Lecture 4 Neurophysiology and Neurotransmission Flashcards
Where on the neuron do excitation and inhibition typically occur?
Excitation typically occurs on dendrites (axo-dendritic synapses), and inhibition typically occurs on the cell body (axo-somatic synapses)
Describe the general mechanism behind excitatory post-synaptic potentials and inhibitory post-synaptic potential.
EPSP: Glutamate receptor activation opens Na+ channel; Na+ influx depolarization to ~ 0 mV; K+ efflux small contribution. IPSP: GABA(A) receptor activation opens Cl- channel Cl- influx hyperpolarization Glycine receptors (spinal cord), small amount
Describe the structure of ligand-gated ion channels
5 subunits (alpha, beta, gamma, delta, epilon) for the channel pore. *nicotinic acetylcholine receptor (nAchR) does not contain epsilon subunit. Each subunit is made up of 4 alpha-helices (m1, m2, m3, ma4). The alpha subunit binds ligand (acetylcholine). The pore is not selective.
Describe how synaptic transmission occurs, including the key proteins involved.
The action potential enters the synaptic terminal and opens n-type voltage-gated Ca2+ channels; Ca2+ influx causes synaptic vesicles to fuse with presynaptic membrane. The neurotransmitter is released, and binds postsynaptic receptors.
Key proteins:
Vesicle-associated membrane proteins (VAMPs): synaptobrevin: “docking” protein, synaptotagmin-1: binds Ca2+.
Synaptic membrane proteins: syntaxin/SNAP-25 complex, VG Ca2+ channel (n-type).
Ca2+ binds synaptotagmin-1 which then binds synaptobrevin. Steps trigger Fusion Pore Complex formation and neurotransmitter release.
What is the difference between spatial and temporal summation?
Spatial summation is when EPSPs from several presynaptic inputs occur within a critical distance, whereas temporal summation is when EPSPs from a single presynaptic input occur in a short interval.
In the spinal cord; what is the dorsal horn responsible for? the ventral horn?
Dorsal horn- sensory projection to brain
Ventral horn- motor neurons that contract skeletal muscle
Receptors can be classified into two different groups; ligand-gated ion channels and G-protein coupled receptors (GPCRs), what defines these two groups?
Ligand-gated ion channels: inontropic and fast receptors
GPCRs: metabotropic and slow receptors
What does botulinum toxin do to neurons?
Exopeptidase cleaves synaptobrevin, syntaxin and SNAP-25 causing loss of ACh release.
Alpha-Latrotoxin from a black widow causes what?
Alpha-Latrotoxin opens voltage gated Ca2+ causing excessive neurotransmitter release.
Define synaptic fatigue and benefits of it.
synaptic fatigue is when prolonged repetitive stimuli depletes neurotransmitter stores, requiring rest to be restored. This protects against glutamate neurotoxicity (excessive neuronal activity increases Ca2+ which is toxic)
What are the 6 receptor classifications?
- ACh receptors (nicotinic ACh receptors, fast, exc; muscarinic ACh receptors, GPCR, inh)
- NE/Epi always GPCR
- Serotonin (5 types): 5-HT1,2,4,5 are GCPRs; 5-HT3 is fast, inhibitory (K+ channel)
- Dopamine R-GPCR, mixed
- Glutamate R-fast, exc; GPCR mixed
- GABAa, glycine R-fast, inh; GABAb-GPCR mixed
Describe the structure of metabotropic receptors and provide another name for them.
G-protein coupled receptors are made up a of a single polypeptide made up of 7 membrane-spanning domains. There are metabotropic receptors for glutamate and GABAa.
Explain how acidosis, alkalosis, and hypoxia modulate neuronal excitability.
Acidosis decreases neuronal excitability; the decrease in pH from 7.4 to 7.0 can induce stupor and coma.
Alkalosis increases neuronal excitability; the increase in pH from 7.4 to 8.0 causes epileptic seizures.
Due to the brain’s high metabolism and oxygen dependence, interrupting blood flow 3-7 seconds leads to unconsciousness, and could lead to neuronal death in less than 5 minutes.
Which neuronal excitatbility modulator is a GABAA antagonist and a CNS mood elevator?
Benzodiazepine or Valium
Which neuronal excitability modulator is a dopamine reuptake inhibitor, where dopamine accumulation in the synpatic cleft activates the CNS reward pathway?
Cocaine
