Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, February 2011.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Cataloged from student-submitted PDF version of thesis.Includes bibliographical references.Inhibitory interneurons are thought to play a crucial role in several features of neocortical processing, including dynamics on the timescale of milliseconds. Their anatomical and physiological characteristics are diverse, suggesting that different types regulate distinct aspects of neocortical dynamics. Interneurons expressing parvalbumin (PV) and somatostatin (SOM) form two non-overlapping populations. Here, I describe computational, correlational (neurophysiological) and causal (optogenetic) studies testing the role of PV and SOM neurons in dynamic regulation of sensory processing. First, by combining extra- and intracellular recordings with optogenetic and sensory stimulation and pharmacology, we have shown that PV cells play a key role in the generation of neocortical gamma oscillations, confirming the predictions of prior theoretical and correlative studies. Following this experimental study, we used a biophysically plausible model, simulating thousands of neurons, to explore mechanisms by which these gamma oscillations shape sensory responses, and how such transformations impact signal relay to downstream neocortical areas. We found that the local increase in spike synchrony of sensory-driven responses, which occurs without decreasing spike rate, can be explained by pre- and post-stimulus inhibition acting on pyramidal and PV cells. This transformation led to increased activity downstream, constituting an increase in gain between the two regions. This putative benefit of PV-mediated inhibition for signal transmission is only realized if the strength and timing of inhibition in the downstream area is matched to the upstream source. Second, we tested the hypothesis that SOM cells impact a distinct form of dynamics, sensory adaptation, using intracellular recordings, optogenetics and sensory stimulation. In resting neocortex, we found that SOM cell activation generated inhibition in pyramidal neurons that matched that seen in in-vitro studies. Optical SOM cell activation also transformed sensory-driven responses, decreasing evoked activity. In adapted responses, optical SOM cell inactivation relieved the impact of sustained sensory input, leading to increased membrane potential and spike rate. In contrast, SOM cell inactivation had minimal impact on sensory responses in a non-adapted neocortex, supporting the prediction that this class of interneurons is only recruited when the network is in an activated state. These findings present a previously unappreciated mechanism controlling sensory adaptation.by Ulf Knoblich.Ph.D
