Topic 5: Nervous System Flashcards
Label the features below as NMJ or CNS:
- One presynaptic neuron
- Integration can be complex, e.g. coincidence, summation etc
- EPP is excitatory
- AP frequency and the number of recruited fibres determine strength of muscle contraction
- Synaptic transmission is unreliable: a single presynaptic ap alone rarely triggers postsynaptic ap
- Use many different neurotransmitters, not just ACh
- NMJ - CNS has many presynaptic neurons
- CNS - NMJ excludes integration
- NMJ - CNS can be inhibitory or excitatory
- NMJ - Frequency, timing and neuronal identity important for CNS info
- CNS - NMJ signal reliably triggers ap
- CNS - NMJ just uses ACh
What are the 2 coding schemes used by the CNS neurons to represent information and how do they work?
- Stimulus Intensity: Rate and Population codes
- Stimulus Modality: Labelled line code, each sensory neuron encodes 1 stimulus modality
There are 2 mechanisms by which synaptic inputs can be integrated, what are they? (hint = ‘X’ Summation)
Temporal summation: Detects high frequency firing y upstream neurons
Spatial summation: Detects coincident firing of upstream neurons
Match the types of central synapses to their attachment points:
a) Axodendritic
b) Axosomatic
c) Axoaxonic
1- Axon attaches directly to the cell body (soma)
2- Axon attaches to the axon of another neuron
3- Axon attaches to the dendrite of target cell
a) 3
b) 1
c) 2
How can excitatory and inhibitory synapses be identified in relation to their membrane differentiations?
Gray’s Type I Excitatory: Assymetrical membrane differentiations
Gray’s Type II Inhibitory: Symmetrical membrane differentiations
Stimulus intensity can be encoded by a)_______ and b)_________ codes. (b) code refers to the number of axons that are activated / conveying the signal. (a) codes refer to the frequency of action potentials conveying the signal. Central neurons may also use c)S_____T____C_____ for representing information
a) Rate
b) Population
c) Spike timing codes
Label the below statements as features of GluA/K (AMPA) receptors or GluN (NMDA) receptors or both:
a) Play a crucial role in synaptic plasticity, learning and memory
b) Mediate fast excitatory neurotransmission
c) Subtype of ionotropic glutamate receptor
d) Activation allows influx of Na and K leading to excitatory postsynaptic potentials (EPSPs)
e) Require 2 conditions for activation, binding of glutamate + relief of Mg blockage from receptor channel
f) Involved in long term potentiation (LTP)
g) Mainly found in the forebrain
a) Both
b) GluA/K (AMPA)
c) GluN (NMDA)
d) GluA/K (AMPA)
e) GluN (NMDA)
f) GluN (NMDA)
g) GluA/K (AMPA)
Describe key molecular properties of glutamate receptors. How many transmembrane domains do they have + what else?
-3 transmembrane domains + a re-entrant loop
Give 3 reasons why it is thought that glutamate receptors are crucial in memory development and retention
- High densities of glutamate activated channels are found in regions of the brain associated with memory function / learning
- Drugs that block glutamate action (block NMDA receptors) inhibit learning and memory
- Drugs that potentiate the actions of glutamate enhance learning + memory
Synthesis and release of Glutamate:
Glutamate is synthesised by the a)_________ but is altered and stored as b)_________ in the presynaptic neuron. When it is needed, (b) is converted back to glutamate via the enzyme c)___________ (PAG) in the presynaptic neuron.
Glutamate is then released via exocytosis, acts on the postsynaptic receptor and undergoes reuptake via d)______________ that transport it to the glial cell
-Glutamine
- Excitatory amino acid transporters (EAATs)
-Phosphate activated glutaminase
-Glial cell
a) Glial Cell
b) Glutamine
c) Phosphate activated glutamiase
Glutamatergic synaptic currents have a fast and slow component:
a) what mediates the fast component
b) what mediates the slow component
-NMDA receptors
-AMPA receptors
a) AMPA
b) NMDA
What is the difference between Ionotropic Glutamate Receptors (iGluRs) and Metabotropic Glutamate Receptors (mGluRs)?
iGluRs:
- membrane ion channels gated by glutamate
mGluRs:
- 7 transmembrane domain proteins that couple to G proteins
- 3 distinct categories (Group I, II & III)
Describe pathways for synthesis, release and breakdown of GABA
Explain how GABA receptors cause inhibition
Understand the molecular subtypes of GABA receptor and their functional diversity
Match the receptor to the receptor type:
a) Metabotropic G-coupled receptor
b) Ionotropic
- GABA(a)
- GABA(b)
a) GABA b
b) GABA a
Discuss the importance of GABA receptors as targets for pharmacological modulation in relation to benzodiazepines
- Benzos potentiate the action of GABA at GABA(a) receptors by increasing probability of gate opening when GABA binds
- Benzos bind Gamma-2 subunit making response larger and slower
- Can be used to treat epilepsy
Match the receptors and the associated function to the mechanism of synaptic transmission:
a) Nicotinic - Na+ / K+
b) AMPA / kinate - Na+ / K+
c) mGluRs - G-proteins
d) Muscarine - G-proteins
e) NMDA - Na+ / K+ / Ca2+
f) GABA(a) - Cl-
g) GABA(b) - G-proteins
h) Glycine - Cl-
- Acetylcholine
- Glutamate
- Glycine
- GABA
a) Cholinergic
b) Glutamatergic
c) Glutamatergic
d) Cholinergic
e) Glutamatergic
f) GABA
g) GABA
h) Glycine
GABA and Glycine are both a)_________ neurotransmitters that mediate b)____ ______ _______
through activation of c)_________ receptors.
- Fast synaptic inhibition
- Inhibitory
- Ionotropic
a) Inhibitory
b) Fast Synaptic transmission
c) Ionotropic
a) How is GABA synthesised?
b) How is Glycine synthesised?
a) Glutamic acid decarboxylase acts on glutamate to form GABA
b) Serine hydroxyl-methyltransferase acts on serine to make glycine
GABA is the major inhibitory neurotransmitter in the mammalian CNS and the GABA(A) receptor is the site of action of many drugs such as benzos, ethanol & neurosteroids.
What can a) too much and b) too little GABA cause
a) Loss of consciousness
b) Seizures
There are 2 types of GABA receptors, GABA(A), an ionotropic receptor and GABA(B) a metabotropic G-coupled receptor.
What is the function of a) GABA (a) and b) GABA (b)?
a) When GABA binds to a GABA (a) receptor, an associated chloride channel opens allowing influx of Cl- into the cell, essentially hyperpolarising it making it less likely to generate an action potential. FAST IPSP
b) When GABA binds GABA (b), K+ channels open and Ca2+ channels close, allowing K+ to leave the cell also hyperpolarising the cell. SLOW IPSP
The action of GABA is terminated by GABA transporters (GAT). What do they do?
Transport GABA from the synaptic cleft into glial cells or back the the presynaptic nerve where it is degraded by enzymes
True or false, both GABA(a) and glycine receptors are ionotropic and conduct Cl- ions
True
What is the word used to describe the multimeric macromolecular GABA(a) receptor (and glycine receptor)? (hint = to do with number of subunits)
Bonus q: What is the structure of glutamate receptors?
Pentameric (4 transmembrane domains)
Bonus = Tetrameric
The compound AP-V been useful in study of memory because it specifically blocks GluAs.
True or False
False
Ionotropic glutamate receptors cause depolarization by allowing K+efflux.
True
False
False
Which of the following is FALSE?
a) Glutamate is an excitatory neurotransmitter
b) All ionotropic glutamate receptors conduct Na+ and K+ ions
c) Glutamate is an excitatory neurotransmitter
d) Activation of more than one glutamatergic synapses is usually required to make a postsynaptic neuron fire an action potential
e) The driving force for Cl- ions determines the reversal potential of glutamatergic postsynaptic responses
e)
Which of the following does not apply to the NMDA sub-type of glutamate receptor ?
a) The amplitude of the receptor current is determined by the driving force for Na+ ions
b) The amplitude of the receptor current depends on membrane potential
c) The amplitude of the receptor current can be attenuated by intracellular Mg2+ ions
d) The amplitude of the receptor current is reduced by D-APV
c)
Which of the following ionotropic receptors is assembled as a tetramer (from four subunits)?
a) NMDA sub-type of glutamate receptor
b) GABA-A receptor
c) AMPA- sub-type of glutamate receptor
d) Nicotinic acetylcholine receptor
a & c
Which of the following would a brief (~1s) train of high frequency (~100 Hz) stimuli to a glutamatergic synapse in the hippocampus NOT be expected to do?
a) Activate NMDA receptors
b) Activate the enzyme glutamic acid decarboxylase
c) Increase the strength of the activated synapses
d) Cause an influx of Ca2+ at the synapses
b)
