2.2 Neurotransmission + 2.3 Organisation of the cerebral cortex Flashcards
Neurotransmission is restricted to specialised structures around the synapse including:
- Presynaptic nerve endings/terminals (each neurone has hundreds to thousands)
- Synaptic cleft (20 – 100 nm) represents ____________ (must be overcome using chemical neurotransmitters)
- Postsynaptic regions (usually dendrites or soma)
high electrical resistance
There is a wide variety of neurotransmitters and the genes encoding their receptors:
• Mediate rapid (μs – ms) or slower (ms – s) effects, and vary in abundance from mM to nM (usually __________)
• Neurones receive multiple transmitter influences which are integrated to produce diverse functional responses
- Amino acids: Mediate fast synaptic events (both excitatory and inhibitory):
• __________: potent excitatory transmitter (for most fast actions)
• ______________: most inhibitory transmissions
- Amines: Noradrenaline, dopamine, acetylcholine
- Neuropeptides: __________
neuropeptides;
Glutamate;
γ-aminobutyric acid (GABA);
Opioids
The mechanism of release of neurotransmitters is common to all the different types:
• Synapse consists of the presynaptic knob which contains ____________
• Wave of depolarisation allows the influx of ________, which is required for the release of neurotransmitters into the synaptic cleft
• Neurotransmitters then bind to postsynaptic membrane, leading to an influx of ______, allowing for depolarisation of the postsynaptic cell
• Transporter molecules uptake the transmitters back into the _________ to prevent overstimulation of the receptors
synaptic vesicles;
Ca2+;
Na+;
cytosol
The essential components of synaptic transmission includes the following:
• Restricted to _________ (synapse)
• Capable of a fast response (within 200 μs)
• Calcium is essential (transmitter release requires increased intracellular Ca2+ - 200 μM)
• Synaptic vesicles are source of __________ (4000–10000 molecules per vesicle)
specialised structures;
neurotransmitters
SYNAPTIC VESICLES
The synaptic vesicles (contains neurotransmitters) are associated with the presynaptic part of the synapse (immediately opposite the postsynaptic region full of receptors):
• Interaction between synaptic vesicle proteins and the presynaptic membrane proteins forms a stable complex (occurring in _____________ → forms super helix)
• __________________ in the presynaptic vesicles prepares them for release when the wave of depolarisation arrives
• Interaction with Ca2+ via the ______________ results in a conformational change, allowing the vesicle to open and release the neurotransmitter
The process of transmitter release requires the following processes to occur:
- Transmitter-containing vesicle docked on presynaptic membrane
- Protein complex formation between _____, ________, ________ to enable vesicle docking and rapid enable vesicle docking and rapid response to Ca2+ (membrane fusion and exocytosis) 3. ATP and vesicle recycling
α-helical domains;
Orderly docking of vesicles;
Ca2+ sensor protein ;
vesicle, membrane, cytoplasmic proteins
What is the effect of Zn2+-dependent endopeptidases?
Inhibits transmitter release
What is the effect of α-latrotoxin?
From black widow spider; stimulates transmitter release until depletion
What is the effect of Tetanus toxin?
From Clostridium tetani; causes paralysis
What is the effect of Botulinum toxin?
From Clostridium botulinum; causes flaccid paralysis
Ion channel receptors
- typically __________
- Binding causes ______________ which opens the channel (entry of Na+)
- Mediate all fast excitatory and inhibitory neural transmission
- CNS: ___, ______
- NMJ: ____________
pentameric;
conformational change;
glutamate, GABA;
ACh (at nicotinic receptors)
G-protein coupled receptors
- Contains ________________
- Binding activates _____________ to bind GTP, activating effector (e.g. adenylyl cyclase)
- Mediates production of second messenger (e.g. cAMP) leading to signal amplification
- PNS: ACh (at _____________), dopamine, noradrenaline, 5-hydroxytryptamine (5HT), neuropeptides (e.g. _________)
7 transmembrane α-helices;
G protein;
muscarinic receptors;
enkephalin
Excitatory ionotropic receptors
- Influx of Na+: ______, ______
- Membrane potential - less negative → excitatory postsynaptic potential (EPSP)
Nicotinic acetylcholine receptor (nAChR), Glutamate receptor (GLUR
Inhibitory ionotropic receptors
- Influx of Cl-: __________. ________
- Efflux of K+:____________
- Membrane potential - more negative → inhibitory postsynaptic potential (IPSP)
GABA receptor (GABAR), glycine receptor (GlyR);
5HT3 receptor (amine receptor)
Glutamate receptors (two types) mediate excitatory postsynaptic potentials:
AMPA receptors
- Most GLUR; mediate __________________
- Allow influx of _____
NMDA receptors
- Coincidence detectors (require cells to be ______________); mediate slow excitatory postsynaptic potentials
- Allow influx of ________________
Glutamate is formed from the ____________, and is abundantly produced in the synapse and released upon depolarisation into the synapse to interact with receptors:
• Receptor which it interacts with depends on whether the cell has been previously depolarised (either AMPA gating Na+ alone or NMDA gating Na+ and Ca2+)
• Glutamate then dissociates from GLUR (mainly inactivated via uptake into glial (e.g. astrocytes) and neuronal cells mediated by __________________)
• Glutamine synthetase (abundant in glial cells) converts glutamate into _______, which has no effect on neuronal conductance
fast excitatory postsynaptic potentials;
Na+;
previously depolarised;
Na+ and Ca2+;
Krebs cycle;
excitatory amino acid transport (EAAT);
glutamine
Seizures: abnormal cell firing may lead to seizures associated with ________________ in the synapse
• Glutamatergic mechanisms result in excitotoxic damage (aberrant neuronal excitability)
excess glutamate
The inhibitory CNS synapse is mediated by GABA (produced from glutamate via a __________________):
• Depolarisation of the terminal leads to vesicular release of GABA, which binds to its receptors, resulting in opening and influx of _______
• Rapid inactivation of GABA is mediated by _________________ (present on glial cells and neuronal cells), then by GABA transaminase (GABA-T) to form ____________) which can be fed back into the Krebs cycle:
• GABA is used to fill empty synaptic vesicles if taken up by neuronal cells
The GABA receptor possesses a ________________ (with multiple pharmacologically important binding domains):
• Barbiturates and benzodiazepines (e.g. diazepam) target different domains to modulate the activity of GABA (enhancing inhibitory effects)
• Widely used as antiepileptics, anxiolytics (treat anxiety), sedatives, muscle relaxants
single decarboxylation reaction;
Cl-;
GABA transporter (GAT);
succinic semialdehyde (SSA);
pentameric organisation
What is the action of barbiturates?
Increase frequency of channel opening
What is the action of benzodiazepines?
Increases open time of the receptor
The grey matter of the cerebral cortex is organised into 6 layers (arranged in columns), with the 1st layer at outer edge (pial surface) and the 6th layer adjacent to subcortical white matter:
• Each layer is differentiated by cell shape & connections
• Cortical columns are single functioning units of the cortex (cells within each layer forming connections with each other, and matching inputs and outputs)
What are the connections to each other?
1-3: Make intracortical connections (with other cells within the cortex) only:
• First 2 layers: make connections within same hemisphere
• 3rd layer: sends connections across the corpus callosum (bundle of white fibres interconnecting the 2 hemispheres)
4: Receive inputs from the thalamus (various thalamic nuclei)
5-6: Project axons out of the cortex to other parts of the CNS (e.g. corpus striatum, brainstem, spinal cord, thalamus)
What is the Corona radiata?
Top part of the internal capsule with fibres fanning out to all the different areas of grey matter
What is the corpus callosum?
Large commissure which fibres running across to interconnect the two cerebral hemispheres
What is the function of the association fibres (in white matter) and what are its examples?
Interconnects cells within the same hemisphere (short or long):
• Superior longitudinal fasciculus: quite long and interconnects cells in frontal lobe with those in parietal lobe and beyond
What is the function of the commissural fibres (in white matter) and what are its examples?
Interconnects cells between the two hemispheres:
• Corpus callosum: very large, interconnects virtually all areas
• Anterior commissure: much smaller, interconnects only certain structures in the medial part of temporal lobes
What is the function of the projection fibres (in white matter) and what are its examples?
internal capsule (only pathway which projects out of hemisphere)
The internal capsule is divided into the anterior limb (between ____________ and ________________) and posterior limb (between _________ and _____________):
• Various pathways pass through the internal capsule (some sensory up to the cortex; some from cortex down to other CNS structures)
head of caudate nucleus and lentiform nucleus;
thalamus and lentiform nucleus
What fibres are at the anterior limb of the internal capsule?
Thalamocortical (sensory; main pathway taking information up to cortex from the thalamus), corticopontine (from cortex towards pontine nuclei)
What fibres are at the posterior limb of the internal capsule?
Thalamocortical, corticopontine
Fibres controlling movement (corticospinal corticobulbar to motor nuclei in brainstem)
Cerebrovascular accident: strokes which cause the loss of blood supp ly to the internal capsule may have different effects on movement
Posterior limb : ___________________
Anterior limb : ____________________
loss of voluntary movement on the contralateral side;
no effect on voluntary movement (no tracts controlling movement)
The ________________ receives information from the retina and the information is projected onto the________________ (further analysis):
• Individual features of the image are separated and dealt with separately (e.g. one part involved with movement in the image, another involved with colour)
• Damage: may affect one particular feature of vision without making the subject completely blind (if limited)
primary visual cortex;
occipital association cortex
The parietal lobe possesses the _________________- which receives information about touch and proprioception and passes it to the _________________:
• Involved in setting up an understanding of spatial relationships (receives information from the primary somatosensory cortex and primary visual cortex)
• Damage: patient is likely to be _______________________
primary somatosensory cortex;
posterior parietal cortex;
disoriented (e.g. cannot follow a map accurately, no longer understand relationship of different parts of body to immediate surroundings → producing
specific syndromes like hemineglect)
The temporal association cortex is involved in language, vision, memory, emotion:
- Language: Area surrounding the _________________ cortex is concerned with language (understanding and comprehension ) –> Damage: _____________
- Vision: Visual functions in the temporal and occipital lobes (particularly object recognition) –> Damage: ____________
- Memory: Areas (particularly on the _______________) involved in memory consolidation –> damage: Amnesia (memory loss)
- Emotion: Structures associated with the _______________ –> damage: Emotional instability
primary auditory;
Receptive aphasia (difficulty understanding);
Agnosia (difficulty recognising);
medial surface of temporal lobe;
medial temporal cortex which are part of the limbic system (emotion and mood)
The frontal lobe forms a large part of the cortex, with the posterior areas involved in motor control (_____, ________, _______):
• _____________ (anterior part of frontal lobe) is involved in higher functions involving cognition (e.g. judgement, decisions, foresight, planning) and social interaction → major contributor to defining the individual personality
• Damage: patient becomes confused, unable to make value judgements, indecisiveness, unable to plan/organise life and personality disorders (makes social interactions more difficult)
primary motor cortex, premotor cortex, supplementary motor area
Prefrontal cortex
DECISION MAKING & SELF-CONTROL
A study was conducted to investigate decision making and self-control, involving a number of subjects who were actively dieting asked to choose between foods which differed in taste and healthiness while they were scanned with fMRI:
• Particular parts of the ventromedial prefrontal cortex were reliably active each time they made a valued judgement
• ______________ was always active regardless of the choice, but only the group with strong self-control had active ______________
Ventromedial prefrontal cortex;
dorsolateral prefrontal cortex
