The neurone Flashcards
How can it be established that Cl- is distributed passively across neuronal membranes?
Their Nernst potential (Ecl) is approximately equal to the resting membrane potential (Vm).
What is the Donnan product rule?
[K+]out[Cl-]out = [K+]in[Cl-]in
Why do developing neurones have large numbers NKCC1 channels?
- Allows for active transport of Cl- ions into the neurones, which increases [Cl-].
- This allows for spontaneous efflux of Cl- out of neurones at rest as a result of opened Cl- channels, causing spontaneous depolarisation.
- Spontaneous depolarisation of developing neurones generate APs that are important for mediating development.
What are the different components of the NT exocytosis mechanism?
- Ca2+ sensor: Synaptotagmin
- V-SNARE: Synaptobrevin
- T-SNARE: Syntaxin & SNAP-25
What is the relationship between post-synaptic depolarisation (V) and pre-synaptic [Ca2+]?
V is proportional to [Ca2+]4
What are the criteria needed for a chemical to be regared a NT?
- It must be present in pre-synpatic terminal.
- It must be released into synaptic cleft from pre-synaptic terminal on stimulation.
- Added chemical must have same post-synaptic effect as released NT.
- Action of added transmitter must be inhibited by same inhibitors as natural transmitter.
What are the classes of NTs present in the CNS?
- Amino acids
- Bioactive amines
- Purines
- Neuropeptides
- Gaseous NTs
What are the amino acid transmitters?
- Glutamate - Excitatory
- GABA (γ-amino butyric acid) - Inhibitory
- Glycine - Inhibitory
What are the bioactive amines?
- Catecholamines
- Dopamine
- Serotonin
- Histamine
- Acetylcholine
What are the purines?
- ATP
- Adenosine
What are the gaseous transmitters?
- NO
- CO
- H2S
What is the significance of gaseous transmitters?
Unlike the other classes of NTs, they are not pre-made and stored in the pre-synaptic membrane as they are highly diffusible. Instead, they are synthesised on demand.
What are the ionotropic glutamate receptors?
- NMDA
- Non-NMDA:
1. AMPA
2. Kainate
What are the approximate timescales of action for different NT receptors?
- Ionotropic: msec
- Metabotrophic:
1. GPCRs: sec - min
2. RTKs (hormones & enzymes): Min - days
What are the 2 categories of receptor types?
- Long receptor: Sends axons straight to the CNS from area of reception.
- Short receptors: Synapses with second order cell that sends axons into the CNS.
What is the sequence of events in long receptor signal transduction?
- Stimulus causes ion channels to open.
- Receptor potential proportional to stimulus magnitude created.
- RP with sufficient magnitude triggers APs.
- Frequency of APs proportional to magnitude of RP.
What are examples of long receptors?
- Somatosensory receptors
- Olfactory receptors
What is the sequence of events in short receptor transduction?
- Stimulus opens ion channels in receptor cell.
- RP proportional to magnitude of stimulus generated.
- RP conducted passively along receptor cell until it reaches pre-synaptic membrane, where it causes voltage-gated Ca2+ channels to open.
- Influx of Ca2+ results in induction of exocytosis of NT vesicles and release of NTs into synaptic cleft.
- NT binds to post-synaptic receptors and triggers EPSP.
What are examples of short receptors?
- Taste receptors
- Auditoru receptors
- Photoreceptors
What are the forms of receptor signal transduction?
- Direct transduction
- Indirect transduction
What are the benefits of indirect tranduction over direct transduction?
- Diversity: One stimulus can cause multiple responses.
- Amplification: Small magnitude stimulus can cause large response.
- Adaptation: More flexibility and more mechanisms available for adaptation.
What are the criteria that need to be fulfilled for 2 EPSPs to sum?
- They need to be sufficiently close to each other in time due to time constant.
- They need to be sufficiently close to each other in space due to space constant.
- They cannot be too close to each other else occlusion may occur.
What are the different types of synapses with regards to their position along the post-synaptic neurone?
- Axo-somatic synapse: Synapse with body (soma) of post-synaptic neurone.
- Axo-dendritic synapse: Synapse with dendrites of post-synaptic neurone.
- Axo-axonic synapse: Synapse with axons of post-synaptic neurone.
What are the types of inhibition?
- Voltage inhibition
- Current inhibiton (shunting inhibition)
- Pre-synaptic modulation
What are the differences in distrubution of excitatory/inhibitory synapses along a post-synaptic neurone?
- Excitatory synapses are mostly axo-dendritic.
- Inhibitory synapses are mostly axo-somatic.
- Having inhibitory synapses closer to soma than excitatory ones allow for more effective shunting inhibition, which is more powerful.
What are the mechanisms by which pre-synaptic inhibition can be achieved?
- Axo-axonic synapses cause pre-synaptic depolarisation, leading to inactivation of Navs and decreased magnitude of APs.
- Inhibition due to IPSP decreases magnitude of APs.
- Secondary messengers via metabotrophic receptors (e.g. α2-adrenoreceptors) decrease influx of Ca2+.
What are the criteria that need to be met in order for pre-synaptic inhibition to be effecive?
- Timing is crucial and the inhibitory signal needs to arrive at virtually the same time as AP.
- Arriving too early means inhibitory effects become attenuated when AP arrives.
- Arriving too late obviously results in no effect.
What is the advantage of pre-synaptic inhibition over post-synaptic inhibition?
More selective inhibition of certain selective excitatory inputs instead of general inhibition of all excitatory inputs.
What is the function of the A current (IA)?
- IA is active when the neurone is polarised and acts as an outward K+ current clamping the membrane at the RP. When a stimulus causes NaVs to open and inward depolarising Na+ currents to occur, they are reduced by IA, reducing rate of depolarisation. As neurone becomes depolarised, IA inactivates, allowing further depolarisation to threshold and thus AP to be produced.
- IA effectively spaces out APs along spike trains.
- Stimulus of greater magnitude causes faster depolarisation and faster inactivation of IA.
What is the process of AP bursting in neurones?
- Neurone is depolarised by initial stimulus and RP.
- Depolarisation causes T-type Ca2+ channels to activate and an inward Ca2+ current that depolarises neurone much more quickly.
- Once threshold is reached, AP is generated.
- Several APs fire in rapid succession, significantly increasing intracellular [Ca2+].
- Ca2+-activated K+ channels are activated, producing outward K+ current that terminates bursting.
- Ca2+ is extruded from neurone by NCX and PMCAs, inactivating K+ current and allowing burst cycle to repeat.
What are the functions of Ca2+-activated K+ channels in bursting neurones?
- Reduces firing frequency of bursts, allowing time for T-type Ca2+ channels to reactivate following AP in burst.
- Becomes greater after each AP in burst due to higher [Ca2+]i, steadily hyperpolarising neurone and eventually terminating burst.
- Allows for spike frequency adaptation and the steady decrease in firing frequency over time.
What is the physiological significance of AP bursting in neurones?
Allows for neurones that need to be tonically activsted to ‘break’ during prolonged stimulation, preventing complete inactivation of APs.
What are the types of synaptic branching?
- Convergence
- Divergence
What is the “subliminal fringe” of a stimulus unit?
Group of motor neurones that receive EPSPs from group of 1A affterents, but is insufficient to depolarise neurone to threshold and generate AP.
What are the types of summation that can occur between stimulus units?
- Linear summation: When stimulus units are non-overlapping and so stimulation of 2 units produce response which is sum of 2 individual unit responses.
- Supralinear summation: When the stimulus units are overlapping and so stimulation of 2 units result in stimulation of some fibres in suliminal fringe, resulting in the overall response being greater than sum of unit responses.
- Occlusion: If there is too much overlap, then 1A fibres from 2 units may in turn stimulate the same motor neurones and so have ‘wasted’ effect, resulting in overall response being less than the sum of unit responses.
What are the types of neuronal inhibition?
- Feedforward inhibition
- Feedback inhibition
What is the function of feedforward inhibition?
To allow for inhibition of antagonistic muscle groups during muscle reflexes.
What are the functions of feedback inhibition?
- Prevents over-firing of motor neurone and fatigue.
- Stalilises neuronal firing rate so that firing rate is proportional to magnitude of stimulating current.
- To allow for spike-frequency adaptation in motor neurones.
What is the mechanism of post-tetanic potentiation?
After tetanus, Ca2+ stored intracellularly increases as a result of significant increase in [Ca2+]i during tetanus. This results in greater facilitation of vesicle priming, reulting in more NT being available for release upon post-tetanic stimulation.
What does Hebb’s law state?
An input is strengthened if it has a role in stimulating a firing cell, even if it alone cannot stimulate the same cell.
What is the mechanism of long-term potentiation?
- On post-synaptic membrane, NMDA (Glu) receptors (selective to Ca2+ ions) are present, along with AMPA recepors (non-selective cation channel).
- When the synapse is stimulated, Glu is released from the pre-synaptic terminal and binds to both NMDA and AMPA receptors.
- When Glu binds to NMDA, the channel opens, but is blocked by Mg2+ ions.
- However, when AMPA opens in conjunction with NMDA, influx of cations (mainly Na+) causes depolarisation, which makes NMDA Ca2+ permeable.
- Influx of Ca2+ causes a number of changes including:
- Increased AMPA receptor density
- Increased NO and arachidonic acid synthesis (both retrograde messenger that modulate NT release) - These changes increase the sensitivity of the synapse.
- They only occur if both NT present and depolarisation of post-synaptic neurone occurs.
What is the significance of multiple NTs in pre-synaptic membrane?
- In some pre-synaptic terminals, there may be multiple NTs and/or neuromodulators (e.g. neuropeptides).
- Neuromodulators may be held in bigger vesicles and so need sustained pre-synaptic APs to ne released, while bursts of activity favours NT release alone.
- Neuromodulators don’t cause post-synaptic potential themselves. Instead, they change the post-synaptic effects of the NT.
What are the functions of inhibition in the CNS in general?
- To inhibit antagonistic groups of effectors in a reflex.
- To control an excitatory signal and prevent explosive chain reaction of excitation throughout CNS, restricting excitation to only the desired pathway.
What are the benefits of pre-synaptic inhibition over post-synaptic inhibition?
There is greater percision, so that the actual sources of the excitatory inputs can be targeted individually, not just the post-synaptic neurone receiving inputs from a number of different sources.
What are examples of neuropeptides?
- Neuropeptide Y (NPY)
- Substanc P
- Vasoactive intestinal peptide (VIP)
- Cholecystokinin (CCK)
- Calcitonin gene-related peptide (CGRP)
What are the functions and disadvantages of dendritic spines?
- Function: Chemical/electrical isolation of excitatory inputs so that they are not affected by changes in rest of neurone.
- Disadvantage: High resistance attenuates excitatory input.
