Mechanisms of stimulus-induced network focusing

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Project Summary Large-scale recordings are discovering that individual neurons in sensory, cognitive, and motor networks often participate variably, even when presented with identical inputs. The reason for such variability is unclear, and an active topic of debate in the field. Does it reflect randomness in neuronal participation, or is it an adaptive feature that plays an essential role in healthy brain function? The scientific premise of this application is the latter—that variably participating neurons reflect the operation of a “focusing” mechanism innate to many networks that allows them to rapidly and flexibly rearrange which neurons are called upon to process specific information in the context of the moment. This hypothesis emerged unexpectedly from our large-scale recordings of the rhythmic escape swim network of the marine mollusk Tritonia diomedea. We were surprised to discover that during the initial seconds of responding to an unexpected aversive sensory input, Tritonia's swim motor program rapidly tunes itself, pulling many initially-silent neurons into the bursting population and driving others out, apparently optimizing itself for escape. In this Tritonia case, the “focused” state is then maintained for several minutes, enabling a stronger, faster-onset motor program should the same stimulus recur. Many studies in vertebrates have reported rapid growth in the size of responding networks with repeated stimulation, but the mechanisms and purpose of such phenomena are poorly understood. This project's goal is to uncover the mechanisms underlying what may be an important versatility process for healthy function in many brain networks—one that allows them to rapidly re-allocate neurons to suit a specific context, and then hold that focused state for a sustained period of time. The project has 2 Specific Aims: Aim 1 will map the re-allocating neurons and address several issues regarding the phenomenology of this poorly understood network focusing process. Aim 2 will determine the cellular mechanisms driving the rapid re- allocation of neurons into and out of the bursting escape swim network as it focuses. The principles of rapid network focusing to be investigated here may promote novel approaches for treating or preventing declines in cognitive function in aging and disease.