Synaptic mechanisms of auditory memory

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DESCRIPTION (provided by applicant): Primary sensory cortices not only analyze sensory information but also store information about learned sensory experiences. The auditory cortex (ACx) acquires and retains specific memory traces about the behavioral significance of selected sounds. During learning, the tuning properties of ACx neurons undergo activity-dependent changes. This cortical map plasticity, which is believed to be a substrate of auditory memory, is characterized by the facilitation of responses to behaviorally important tones at the expense of other frequencies. In mature animals, it can be induced by pairing selected tones with activation of cholinergic projections from the nucleus basalis. In young animals, cortical map plasticity in the ACx can be induced by passive enrichment of the environment with a certain sound. Cellular mechanisms of cortical map plasticity are unknown. In this project, we will test our hypothesis that bidirectional changes in cortical responses during learning can be encoded by synaptic mechanisms such as long-term potentiation (LTP) and long-term depression (LTD) at thalamocortical (TC) excitatory synapses.TC projections provide the major ascending sensory input to the neocortex and contribute to the formation of cortical maps in sensory cortices. Thus, synaptic plasticity at TC synapses should greatly influence cortical map plasticity in the ACx. However, it has been postulated that LTP and LTD at TC synapses are limited to the early postnatal period that in rodents corresponds to the first several postnatal days. This suggests that TC synaptic plasticity cannot be a substrate of cortical map plasticity and perceptual memory in mature animals. Recently, we showed that TC synaptic plasticity is not lost in the mature ACx; instead, it acquires gating mechanisms during postnatal development that can be released by activating cholinergic receptors on presynaptic terminals of TC projections. Once gating is released, LTP and LTD can occur at TC synapses of animals aged far beyond the early critical period. Using 2-photon imaging of synaptic function, 2-photon glutamate uncaging, and whole-cell recordings in TC slices from mature animals, we recently identified novel cellular and molecular mechanisms of LTD and LTP at TC synapses. We also began characterizing the gating mechanisms. Here, we propose to test our hypothesis that TC synaptic plasticity underlies cortical map plasticity in mature animals. Using electrophysiologic mapping in vivo, we will determine whether mechanisms that affect LTP and LTD at TC synapses also affect cortical map plasticity in the ACx. Using imaging and optogenetic, molecular, and electrophysiological tools, we will further characterize the mechanisms of TC synaptic plasticity. Identifying these mechanisms will expand our understanding of cortical map plasticity in the ACx. Knowledge gained from these studies will provide the basis for future elucidation of the cellular and molecular mechanisms of auditory memory.