Project 460078

Recognizing and responding to novelty is critical for everyday life, and many neural disorders exhibit novelty-related behavioural manifestations. As such, understanding how novelty stimuli are coded in the brain is important for both fundamental and clinical neuroscience. Our preliminary data has uncovered a rare, atypical neuron type in the hippocampus that seems uniquely poised - at molecular, cellular, circuit, and behavioural levels - to produce sustained cellular "memory" of transiently encountered novel stimuli. Capitalizing on these preliminary findings, our laboratory will combine cutting-edge high-throughput technologies and big data analysis in mice to uncover how novelty is coded and stored in the brain. To do so, we will begin by using brain slice preparations, and examine whether these atypical neurons have specialized properties that can amplify and transmit slow signals associated with novel stimuli. To complement these experiments, we will perform cellular imaging during behaviour, and manipulate atypical neurons and their molecules to identify neural mechanisms that drive novelty-associated behaviour. Finally, measuring the expression of every gene in the genome for individual cells, we will establish a neural "blueprint" of the molecules and cells that receive signals from these atypical neurons. We will then study these downstream neurons to understand how distinct layers of processing in the brain acts to transform and transmit novelty-related signals. Our research here provides multidisciplinary insight into the brain's map of novelty and familiarity, integrated across molecular, cellular, circuit, and behavioural neuroscience. This will provide a comprehensive understanding of the basic biology of novelty recognition and response. In the long term, such results will generate a framework by which recognition and novelty-associated impairments can be understood and potentially treated.