The synapse is not a oneway street

Back in the day when I was a Med student at Penn ’62 – ’66 and not that far away from the first programmable computer (The ENIAC) built at Penn in the 40’s using vacuum tubes (the transistor was far in the future) we ‘knew’ that information flowed across the synapse in one way, the same way that current flowed just one way in vacuum tubes.  Our conception of the synapse that way was that the presynaptic side was the master and the post synaptic side was the slave.  It worked well as a model of how the brain computes things initially, with current flowing through boolean diagrams of neurons.  It still works pretty well today with neural nets where information flows pretty much in one way through the layers of ‘neurons’.

Well that’s not the way we think about the synapse today, and an excellent paper [ Neuron vol. 110 pp. 4144 – 4161 ’22 ] brings it home.  It shows that the same axon releases its neurotransmitter (glutamic acid) differently depending on what post-synaptic neuron it is innervating.

When the axon from a pyramidal neuron synapses on a fast spiking parvalbumin containing interneuron there is a high probability of glutamic acid release with each nerve impulse (action potential).  The same axon when innervating another type of interneuron (containing somatostatin), the release probability is 10fold lower.

So it all depends on what is being innervated.  The somatostatin interneuron expresses Elfn1 (you don’t want to know what this acronym is for) which activates a presynaptic receptor for glutamic acid (mGluR7) which reduces synaptic release probability.

This isn’t seen in the parvalbumin interneurons.  Essentially the post-synaptic neuron is partially controlling the presynaptic neuron.

The work was done in the hippocampus, where the neuroanatomy and neurochemistry has been worked out better than most areas of the brain.  How widespread differential release of transmitter is, will have to wait until we understand the neuroanatomy of other brain areas better.

If you want to read about the building of the ENIAC at Penn, have a look at the following post — https://luysii.wordpress.com/2022/09/18/book-review-proving-ground-kathy-kleiman/.  Trigger warning — the women who figured out how to program the ENIAC were not treated particularly well but decades later received the recognition they deserved.