Neuronal communication Flashcards
Ionotropic glutamate receptors e.g.
AMPAR/Kainate
NMDAR
Metabotropic glutamate receptors function by modulating …
NMDAR activity
Ionotropic GABA receptor channel
Directly increases Cl- influx
Metabotropic GABA receptor channel
Indirectly increases K+ efflux, decreases Ca2+ influx and inhibition of adenylyl cyclase
Which neurotransmitter has only ionotropic receptors?
Glycine
Inhibitory or excitatory: Glycine
Inhibitory
Inhibitory or excitatory: serotonin
Excitatory
Remark: Serotonin is 5-HT, has both ionotropic and metabotropic receptors
Inhibitory or excitatory: ATP
Excitatory
Inhibitory or excitatory: Ach
Excitatory
Migraine characteristics
Unilateral & pulsating, lasting 4-72 hours
Migraine etiology
Low levels of serotonin which causes vasodilation of extracranial vessels
Cortical spreading depression (CSD) symptoms
Aura - unusual visual, olfactory and other sensory experiences preceding migraine attacks
Which receptors contribute to the spreading of cortical spreading depression?
- Gap junctions
- NMDAR
Calcitonin gene-related peptide (CGPR)
Becomes elevated during migraine attacks. May be involved with vasodilation.
NMDA receptor antagonist
Meant to prevent CSD spread. DIRECT EFFECT, IONOTROPIC.
e.g. Magnesium, ketamine
Gap junction modulator
Meant to prevent CSD spread
e.g. tonabersat
5-HT receptor agonist
5-HT receptors are GPCRs that induce VASOCONSTRICTION. May help with CSD. INDIRECT: METABOTROPIC
e.g. Tryptans, ergotamine, kynurenine
CGRP receptor antibody
may help against CSD.
e.g. Erenumab (aimovig)
Can analgesics help with CSD?
yes.
Synaptogenesis at NMJ requires the formation of
basal lamina or laminin in the synaptic cleft
What happens with dysfunctional laminin?
Schwann cell processes invade the NMJ synaptic cleft. In humans, this causes congenital muscle dystrophy.
Nerve regeneration at NMJ
Basal lamina ghosts
Muscle regeneration at NMJ
Clusters of concetranted AchR
Gower’s sign
a patient has to use their hands and arms to “walk” up their body
What links the pre and postsynaptic membranes in central neuron junctions?
Adhesion molecules.
neurexin @ pre
neuroligin @ post synaptic
Mutation of neurexin-1
Schizophrenia
Mutation of neuroligin
Autism, mental retardation, repeated behaviors
How does glia help with synaptogenesis?
Secretion of thrombospondin and cholesterol
What is astrocytes’ function at synapses?
Lots of K channels
Buffer the excess accumulation of K
Abnormal accumulation of extracellular K results in epileptic neuronal activity
Electrical synapses are often…
Dendrodendritic
Axoaxonic synapse function
Presynaptic modulation
Renshaw cells
Renshaw cells are inhibitory interneurons found in the gray matter of the spinal cord, and are associated in two ways with an alpha motor neuron.
Cellular changes in short-term habituation
- Decrease of presynaptic Ca
- Decrease of transmitter release
Cellular changes in long-term habituation
- Decrease of sensory AP duration and absence of motor EPSP
- Decrease of synaptic connection numbers
Cellular changes in long-term sensitization
- increase of synaptic connection numbers
- Presynaptic facilitation: prolongation of the sensory neuron AP
How does presynaptic facilitation work?
5-HTergic local interneuron releases 5-HT into presynaptic neuron, which activates metabotropic pathways.
1. Ca2+ influx increases (MAIN EFFECT)
2. Increase of transmitter release
3. Postsynaptic facilitation of post EPSP
AXOAXONIC SYNAPSE
How does presynaptic inhibition work?
GABAergic local interneuron releases GABA into presynaptic neuron. AXOAXONIC SYNAPSE
1. GABAa ionotropic receptor increases Cl- influx, causing hyperpolarization
GABAb metabotropic r. increases K efflux and decreases Ca current
2. Decreased transmitter release
3. Inhibition of postsynaptic EPSP
Baclofen
GABA(B)R agonist
Effective in treating spasticity of spinal cord injury and MS.
Long-term Potentiation (early)
memory after high frequency stimulation
WHAT HAPPENS POSTSYNAPTIC DURING LTP?
1. NMDAR activation: wave of Ca enters
2. CaMKII activation
Ca and calmodulin cause retrograde (NO, nitric oxide, retrograde neurotransmitter), and tyrosine kinase, and PKC.
3. AMPAR insertion, AMPAR phosphorylation (increased conductance)
Next time the same stimulus is done, there can be more than twice the same postsynaptic EPSP.
Remark:
pre: CA3
post: CA1
Later LTP
Synaptogenesis
LTP VS sensitization
- Location: LTP occurs in the CNS (hippocampal).
- NT: LTP uses glutamate, Sensitization uses serotonin
- Method of increased postsynaptic EPSP: LTP increases postsynaptic conductance. Sensitization increases presynaptic transmitter release.
