How can it be like that?

The following quote is from an old book on LISP programming (Let’s Talk LISP) by Laurent Siklossy.“Remember, if you don’t understand it right away, don’t worry. You never learn anything, you only get used to it.”

Unlike quantum mechanics, where Feynman warned never to ask ‘how can it be like that’, those of us in any area of biology should always  be asking ourselves that question.  Despite studying the brain and its neurons for years and years and years, here’s a question I should have asked myself (but didn’t, and as far as I can tell no one has until this paper [ Proc. Natl. Acad. Sci. vol. 117 pp. 4368 – 4374 ’20 ] ).

It’s a simple enough question.  How does a neuron know what receptor to put at a given synapse, given that all neurons in the CNS have both excitatory and inhibitory synapses on them. Had you ever thought about that?  I hadn’t.

Remember many synapses are far away from the cell body.  Putting a GABA receptor at a glutamic acid synapse would be less than useful.

The paper used a rather bizarre system to at least try to answer the question.  Vertebrate muscle cells respond to acetyl choline.  The authors bathed embryonic skeletal muscle cells (before innervation) with glutamic acid, and sure enough glutamic acid receptors appeared.

There’s a lot in the paper about transcription factors and mechanism, which is probably irrelevant to the CNS (muscle nuclei underly the neuromuscular junction).   Even if you send receptors for many different neurotransmitters everywhere in a neuron, how is the correct one inserted and the rest not at a given synapse.

I’d never thought of this.  Had you?

 

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Comments

  • Mark Thorson  On March 4, 2020 at 12:52 am

    Even if you send receptors for many different neurotransmitters everywhere in a neuron, how is the correct one inserted and the rest not at a given synapse.

    Maybe they are all inserted and the ones that never see a neurotransmitter get tagged for recycling? If the tag falls off when the neurotransmitter binds, you could have one enzyme that tags every receptor and another that carts away anything that has a tag on it. On average, the receptors that get used lose their tags, while the unused receptors are carted away. When unused receptors start piling up in the cell body, they may inhibit their own synthesis because the cell already has too many of them.

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