Research

Our Goal: To decipher the molecular and cellular mechanisms underlying neural plasticity.

   Virtually every neural circuit in the mammalian forebrain incorporates local inhibitory interneurons that tune activity of their postsynaptic partners. While vastly outnumbered by principal excitatory cells, these interneurons play key roles in many facet of the brain function; from the processing of sensory information to the performance of complex cognitive tasks. 

     

     Similarly to their excitatory counterpart, the inhibitory cell population undergo perpetual experience-driven remodeling of their connection throughout life and this plasticity is essential for shaping their network during development as well as for learning, and acquisition of memory in adult. Increasing evidences suggest that maladaptive plasticity mechanisms lead to the alteration of the inhibitory network and ultimately to circuit dysfunction that may contribute to a broad spectrum of neurological disorders in humans.

     A major challenge of dissecting the principles of inhibitory network plasticity is the diversity of the interneuron population. There are a myriad of inhibitory subtypes that exhibit unique molecular profiles, morphologies, innervation patterns, and physiological properties. Taking advantage of genetic manipulations in mice with contemporary viral delivery methods we focus our research on inhibitory Parvalbumin expressing basket cells (PV). Our previous work shed light on a new form of plasticity that regulates the branching pattern of their axons in response to change in the excitatory inputs. Using multidisciplinary approach that combines chemical- and light-activated receptors and channels with electrophysiological and imaging readouts, we investigate molecular and cellular mechanisms regulating PV synapse formation and their structural plasticity.

     

     Our major endeavor aims at addressing fundamental questions of how GABAergic neurons shape a coherent inhibitory network during development and how it is adjusted in response to experience. Ultimately we wish to identify genes whose function are critical for appropriate adaptive plasticity in mice as we believe it will set the premise to link genetic predispositions with the etiology of neurodevelopmental diseases and improve our understanding of the pathophysiology of such disorders in humans.

Research Overview

Simon Pieraut

Featured: Firing of inhibitory PV interneurons projecting into the CA2 of the hippocampus 

 
 

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University of Nevada, Reno