0407 - Neuro excitation, inhibition and modulation - CS Flashcards
Describe what it means for a synapse to be excitatory
- Increases excitability of POST synaptic membrane.
- Results in a EPSP (Excitory Post Synapse Potential) and brings the membrane voltage closer to the action potential threshold, increasing the probability of an action potential
- Most commonly glutamatergic (use glutamate or aspartate as neurotransmitters)
- Most commonly opens a non-selective Na+/K+ ion channels (a type of fast ionotropic or ligand-gated receptor)
- Decreases Cl- and K+ conduction (this raises the membrane voltage)
- Involves the activation of receptor enzymes and metabolic pathways that increase the expression of excitatory, or decrease inhibitory membrane receptors
- NMJ- Neuromuscular junction is one type of synapse and it is always excitatory
- Neuron-neuron synapses may be excitatory, inhibitory or modulatory
Which neurotransmitters are commonly used in excitatory synapses?
Glutamate - excitatory (main one)
Aspartate - excitatory
Acetylcholine - can be excitatory OR inhibitory
Describe what it means for a synapse to be inhibitory
- Inhibitory - decreases excitability of POST synaptic membrane
- Result in an IPSP (Inhibitory Post Synapse Potential) and bring the membrane voltage further away from the action potential threshold, decreasing the probability of an action potential
- They are typically GABAergic or glycinergic (use GABA or glycine as neurotransmitters)
- Most commonly open selective Cl- channels (a type of fast ianotropic receptor)
- Increase K+ conductance (this reduces the membrane voltage)
- Involves the activation of receptor enzymes and metabolic pathways that increase the expression of inhibitory, or decrease excitatory membrane receptors
Which neurotransmitters are commonly used in inhibitory synapses?
GABA - inhibitory (main one)
glycine - inhibitory
Acetylcholine - usually excitatory EXCEPT for inhibitory effect in slowing the heart
Describe what it means for a synapse to be modulatory
- Indirectly changes the excitability of the pre OR post-synaptic membrane.
- Regulates or modifies the effects of other inhibitory or excitatory synapses - may ‘dampen’ or ‘brighten’ the response to other neurotransmitters by making the synapse more or less sensitive to other neurotransmitters
- There are many forms of synaptic modulation. Mechanisms are complex and diverse and response depends on the receptor being activated.
- Generally mediated by slower metabotropic receptors that activate a signalling cascade
Which types of neurotransmitters are commonly used in modulatory synapses?
Lots:
- Bionogenic amines
- Purines
- Peptides
- Lipid molecules
- Gasses
Extra question: explain the concept of the ‘reversal potential’ in relation to EPSPs and IPSPs
EPSP
- In a typical excitatory synapse, a neurotransmitter binds to receptors on the post-synaptic membrane and non-selective Na+/K+ channels are opened
- Initially Na+ rushes through the channels into the cell down the NA+ electrochemical gradient. Eventually the synapse reaches a point where the Na+ and K+ currents through the channel are equal and opposite and there is no net current and no EPSP. This is known as the reverse potential. Ie. reverse potential is usually close to 0mV for excitatory synapses
IPSP
- In a typical inhibitory synapse, a neurotransmitter binds to receptors on the post-synaptic membrane. This opens a selective channel - permeable to only one ionic species (Cl- or K+).
- Therefore, IPSPs have a reversal potential equal to the Nerst potential of the ion carrying the underlying current. Typically this is negative to resting potential, so when IPSP channels open there is an outward flow of current through them that results in hyperpolarization of the membrane
What is the difference between ionotropic and metabotropic receptors and give an example of neurotransmitters that typically acts on each
Ionotropic receptors
- Protein complexes that span the membrane and have an extracellular binding site for the neurotransmitter to attach to.
- Receptor contains an ion channel as an integral part of the receptor itself (a ligand-gated receptor)
- the neurotransmitter binds to the receptor. The receptor becomes a channel that opens to enable ions to pass through
- enables fast synaptic transmission but with short duration
Metabotropic receptors
- does not contain an ion channel
- is coupled to a G protein. The neurotransmitter binds to the receptor, which initiates second messenger cascades that can ultimately affect ion channels.
- each G protein can open multiple channels
- allow signal amplification but slower than ionotropic (with long duration)
Examples of neurotransmitters that act on ionotropic receptors:
- Glutamate
- GABA
- Acetylcholine
- Glycine
Examples of neurotransmitters that act on metabotropic receptors:
- Glutamate
- GABA
- Acetylcholine
- Dopamine
- Histamine
Discuss Glutamate (Glu) in terms of its actions, synthesis and degradation
Glutamate is a type of amino acid
Actions:The major excitatory neurotransmitter throughout the central nervous system (CNS)
Synthesis: very simple synthesis; No specific degrading enzymes
Degradation: Transporters are used to transport Glu out of the synapse either into astrocytes (to be converted into inert glutamine via the enzyme glutamine synthase) or into the nerve terminal (for reuse).
*Glu is potently neurotoxic so its deactivation is highly controlled - via diffusion and re-uptake.
Receptors that glutamate acts on may be ionotropic OR metabotropic. List three ionotropic receptors that glutamate acts on
- AMPA - CNS excitation. Fast
- NMDA - mediates synaptic plasticity. Slow
- Kainate (KA) - regulates the release of GABA. Fast
Consider Acetylcholine (ACh). Describe its actions, synthesis and degradation
Actions: - Generally excitatory except for its slowing effect on the heart
- Peripheral nervous system: in motor neuron terminals
- Autonomic nervous system: in preganglionic neurons of the ANS, in postganglionic neurons of the parasympathetic nervous system, few postganglionic sympathetic neurons
- Central nervous system: in motor cortex, basal ganglia, basal forebrain projections to hippocampus and amygdala, brainstem nuclei, spinal cord, implicated in memory function and associated with Alzeimer’s
Synthesis: Synthesised from acetyl coenzyme A and choline by the enzyme choline acetyltransferase which is located in the cytoplasm of cholinergic presynaptic terminals
Degradation: Its action is terminated by the enzyme acetylcholinesterase and hydrolyzed into acetate and choline. The choline is taken up by an Na+ simporter in the presynaptic membrane for resynthesis
What important receptors does acetylcholine act on? Are they ionotropic or metabotropic? Where are they found?
- Ionotropic ACh receptor - nicotinic
- found in the neuromuscular junction
- within the central nervous system
- non-selective Na+/K+ channel - Metabotropic ACh receptor - muscarinic
- 5 known types (M1 - M5)
- vagal efferents innervating the heart
Consider GABA. Describe its actions, synthesis and degradation.
Actions and locations: The most abundant inhibitory neurotransmitter
Mostly found in interneurons
Also GABAergic projection neurons that suppress their output targets:
- spiny neurons of the striatum
- purkinje cells of the cerebellar cortex
Synthesis: Produced from glutamate via glutamic acid decarboxylase (GAD) (GAD only present in inhibitory neurons)
Very simple synthesis (depends on glutamate synthesis); no specific degrading enzymes
Deactivation: Via diffusion, uptake into glia and reuptake as glutamine
There are specific GABA transporters (GAT1 - GAT4)
Are the receptors that GABA acts on ionotropic, metabotropic or both?
Both
List 7 classes of neurotransmitter and give an example of each
- Gasses - NO, CO
- Amino acids - glutamate, GABA, glycine, aspartate
- Monoamines - achetylcholine, serotinin, histamine
- Catacholamines - dopamine, noradrenaline, adrenaline
- Purines - adenosine, ATP
- Lipid metabolites - endocannabinoids
- Peptides - lots of them. eg hormones (eg oxytocin), opioids
