Biochemical & synaptic substrates of learning

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DESCRIPTION (provided by applicant): The proposed studies investigate well-established molecular and anatomical substrates of synaptic plasticity as they relate to a natural instance of age-regulated sensorimotor learning, the development of avian song. Vocal learning in birds involves the encoding of a specific sensory stimulus (the song model) and a refinement of vocal motor patterns to emulate the acquired model. Previous studies suggest that birdsong learning entails a form of NMDA receptor (MDAR)-dependent synaptic plasticity within discrete regions of the anterior forebrain. Such plasticity frequently depends upon the phosphorylation (activation) of calcium calmodulin dependent protein kinase II (CaMKII), and recent work reveals that brief exposure to song during the sensitive learning period phosphorylates CaMKII within this forebrain circuit. Moreover, the strength of this song-induced signal relates to stimulus conditions that favor learning. Quantitative immunoblots (IB) will be used to determine if this song-induced signal occurs in other song regions, and if it is accompanied by phosphorylation of CREB (cAMP response element binding protein), an event involved in the stabilization of synaptic strengthening. Also, the separate and interactive effects of vocal practice on these cellular signals will be assessed, and immunocytochemistry will be used to identify the neuronal subpopulations involved in their expression. Intercranial pharmacological manipulations will be used to determine if the song-induced activation of CaMKII is necessary for normal song development. The final experiment focuses on synaptic rearrangement, a process believed to underlie long-term representations of early experience. By delaying the timing of song learning beyond the normal close of the sensitive period for song learning, the relationship between spine pruning and song learning will be tested. By evaluating whether biochemical cascades and synaptic changes long implicated in neural plasticity also contribute to avian vocal learning, the work will clarify how these processes relate to naturally-occurring behavioral plasticity. In addition, the studies will advance our understanding of how the cognitive processes that comprise vocal learning are distributed and executed at the neural systems level.