The cerebral cortex continuously adapts through learning and changes in sensory experience. A major goal of neuroscience is to understand the cellular and synaptic plasticity mechanisms that allow behavior to adapt to a changing environment. Remarkably, neural circuits maintain stable activity despite ongoing adaptive changes in synaptic strength and connectivity. Recent work has revealed multiple homeostatic plasticity mechanisms that maintain neural firing rates within an optimum range. However, it is not well understood how brain circuits maintain homeostasis in different brain regions and across different time scales.

In primary sensory cortex, changes in sensory input drive adaptive changes in cortical representations. Broadly, depriving a set of sensory inputs rapidly weakens neural responses to those inputs and gradually strengthens spared inputs. Recent studies show that deprivation also triggers rapid plasticity in inhibitory circuits that could stabilize neural activity despite ongoing weakening of deprived inputs. Chapter 2 investigates the cellular and circuit mechanisms that underlie this rapid plasticity of inhibition in the superficial layers of rodent primary somatosensory cortex (S1). This study shows that 1-day whisker deprivation weakens inhibition in layer (L) 2/3 pyramidal neurons by decreasing the intrinsic excitability of L2/3 parvalbumin-positive (PV) interneurons near spike threshold. Deprivation reduces PV spike threshold through an increase in voltage-gated potassium conductances. These findings demonstrate that activity in sensory cortex is rapidly stabilized through plasticity of PV intrinsic excitability.

Often, a single sensory manipulation drives multiple cellular and circuit changes with distinct temporal components. In cortical inhibitory circuits, the time course of plasticity is not well understood. Building on the studies in Chapter 2, we hypothesized that additional plasticity mechanisms may be recruited in L2/3 PV neurons in response to different time scales of whisker deprivation. In Chapter 3, we test this idea by extending the the duration of whisker deprivation to 3 days and asking whether changes in L2/3 PV circuits are consistent with those observed after 1 day of deprivation. We find that 3-day deprivation also decreases PV intrinsic excitability, but through a different mechanism than 1-day deprivation. Deprivation strengthens the medium afterhyperpolarization (mAHP) without affecting spike threshold. Thus, experience-dependent plasticity of cortical PV circuits involves a succession of distinct components.