Gina Turrigiano, Department of Biology and Neuroscience Program, Brandeis University, USA
The ups and downs of homeostatic plasticity
Neocortical networks must generate and maintain stable activity patterns despite perturbations induced by learning and experience- dependent plasticity. There is abundant theoretical and experimental evidence that network stability is achieved through homeostatic plasticity mechanisms that adjust synaptic and neuronal properties to stabilize some measure of average activity, and this process has been extensively studied in primary visual cortex (V1), where chronic visual deprivation induces an initial drop in activity and ensemble average firing rates (FRs), but over time activity is restored to baseline despite continued deprivation. Here I discuss recent work from the lab in which we followed this FR homeostasis in individual V1 neurons in freely behaving animals during a prolonged visual deprivation/eye-reopening paradigm. We find that - when FRs are perturbed by manipulating sensory experience - over time they return precisely to a cell-autonomous set-point. Finally, we find that homeostatic plasticity depends critically on normal levels of Shank3 (which is strongly associated with human Autism and intellectual disability), and is gated by changes in Shank3 phosphorylation. Loss of Shank3 in rodent models results in a breakdown of FRH within V1, and disrupts vision-dependent learning. These data suggest that loss of homeostatic plasticity is one primary cause of circuit disregulation in rodent models of Autism Spectrum Disorder. Together these studies illuminate the role of stabilizing plasticity mechanisms in the ability of neocortical circuits to recover robust function following challenges to their excitability through altered sensory experience and learning.
Gina Turrigiano received her BA from Reed College in 1984 and her PhD from UC San Diego in 1990. She trained as a postdoc with Eve Marder at Brandeis University before joining the faculty in 1994, where she is now the Levitan Professor of Vision Science in the Department of Biology. Her work has focused on identifying the cellular and circuit mechanisms that stabilize neural circuit function, especially the discovery and characterization of homeostatic forms of synaptic and intrinsic plasticity. She has received numerous awards for this research, including a MacArthur fellowship, an NIH director’s pioneer award, and the HFSP Nakasone Award. She is a fellow of AAAS and a member of the American Academy of Arts and Sciences and the National Academy of Sciences.