Coffee Mug: “keep the cell from building synapses bigger all willy-nilly.”

Could this be a feedback mechanism to keep a neuron from becoming strongly connected to too many other neurons?

If synaptic activity down-regulates ARC through the AMPA pathway and thereby inhibits synapse building, then a neuron with significant synaptic activity would be less available for forming new connections. (Dendrites and axons form a very dense cloud with potential for a vast number of synaptic connections. Only a small fraction of those potential connections are ever strengthened. See http://www.almaden.ibm.com/insti...te/ agenda.shtml. )

Imagine that a new concept is being formed and groups of neurons are being recruited to store the new concept. The new neuronal group would tie together pre-existing neuronal groups that hold associated concepts. E.g., a new object would have a shape, a color, a texture, an odor, a function, etc. So when all of those attribute concepts are stimulated, a collection of “candidate” neurons that link the concepts are stimulated. The new concept would be stored in the neurons that were most stimulated by the attribute links.

A long-term feedback mechanism that hindered building synapses could bias the selection of “candidate” neurons so that only that were sparsely connected would store the new concept. Then new concepts wouldn’t overwrite old concepts.

I agree that it seems like AMPARs are working as negative feedback. They may not even be feeding back so much as just acting as a dampener, to set the tone such that it is difficult to achieve a long-term plasticity event. Making the threshold high for intiating plasticity would create a more stable system. It would be good indeed to avoid too much overwrite.

it might be important to note that the conditions of these experiments are pretty far removed from the reality in a brain.. we will never see this huge jump in BDNF-induced Arc levels in vivo because there won't be an AMPA receptor antagonists lying around.. AMPA receptors are usually consistently being activated.. so i could see them as a sort of constitutive dampener..

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