While plasticity in excitatory circuits in cerebral cortex is well understood, the mechanisms and functions of inhibitory circuit plasticity remain unclear. Different inhibitory interneuron subtypes are likely to have different roles in cortical plasticity. In sensory cortex, parvalbumin (PV) interneurons exhibit rapid experience-dependent plasticity that homeostatically stabilizes mean cortical firing rate, and vasoactive intestinal peptide (VIP) interneurons disinhibit pyramidal (PYR) cells to promote plasticity of sensory representations. In contrast, the role of somatostatin (SOM) interneurons are poorly understood. SOM cells contribute to recurrent and cross-columnar inhibition, especially during sustained stimuli, and inhibit both PYR dendrites and PV cells. SOM cells have been proposed to act as a gate for plasticity and learning, but no consensus exists on how they accomplish this. Current theories are based on stable function of SOM cells in generating PYR dendritic inhibition, or in inhibiting PV cells. Whether sensory experience alters SOM circuit function is unknown and could be an important part of understanding SOM contribution to overall plasticity. I will study experience-dependent changes in SOM circuits in L2/3 of mouse primary somatosensory cortex (S1). I hypothesize that SOM cells dominate cross-columnar pathways, whereas PV cells dominate local recurrent inhibition in the home column. I propose that SOM cells gate plasticity through direct inhibition of PYR cells that is transiently strengthened following whisker deprivation. This is fundamentally distinct from PV circuits, which weaken in response to deprivation to maintain stable cortical firing rates. To test this hypothesis, I will optogenetically activate feedforward, local recurrent, and cross-columnar circuits in S1, and test how whisker deprivation alters inhibition on these pathways. Using targeted patch clamp recordings, I will test how SOM and PV circuits are specifically changed to mediate these effects. In dual whole-cell patch-clamp recordings, I will characterize changes in SOM<- >PYR unitary synaptic connections. I will also measure changes in intrinsic excitability of SOM cells that would contribute to any synaptic changes measured between PYR-SOM or SOM-PYR pairs. Understanding the plasticity of inhibitory circuits will advance our understanding of circuit function both in health and in pathological conditions. Circuit abnormalities and deficits in sensory have been reported in psychiatric and neurodevelopmental disorders such as schizophrenia and autism spectrum disorder. Understanding circuit function is critical for understanding circuit deficits and how these deficits lead to altered sensory perception in psychiatric conditions.

Public Health Relevance

Inhibitory neurons play diverse roles in cerebral cortex, but plasticity within inhibitory circuits remains poorly understood. This project focuses on somatostatin (SOM) interneurons, which have been proposed to gate plasticity in excitatory networks, however whether experience alters SOM circuits, and by what mechanisms, are unknown. I propose optogenetic and electrophysiological experiments to characterize SOM circuit plasticity, which will shed light on how different interneuron subtypes participate in cortical plasticity.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Postdoctoral Individual National Research Service Award (F32)
Project #
Application #
Study Section
Neurological Sciences Training Initial Review Group (NST)
Program Officer
David, Karen Kate
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Berkeley
Organized Research Units
United States
Zip Code