transporter (IAAT)
- Post synapse has thin specialization organizer proteins and cytoskeleton
- Post synaptic receptors are glycine/GABA specific
- Flux of Cl- inhibits synapse
Key Features on excitatory and inhibitory receptors
Glutamate receptors
- Four subunits to make ion channel
- Glutamate binding site on outside
- Cation Channel
- Bind to molecules like PSD-95 on inside of postsynaptic cell.
Glycine receptors (GABA recpetors)
- Five Subunits to make ion channel
- Glycine binding site on outside
- Anion Channel
- Bind to Gephyrin on the inside postsynaptic cell
What are neurexins
Neurexins a family of presynaptic tags
Neuroligin 1 is a postsynaptic glutamatergic tag
Neuroligin 2 is a postsynaptic glycinergic tag
Neuroligins and neurexins
Neurexins (presynaptic) and neuroligins (postsynaptic) interact with each other at the synapse
Neuroligins interact with PSD95 (excitatory) or Gephryn (inhibitory) in the postsynaptic nerve to organise tags and receptors
Selective use of molecules can define synapse
- neuroligin 1, 3, 4 are excitatory
- neuroligin 2 is inhibitory
Make multiplex protein complex that are adhesive
and bring about signalling
molecular neuroscience disease examples
