This is pretty hard core stuff for the neurophysiology, neuropharmacology and neuroscience cognoscenti. You can skip it if you’re satisfied with our understanding of how the brain works, and our current treatments for neurological and psychiatric disease. You aren’t? Join the club and read on.
We thought we pretty much understood axons. They were wires conducting nerve impulses (action potentials) from the cell body to their far away ends, where the nerve impulses released neurotransmitters which then affected other neurons they were connected to by synapses.
We knew that there were two places on the axon where receptors for neurotransmitters were found, allowing other neurons to control what the axon did. The first was the place where axon leaves the cell body, called the axon initial segment (AIS). Some of them are controlled by the ends of chandelier cells — interneurons with elaborate specialized synapses called cartridges. The second was on the axon terminals at the synapse — the presynapse. Receptors for the transmitter to be released were found (autoreceptors) and for other neurotransmitters (such as the endocannabinoids (( our indigenous marihuana)) released by the presynaptic cell.
Enter a blockbuster paper from Science (volume 375 pp. 1378 – 1385 ’22) science.abn0532-2.pdf. It shows (in one particular case) that the axons themselves have receptors for a particular transmitter (acetyl choline) which partly can control their behavior. I sure people will start looking for this elsewhere. The case studied is of particular interest to the neurologist, because the axons are from dopamine releasing neurons in the striatum. Death of these neurons causes parkinsonism.
The work used all sort of high technology including G Protein Coupled Receptors (GPCRs) highly modified so that when dopamine hit them a fluorescent compound attached to them lit up, permitting the local concentration of dopamine to be measured in the living brain. Another such GPCR was used to measure local acetyl choline concentration.
The dopamine axons contain a nicotinic type receptor for acetyl choline. Stimulation of the interneurons releasing acetyl choline caused a much larger release of dopamine (in an area estimated to contain 3 to 15 million dopamine axon terminals. The area covered by dopamine release was 3 times larger than the area covered by acetyl choline release, implying that the acetyl choline was causing the axons to fire.
The cell body of the dopamine neuron had nothing to do with it, as the phenomenon was seen in brain slices of the striatum (which have no input from the dopamine cell bodies.
They could actually study all this in living animals, and unsurprisingly, there were effects on movement with increased striatal dopamine and acetyl choline being associated with movement of the animal to the opposite side.
So this is an entirely novel mechanism for the control of neural activity. How widespread such a mechanism is awaits further study, as is whether it is affected in various diseases, and whether manipulation of it will do any good (or harm).
Exciting times.
Chemiotics II 