Causal evidence for the behavioral impact of oscillations in neocortex and hippocampus

Abstract

Neuroscientists hold widely divergent opinions on the behavioral relevance of oscillatory brain states. Some consider them to be a side effect of anatomical connectivity, with little or no role in guiding action. Others view them as a fundamental feature of the network states that underlie perception and cognition. In this thesis, I take a systematic approach to studying two of the most prominent types of oscillations,'gamma rhythms in the neocortex (30-80 Hz) and theta rhythms in the hippocampus (4-12 Hz). In both cases, I use light-gated ion channels to manipulate spike activity on a cycle-by-cycle basis in awake, behaving mice. By rhythmically stimulating fast-spiking interneurons in somatosensory cortex, I can emulate the activity patterns that define gamma oscillations under natural conditions. Emulating gamma enhances the detection of threshold-level vibrissae deflections, analogous to the behavioral effects of shifting attention. By triggering stimulation of fast-spiking interneurons in the hippocampus on peaks and troughs of endogenous rhythms, I can reduce spike activity at specific phases of theta. In the context of a spatial navigation task, I find that the ability of inhibition to enhance decision-making accuracy depends on both the theta phase and the task segment in which it occurs. Both of these experiments provide novel causal evidence for the behavioral impact of oscillations, which offers a much more compelling argument for their utility than traditional correlative measures. Finally, I present a new platform for extracellular electrophysiology. This platform, called Open Ephys, makes the closed-loop experiments that are ideal for studying oscillations accessible to a wider audience.