MDG5204 Chap.8 Neurotransmission and Basal Ganglia Motor Circuits
Neurotransmission and Basal Ganglia Motor Circuits
Neuropharmacology as its own layer
The second theme applies the pharmacology of the first to the nervous system. Neuropharmacology asks how chemical substances change the way the nervous system works, how it is built and its chemistry.
The lecture warns that the more complex the level of organisation, from molecule to cell to organ to behaviour, the harder it becomes to predict a drug's effect, which is why the chapter starts with the building blocks.
How neurons signal
Signalling within a neuron is electrical and between neurons chemical.
The resting membrane potential of about −70 mV comes from selective permeability to potassium over chloride and sodium and from the sodium-potassium pump. A depolarising stimulus that reaches about −50 mV opens voltage-gated sodium channels; the membrane swings towards +50 mV; sodium channels inactivate and potassium channels open, repolarising and briefly hyperpolarising the cell.
Sodium channel inactivation sets the absolute refractory period, and myelin allows saltatory conduction between nodes of Ranvier.
The synapse and its drug targets
At the terminal, voltage-gated calcium channels open and calcium entry lets vesicles dock and release transmitter.
Postsynaptic ion channels or G protein-coupled receptors carry the signal on; enzymes and reuptake transporters end it; presynaptic autoreceptors limit further release; and receptor internalisation can desensitise the postsynaptic cell, one mechanism for tolerance. Acetylcholine illustrates every step, from synthesis by choline acetyltransferase to breakdown by acetylcholinesterase, and each step is a potential drug target.
Glutamate and GABA are the main excitatory and inhibitory transmitters, and dopamine, from the substantia nigra, serves movement and reward.
The basal ganglia and movement
The basal ganglia, including the striatum, globus pallidus, subthalamic nucleus and substantia nigra, select actions by releasing inhibition on selected motor systems.
In the direct pathway, cortical excitation of the striatum inhibits the internal globus pallidus, releasing the thalamus and favouring movement; in the indirect pathway, a longer chain through the external globus pallidus and subthalamic nucleus ends in more inhibition of the thalamus and less movement.
Dopamine excites the direct pathway through D1 receptors and inhibits the indirect one through D2 receptors, which is the key to the next chapter.
What this chapter covers
- 01
Neuropharmacology defined and why complexity limits prediction
- 02
Resting membrane potential and the ion-channel sequence of the action potential
- 03
Calcium-triggered transmitter release, termination and autoreceptors
- 04
Glutamate, GABA, acetylcholine and dopamine
- 05
Direct and indirect basal ganglia pathways
- 06
Dopamine acting through D1 and D2 receptors in the striatum
Worked example · free
Following the indirect pathway to its effect
- 2Trace cortex to striatum to external globus pallidus.
- 2Trace subthalamic nucleus to internal globus pallidus to thalamus.
- 2State the net effect on the cortex and movement.
Key terms
- Resting Membrane Potential
- The voltage across a resting neuron's membrane, about minus 70 mV.
- Action Potential
- A brief all-or-none reversal of membrane potential carried by sodium entry and potassium exit.
- Refractory Period
- The interval after an action potential when a neuron cannot fire, or fires only to a stronger stimulus.
- Autoreceptor
- A presynaptic receptor that responds to the neuron's own transmitter and limits further release.
- Basal Ganglia
- Deep brain nuclei that select actions by releasing inhibition on chosen motor programmes.
- Direct Pathway
- The basal ganglia route through the internal globus pallidus whose activation favours movement.
Neurotransmission and Basal Ganglia Motor Circuits FAQ
Why does the inside of a resting neuron sit at a negative voltage?
The resting membrane is far more permeable to potassium than to sodium, so potassium leaking out leaves the inside negative, and the sodium-potassium pump maintains the gradients. The result is a resting potential of about minus 70 mV, from which depolarisation starts.
How is a chemical signal at the synapse switched off?
By removing the transmitter from the cleft, either by enzymatic breakdown, as acetylcholinesterase does for acetylcholine, or by reuptake transporters. Presynaptic autoreceptors also dampen further release, and prolonged stimulation can internalise postsynaptic receptors.
Why does dopamine favour movement through two opposite pathways?
It acts on different receptors in each. Through excitatory D1 receptors it strengthens the direct pathway, which promotes movement; through inhibitory D2 receptors it weakens the indirect pathway, which would otherwise suppress movement. Both effects push in the same direction.
Exam move
Draw the direct and indirect pathways from memory with signs on every arrow, then add dopamine at D1 and D2. Repeat until you can predict the effect of losing dopamine without looking, because the next chapter depends on it.
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