Flashcards in Neuro Deck (134):
What is neuroanatomy?
The anatomy of the brain, spinal cord, peripheral and visceral nervous systems and sensory apparatus.
What does the nervous system control?
Multifunctional, integrated system that controls;
Movement and posture
Though - cognition, perception, attention, learning.
Emotions and behaviour
'Special' senses - sight, hearing, smell, taste, touch, proprioception.
Regulation of body systems - homeostasis.
What are the 7 major areas of functional clinical importance in the brain?
Cerebrum - cerebral cortex, white matter, basal nuclei
Diencephalon - thalamus, hypothalamus
Brainstem - midbrain, pons, medulla oblongata
Subcortical areas/basal ganglia
How do the major functional areas of the brain connect to allow operation as a system?
Via synapses between white and grey matter.
What are some parts of white matter?
Dendrites, Fibres, Axons, Connections
Tracts, Pathways, Peduncles
White colour comes from myelin.
What are some parts of grey matter?
Cell bodies, neurons
(Cell to cell connections - cell bodies)
What are the cellular building blocks of the nervous system?
Neurons - sensory, interneurons or efferent
What factors govern the % of white versus grey matter?
Depth, area, thickness, length and density all alter.
What comprises the peripheral nervous system?
Motor (somatic, visceral) and sensory systems (somatic, visceral, proprioception).
All Afferent - to CNS
What comprises the CNS?
All efferent - away from CNS.
What is the function of the cerebral cortex?
Highest level of neural processing.
Has discrete functional areas - motor, auditory, visual and somatosensory cortexes.
Learning, memory, emotion.
(L) brain - (R) side movements and sensation, creativity, music, dream interpretation, imagery, spatial orientation.
(R) brain - (L) side movement and sensation, logic, analytical processing, strong language capabilities, maths, philosophy, intuition.
Describe the cerebral cortex.
6 layered structure created in inside to outside manner.
Specific regionalisation of motor and sensory input.
Higher coordination of motor output.
What are the two components of the basal ganglia?
Describe the sub-cortical nuclei and tracts.
Regulates movement (smoothness and development of motor strategies) - feedback to cortex via thalamus (inhibitory).
Clinical significance - parkinson's disease (loss of communication between BG and cortex).
What is the function of the midbrain?
Poorly understood in animals - humans it suppresses unwanted movements and enables smooth switching between commands that initial and terminate movement.
No direct connection to either lower motor neurons so influence is via upper motor neurons.
What is the most important component of the midbrain?
What are the components of the limbic system?
Not a single region but a system of cortical/subcortical regions.
Why is the limbic system important?
Modulates emotion, fear, anxiety, memory.
What is the thalamus?
Collection of nuclei that form transit region for all sensory tracts.
Contains somatosensory nuclei, lateral geniculate nucleus (vision), and medial geniculate nucleus (auditory, visual reflexes).
What is the hypothalamus important for?
Behaviour - hunger, satiety, thirst.
Interacts with limbic system
ANS inputs (direct and indirect)
Circadian rhythm (pineal and suprachiasmic nucleus).
What does the brain stem contain?
Cranial nerve nuclei
Autonomic nervous system nuclei
Ascending reticular activating system (ARAS)
Connection to cerebellum
All descending and ascending pathways (tracts)
What are the functions of the cranial nerves?
Influence movement - feedback to LMNs to initiate and respond to changes in body/head position, mastication, eyelid and eyeball movement, facial expressions.
How do brain stem nuclei connect to the spinal cord?
Via extra pyramidal tracts (eg. reticular formation, vestibular nuclei, red nucleus).
What are the autonomic nuclei of the brain stem involved in the control of?
Edinger-westphal nucleus - pupillary constriction
Superior salivary nucleus - secretion of saliva and tears.
Inferior salivary nucleus - secretion of saliva, vasodilation
Nucleus ambiguus - PNS control of HR, larynx and pharynx.
Dorsal motor nucleus of vagus - PNS control of HR, bronchial constriction, peristalsis, secretion of digestive enzymes.
What is the reticular formation?
Network of nuclei/fibres that cross the hindbrain and midbrain region.
Rostral part of this is ARAS (sleep/wake).
Contains local somatic and cranial nerve nuclei for mastication, facial expression, reflex orofacial behaviours (sneezing, hiccup, yawn, swallow).
What is the spinal cord?
Connection between central and peripheral NS.
Connects ascending tracts to peripheral sensory nerves and descending tracts to motor neurons.
Describe spinal nerves?
Paired with dorsal (sensory) and ventral (motor) root.
Segmental arrangement - cell bodies of sensory component contained in spinal ganglia.
What is a myotome?
Muscle or muscle group innervated by one spinal nerve
What is a dermatome?
Area of skin innervated by one spinal nerve
What are the components of the Sensory peripheral NS (afferent)?
Somatic (changes to external environment) - general (GSA) CNV, all spinal nerves; specialised (SSA) CNII, CNVIII.
Visceral (changes to internal environment) - general (GVA) CNVII, CNIX, CNX, spinal nerves; specialised (SVA) CNVII, IX, X and I.
Proprioception - general (GP) spinal nerves, CNV; specialised (SP) CNVII.
What are the components of the Motor peripheral NS (efferent)?
Somatic (voluntary movement) - general (GSE) CNIII, IV, VI, XII, all spinal nerves.
Visceral (involuntary movement/regulation) - general (GVE) CNIII, VII, IX, I, XI; specialised (SVE) CHV, VII, IX, X, I.
What is sensory (afferent)?
Sensory, afferent, portion of PNS is classified on basis of location of dendritic zones in body.
What is somatic afferent?
Dendritic zone on/near surface of body, receives stimulation from the environment.
What is general somatic afferent?
Neurons distributed by the 5th CN to the surface of head, spinal nerves to surface of body and limbs.
Sensitive to touch, temperature, noxious stimuli.
What is special somatic afferent?
Dendritic zones of specialised sensory organs limited to one deep to surface of body but stimulated by change in external environment. (CNIII)
What is visceral afferent?
Dendritic zones in viscera, stimulated by changes in internal environment.
What is general visceral afferent?
CN VII, IX, X to visceral structures of head and by CNX and spinal nerves to visceral structures of body.
Includes blood vessels in trunk, limb and neck.
Stretch and chemical changes.
What is special somatic afferent?
Dendritic zones of CN VII, IX, and X that are limited to specialised receptors for taste and CNI whose dendritic zones respond to olfactory cues.
What is proprioception?
Dendritic zones responding to changes in position in limbs, body, head and neck.
What is general proprioceptive system?
Dendritic zones widely distributed in tissues of head, neck, trunk, limbs and joints deep to body surface.
Responsive to changes in length and position of innervated targets (muscles, tendons, ligaments).
What is special proprioceptive system?
Specialised receptors responding to position and movement of head. Located in portions of labyrinth of inner ear - signals via CNIII.
What are glial cells?
Non-neuronal cells of CNS.
Not neurons but they outnumber them 3:1
Critical for normal neuronal function - support and response cells. Don't participate in electrical signalling but regulate interstitial environment and help define synaptic contacts and maintain signalling abilities of neurons.
6 major types
What are the 6 major types of glial cells?
Peripheral NS - satellite, Schwann.
CNS - Oligodendrocytes, astrocytes, microglia, ependymal (not actual glial cell-very specialised neuroepithelial cell).
Which glial cells make myelin sheaths?
Schwann cells and oligodendrocytes.
What are the functions of glial cells?
Maintain ionic concentration in ISF (K+).
Modulate rate of nerve signal propagation (eg. myelin sheaths).
Influence synaptic transmission (neurotransmitter uptake).
Critical for normal neural development (radial glia).
Activated in recovery from neural injury (reactive gliosis, microglia).
Found in brain and spinal cord only.
Help maintain appropriate chemical environment for neuronal signalling - clean up debris, physical support, convert glucose to lactate (key energy source for neurons), contribute to BBB, control ECF K+ and Cl-, propagate normal neuronal cluster firing through connection to other glia via gap junctions.
Brain and spinal cord only.
Cellular processes wrap themselves around some axons - forms laminated, lipid rich sheath (myelin).
Processes go to several different axons.
Describe microglial cells.
Brain and spinal cord only.
Derived from haematopoietic precursor cells.
Function like tissue macrophages - primary scavengers, confer innate immunity within CNS, involved in neuronal remodelling, production of cytokines, growth factors.
Increased numbers at sites of injury, activated in states of disease or repair.
Secrete signalling molecules that can influence local inflammation and cell death/survival.
Self renewing population.
Describe ependymal cells.
Brain and spinal cord only.
Line ventricular cavities of CNS, help circulate cerebrospinal fluid (ciliated).
Absorptive and secretory in nature.
Modified tight junctions between these cells allows free fluid exchange between neuronal tissue and the blood capillary network.
What are schwann cells?
Peripheral NS only - analogous to oligodendrocytes in CNS.
Form myelin sheaths.
Phagocytotic activity - clear cellular debris.
Non-myelinating Schwann cells involved in maintenance of axons and crucial for neuronal survival.
Affected in demyelinating disorders.
Describe the difference in myelin sheaths between oligodendrocytes and schwann cells?
Oligodendrocytes sheath multiple cells on different axons.
Schwann cells sheath one axon but multiple cells along that axon.
Both affected by demyelinating disorders - MS, huntington's, alzheimers.
What is cerebrospinal fluid?
Clear watery fluid surrounding CNS and filling ventricular system within brain and spinal cord.
Similar to plasma - less glucose and proteins.
Secreted by ependymal cell of choroid plexus.
How many ventricles are there in the CNS? How are they connected?
2 lateral ventricles
3rd ventricle - under midbrain.
4th ventricle - under pons.
Central canal of spinal cord.
Connected by foramen
What are the functions of cerebrospinal fluid?
Interstitial fluid bathing neurons and glial cells - nutrient provision and removal of wastes.
Chemical buffer - maintains ionic concentration
Transport of neurotransmitters and other chemicals.
How is CSF produced?
By choroid plexus in lateral, 3rd and 4th ventricles.
Moves by subarachnoid system through apertures in each of the 4 ventricles.
What makes the CSF flow?
Pulsations of blood in choroid plexus.
How is CSF absorbed?
Mainly by arachnoid villi (granulations).
Passive diffusion into CSF and passive and active transport out of CSF.
What is the blood brain barrier?
Specialised capillary network surrounded by astrocyte processes.
Blocks large molecular weight molecules from passive diffusion.
It is not complete - some areas the BBB is 'leaky' (similar to normal capillary endothelium - hypothalamus and hippocampus). Allows brain to sample circulating substances such as hormones and respond accordingly.
How do and what molecules can cross the BBB?
Substances that can move freely across endothelial lining; gases and hydrophobic molecules diffuse freely, small lipophilic molecules, larger hydrophilic molecules (AA, CHO, ions) require specific transporters.
Water soluble molecules recognised by ATP dependent transport mechanisms can cross, some access by receptor mediated processes (insulin), others are unknown as to how they cross.
BBB also has pumps that actively pump molecules out of CNS circulation.
What is the channel that allow transport of molecules into or out of the CSF?
P-Glycoprotein (P-gp) - ATP dependent binding protein that prevents influx of complex molecules, also prevents retention of complex molecules by transporting them out of the CSF.
Key protein involved in drug resistance and CSF efflux of therapeutic drugs.
Can use blockers to facilitate maintenance of therapeutic agents in CSF.
What are the two types of synapse?
Chemical - most common
What are the stages of a typical chemical synapse?
1. Transmitter is synthesised and stored in vesicles.
2. AP invades presynaptic terminal.
3. Depolarisation of presynaptic terminal causes opening of voltage gated Ca channels.
4. Influx of Ca into synaptic cleft.
5. Ca causes vesicles to fuse with presynaptic membrane.
6. Transmitter released into synaptic cleft via exocytosis.
7. Transmitter binds to receptor molecules in postsynaptic membrane.
8. Opening or closing of postsynaptic channels.
9. Postsynaptic current causes excitatory or inhibitory postsynaptic potential that changes excitability of postsynaptic cell.
10. Retrieval of vesicular membrane from plasma membrane.
What is a neurotransmitter?
1. Must be present within presynaptic neuron.
2. Must be released in response to presynaptic depolarisation.
3. Release is usually Ca dependent.
4. Specific receptor must be present on post synaptic cell.
Describe how neurotransmitters can have duality of action?
Post synaptic receptors can be excitatory or inhibitory.
What are the mechanisms of post synaptic excitation?
1. Opening of Na channels.
2. Depression of Cl- and K+ channels (EPSP).
3. Increase in number and localisation of excitatory post synaptic receipts or suppression of inhibitory receptors.
What are the mechanisms of post synaptic inhibition?
1. Opening of Cl- channels.
2. Enhanced transport through K+ channels (creates inhibitory post synaptic potential IPSP).
3. Increase in number and localisation of inhibitory post synaptic receptors or inhibition of cellular metabolism.
What are the different forms of neurotransmitters?
Small molecule NT's - synthesised within nerve terminal, mediate rapid synaptic action (ACh, Ad, AA, purines, histamine).
Neuropeptides - synthesised in cell body, slower ongoing synaptic function (vasopressin, oxytocin).
Unconventional NT's - eg. NO, endocannabinoids.
True or false. There is more than one synapse per cell?
True or false. There is more than one NT per synapse.
True or false. There is more than one receptor per synapse?
Which NT's are released at low frequency?
Which NT's are released at high frequency?
Small NT's, large NT's and neuropeptides.
What are the two types of NT receptors?
Ionotropic - ligand gated ion channels.
Metabotropic - G-protein coupled receptors.
How do ionotropic receptors work?
1. NT binds to outside surface.
2. Channel opens.
3. Ions flow across membrane.
Physical change to receptor.
How do metabotropic receptors work?
1. NT binds.
2. G-protein is activated.
3. G-protein subunits or intracellular messengers modulate ion channels.
4. Ion channel opens.
5. Ions flow across membrane.
Describe it the inotropic receptor for ACh.
Ionotropic - nicotinic receptors (nAChR).
Has 5 protein subunits - 3 alpha, 2 beta typically.
Have diffuse, presynaptic location in CNS.
In post synaptic membrane of peripheral NS.
Describe the metabotropic receptor for ACh.
7 subunits and 5 subtypes (M1-5)
Highly expressed in forebrain regions - ACh stimulation activates K channels.
Hippocampus - excitation causes closure of K channels.
Ganglia of peripheral NS.
Mediate cholinergic response of heart, smooth muscle and exocrine glands - reduction of HR via vagal nerve.
What role does glutamate play?
Most excitatory neurons use this as their NT.
Doesnt cross BBB - synthesised locally in mitochondria by recycling/reuptake.
Excitatory AA transporters (EAAT) on membrane of glial cells and neurons - remove glutamate from synaptic cleft, mediate delivery and uptake of glutamine from glial cells to neurons.
In neurons - glutamate loaded into vesicles by VGLUT.
What is EAAT?
Excitatory AA transporter.
What is an NMDA receptor?
N-methyl-D-aspartate receptor for glutamate.
How many classes of metabotropic glutamate receptors are there? Are they all excitatory?
No, both inhibitory also.
Using your knowledge of NT modulation at the synapse, will a NT reuptake inhibitor increase post synaptic receptor activation?
Yes - due to increase in NT available at synaptic cleft.
What is GABA?
Present in inhibitory synapses in brain - particularly in local circuit interneurons and cerebellum.
How is GABA synthesised and how is it removed from the synaptic cleft?
Synthesised from glutamate.
Removed by specific transporters - GAT.
What are the different types of GABA receptors?
3 types - all inhibitory.
GABAa, GABAc ionotropic - permeable to Cl which inhibits postsynaptic cells. Have 2 binding sites for GABA.
GABAb metabotropic - mediated inhibition due to activation of K channels OR blockage of Ca channels (causing hyper polarisation of postsynaptic cells).
Where will you find glycine? How is it placed in vesicles?
More localised to spinal cord than GABA.
It is a serine derivative that is placed into vesicles via VIATT.
What is the smallest NT? Discuss it.
Small molecule NT, diffuses rapidly across membranes and between cells (not limited to synapses), fast acting (very short duration), produced by nitric oxide synthase (NOS) and there are cell specific versions (eg. neuronal NOS - nNOS).
Spontaneously oxidises and regulates synapses that also employ conventional NT's.
Withdrawal from GABA agonists, administration of GABA agonists and hypo magnesia can all cause seizures. What is the common link between these three states at a synaptic level?
Decreased activation of inhibitory post synaptic receptors.
What are the stages of dopaminergic neurotransmission?
1. Dopamine loaded into vesicles by vesicular monamine transporter (VMAT).
2. Reuptake via Na dependent dopamine transporter (DAT) that terminates synaptic action.
3. Dopamine acts exclusively by activating G-protein coupled receptors (metabotropic).
4. Excess dopamine converted to deaminated metabolites by monoamine oxidase (MAO) present both pre and post synaptically (in mitochondria).
What receptors do Ad and NAd require?
Alpha and beta adrenergic receptors (G-protein coupled).
Ad mainly in peripheral NS, some in lateral tegmental neurons.
NAd from locus coeruleus.
Where is serotonin mainly found?
Primarily in neurons of pons and upper brainstem.
Widespread projections to forebrain and cerebellum.
Regulates sleep and wakefulness..
From neurons in hypothalamus.
Sparse projections to almost all regions of brain and spinal cord - mediates arousal and attention, controls reactivity.
Receptors are all g-protein linked.
All synaptic vesicles contain ATP which is released as cotransmitter with classical NT.
3 receptor types - 2 g-protein linked, 1 ionotropic.
Excitatory in motor neurons of spinal cord, sensory and ANS ganglia.
What are neuropeptides? What are their different forms?
Pre-propeptide - synthesised in neuronal cell body within RER.
Propeptide - transverse to golgi apparatus where it is packed into vesicles.
Active peptide - produced by proteolytic cleavage, modification of peptides, glycosylation, phosphorylation and disulphide bond formation within vesicles.
True or false, pro peptides can give rise to more than one peptide NT?
True or false, more than one NP can be released from a single vesicle?
Name some peptides in terms of their location within the body.
'Brain-gut' peptides - CCK-8, vasoactive intestinal peptide (VIP), substance P.
Opioid peptides - enkephalins, endorphins.
Pituitary peptides - vasopressin, oxytocin, ACH.
Hypothalamic releasing peptides - TRH, LH, somatostatin.
Miscallaneous - angiotensin II
What are some diseases that may affect the presynaptic terminal?
Clostridium toxicity (botulism, tetanus)
Affect exocytosis or endocytosis of presynaptic vesicles.
What affect do anaesthetic agents have and how do they do this?
Prevent awareness of sensory input and subsequent recall of sensory events after administration, altered consciousness.
Do this through interference of NMDA receptor mediated post synaptic activation or stimulation of GABA receptors.
Eg. Diazepam, ketamine, thiopentone.
What do ACh, glycine and GABA all have in common in terms of receptor binding sites?
Can be located within plane of membrane - within ion channel lumen or on outer side of alpha-helix lining the lumen.
These sites act to inhibit transmission/frequency/duration of post-synaptic potentials thus reducing synaptic activation inhibiting neuronal activity.
Multiple binding sites give capacity for multiple anaesthetic application.
Why are GABA receptors so important?
They are the most clinically important drug binding sites for benzodiazepines (tranquillisers - control seizure activity) and barbiturates (hypnotics - control epilepsy).
What is excitotoxic neuronal cell death?
Inducement of neuronal cell death by excessive glutR activation.
Damage to postsynaptic neurons.
Glutamate receptors antagonists effective at reducing exitotoxic cell death.
What is sleep?
The normal suspension of consciousness.
Electrophysically defined by specific brain wave criteria - measured on EEG.
Occurs in daily 'circadian' rhythm.
Predatory animals sleep the longest.
Necessary for life - deprivation results in compromised immunity, diminished cognitive function/mood swings/hallucinations/seizures, alterations in temperature regulation and food intake, death.
Why do we sleep?
Repletion of cellular energy stores - metabolic theory (particularly brain glycogen).
Energy conservation and tissue repair.
Memory processing (learning)
How is sleep regulated?
Brainstem - melanopsin containing cells in retinal ganglion cell layer respond to ambient light (mediates circadian activity and communicates with pineal gland for synthesis and secretion of melatonin).
Other sleep inducing substances include IL-1, interferon, serotonin and TNF.
What is active during non-REM sleep?
Brain is inactive.
What is active during REM sleep?
Inactive body - increased GABAergic activity in pontine reticular formation which interacts with LMN's in spinal cord (inhibited motor and sensory activity).
What inhibits somatosensory stimulation during sleep?
Inhibition from pons to dorsal column nuclei, decreased response to somatic sensory stimuli and inhibition of LMN's causes paralysis.
How do we stay awake?
Stimulation of cholinergic neurons of ARAS induce wakefulness from sleep.
What does stimulation of the thalamus cause in terms of sleep?
Causes an awake animal to fall asleep
What is the ARAS?
Ascending reticular activating system
One branch projects through lateral hypothalamus to cerebral cortex - includes monoaminergic network (biogenic amines).
Second branch projects to thalamus - histaminergic neurons, cholinergic neurons (wakefulness when activated).
What are the 3 main NT's involved in sleep?
ACh, NAd, Serotonin.
What does EEG stand for?
What does an EEG do?
Measures brain activity - electrical activity between 2 electrodes applied to scalp.
Location of electrodes determines areas that will be measured.
Poor spatial resolution - can only localise to within a few cm.
Activity in different areas corresponds to activity of populations of neurons.
What is an EEG trace?
Summation of neuronal activation between the electrodes.
What is the awake state characterised by on an EEG?
Low summation and small amplitude due to higher activity and asynchronous firing.
What is the sleep state characterised by on an EEG?
High summation and larger amplitude due to lower activity with synchronous firing.
Delta waves of deep sleep.
What are the 4 basic recording patterns of EEG's?
Alpha - 8-13Hz frequency, amplitude 10-50mV - awake with eyes closed (resting).
Beta - 14-60Hz frequency, lower amplitude <10mV - mental activity and attention.
Theta - 4-7Hz, higher amplitude - drowsiness, sleep (stages 1, 2).
Delta - <4Hz, variable amplitude - sleep (stages 3 and 4), pathological state.
What does REM sleep look like on an EEG?
Looks like beta waves - follows theta waves generally on incline back up from delta.
What are the characteristics of stage 1 sleep?
What are the characteristics of stage 2 sleep?
Non-REM (light sleep)
Larger amplitude waves called sleep spindles - last only a few seconds.
What are the characteristics of stage 3 sleep?
Non-REM (moderate to deep sleep)
Increasing amplitude, 50-150mV
Decreased number of spindles.
Delta waves (slow wave sleep)
What are the characteristics of stage 4 sleep?
non-REM (deep sleep)
0.5-4Hz (very low frequency)
Increasing amplitude, 100-200mV
Delta waves (slow wave sleep)
Does the brain cycle through the stages of sleep?
Yes, 1 through to 4 then back to 1, REM occurs for @ 10minutes then cycle begins again.
What are the 4 stages of sleep characterised by in terms of the body?
Decreased muscle tone, body movements, HR and RR, metabolism and temp.
Lowest during stage 4.
What movements occur during REM sleep?
Rapid eye movement
Paralysis of many large muscle groups.
Does dreaming correspond to appropriate sensory stimulation?
When does sleep walking occur?
Stage 2-3 sleep.
How are REM and awake different?
During REM sleep there is increased activity in GABAergic neurons in pontine reticular formation (inhibits LMN in spinal cord) preventing motor activity, there is also increased activity of descending inhibitory projections from pons to dorsal columns (inhibits sensory/mechanosensory stimulus).
REM sleep is due to activity of cholinergic neurons of ARAS however serotonin and NE neurons are inactive.
Is dreaming limited to REM sleep?
What are the differences between slow wave and REM sleep?
Slow wave - slow, medium to high amplitude, moderate muscle tone and some movement, decreased HR and RR, logical unspecific dreams, little eye movement, forebrain is site of induction for CNS, essential to survive.
REM - fast, low amplitude, little muscle tone and no movement (except twitches), increased HR and RR, vivid and illogical dreams, frequent rapid eye movement, pons is site of induction for CNS, not essential for survival.
What are some disorders of consciousness and sleep?
Narcolepsy (sleep attacks)/cataplexy/insomnia
What occurs during a seizure?
Normal brain activity requires asynchronous firing however during seizure, areas of brain activate synchronously (large numbers of neurons firing at same time).
Fine graduation of control are lost - loss of motor control, coordination, sensation, smell, consciousness.