Neocortical long-range inhibition for learning and memory

Project description

The ability to learn from experience and remember one’s past is one of the most fundamental and fascinating functions of the brain that is also a central element of individual and collective human identity. A mechanistic understanding of memory has implications reaching from treatment of memory disorders to artificial intelligence and efficient hard- and software design. While by now we have a tolerable understanding of how local circuits implement the plastic changes that underlie learning and memory, brain areas do not function in isolation. In fact, it is precisely the extreme degree of neuronal interconnectivity that makes brain research such a fascinating challenge. Therefore, the critical next step in learning and memory research is to dissect how long-range interactions between different brain areas contribute to, and interact with, local plasticity to enable functional circuit plasticity. Neocortical layer 1 (L1) receives diverse long-range excitatory inputs, many of which are known to be important for learning. However, my host lab has recently found that the zona incerta (ZI) – a subthalamic nucleus – sends long-range inhibitory (LRI) projections to L1 of the auditory cortex (ACx). Whether and how LRI contributes to memory encoding mechanisms in neocortical circuits is completely unknown. Here I outline a strategy to dissect how LRI projections from the ZI to L1 ACx contribute to learning and memory, using a combination of cutting-edge in vivo imaging and recording techniques in conjunction with associative fear conditioning, optogenetic manipulations, viral tracing, genetic markers and slice recordings in mice. This multidisciplinary investigation will reveal important insights into how long-range interactions between brain areas contribute to learning and memory. Moreover, successful completion of this project, and rigorous training in other aspects of academic life, will provide the ideal stepping stone for my transition to scientific independence.