NSCI1001 Introduction to the Brain Part III: Chemical Signaling

Ligand-gated channels

receptors for neurotransmitters

When a neuron responds to hyper/depolarization stimuli with a graded potential, where in the neuron does this take place?

dendrites

When a neuron responds to hyper/depolarization stimuli with an action potential, where in the neuron does this take place?

axon

synapse

transmit chemical signals from one cell to the next

where on the neuron is the presynaptic terminal? how much space is between neurons in the synaptic cleft? where on the neuron is the postsynaptic membrane?

axon terminal; \~50 nm; dendrite

What are the seven steps in synaptic transmission?

1. action potential arrives at axon terminal
2. Ca +2 channels open allowing Ca +2 to flow into the cell
3. synaptic vesicles fuse with the cell membrane
4. synaptic vesicles release neurotransmitters into the synapse
5. receptor activation
6. post-synaptic cell decides if it will fire an action potential


1. inactivation

step 1 of synaptic transmission

action potential: a depolarizing action potential arrives at the axon terminal

step 2 of synaptic transmission

Ca 2+ influx: voltage-gated Ca 2+ channels open allowing Ca +2 to flow into presynaptic cell

step 3 of synaptic transmission

movement of synaptic vesicles: Ca +2 causes the synaptic vesicles to move to the membrane and fuse with the membrane

step 4 of synaptic transmission

release: neurotransmitters are released into the synapse

step 5 of synaptic transmission

receptor activation: neurotransmitters in the synapse can freely move about; if they interact with a receptor (bind to it) they activate the receptor to stimulate electrical changes in the postsynaptic neuron post-synaptic electrical response; glutamate opens ligand-gated channels

step 6 of synaptic transmission

signal new action potential: cell body adds the graded inhibitory and excitatory potentials and decides whether to produce a new action potential

step 7 of synaptic transmission

neurotransmitter inactivation: neurotransmitters in synapse are either (a) altered into inactive substances or (b) recycled (reuptake) back into presynaptic vesicles

which glial cells have uptake mechanisms to inactivate glutamate?

astrocytes

how do neurotransmitters engage with the postsynaptic terminal?

they bind to receptors but do not enter

synaptic plasticity

synaptic transmission can be changed by experience

synaptic transmission

communication between neurons

What do long-term changes in synaptic transmission represent?

cellular basic of learning and memory

glutamate

most abundant excitatory neurotransmitter in CNS; learning and memory, neuronal death, seizure disorders (epilepsy)

GABA

most abundant inhibitory neurotransmitter in CNS; seizure disorders (epilepsy); mainly in brain

glycine

inhibitory neurotransmitter; mainly in spinal cord

acetylcholine

neuromuscular synapse (constructs muscles); learning and memory, Alzheimer’s disease

dopamine

reward, Parkinson’s disease, schizophrenia, drug addiction, happy signals

serotonin

sleep-wake cycle, depression

noradrenaline

sleep-wake cycle, alterness

neuropeptides

opioids (encephalin, endorphin, etc.), substance P, etc. (e.g. analgesics → painkillers)

pharmacological therapy

use of molecules to replace deficiencies in neurotransmitters (e.g. L-Dopa treats Parkinson’s)

how can we target the steps in chemical neurotransmission for drug therapies?

synthesis, chemical inactivation, reuptake, receptor activation

synthesis

L-Dopa used to treat Parkinson’s disease

chemical inactivation

MAOI’s (antidepressant drugs) block chemical inactivation, meaning there is more dopamine (and other neurotransmitters) in the synapse

reuptake

amphetamine blocks reuptake of dopamine into the presynaptic cell, which means there is more dopamine remaining in the synapse (used to treat ADD)

receptor activation

dopamine binds to two different receptors, D1 receptors which stimulate postsynaptic neurons (make them more positively charged) and D2 receptors which inhibit postsynaptic neurons (make them more negatively charged); anti-schizophrenic drugs like haldol (haloperidol) block these dopamine receptors and alleviate schizophrenic symptoms