How Forebrain Dynamics within and Beyond Neurons Create Behavior

The forebrain evolved after vertebrates were able to perform complex perceptual tasks. Its added value is almost certainly in providing mammals the capability to optimally function beyond genetic programming, optimization that emerges from rapid and long-term time scale dynamics in this structure and with its interconnected networks. A canonical example of rapid time-scale neocortical dynamics occurs with behavioral allocation of attention, following which the sensitivity and specificity of neocortical neurons changes substantially, in ways that predict enhanced information processing. We study these dynamics and their meaning for information processing.

Central to our view is the conviction that non-neural systems play a crucial role in this optimal information processing. We believe that to understand how biology creates behavior requires going beyond neurons. We are pursuing this direction at a high level by initiating group conversations among experts, to determine the key concepts and next steps essential to understanding these systems (bioinfosystems.org).  At a local level, multiple lab projects are targeted to non-neural brain systems, such as the choroid plexus and vasculature. We are developing new tools to study these systems, and testing their role in behavior.

One area of focus in our lab has been testing the role of neocortical 'gamma' oscillations. Gamma oscillations are rhythmic activity patterns in the range from ~30-80 Hz that are increased in many neocortical areas during active processing, for example with the allocation of attention. The importance of this dynamic is a much fought over topic, with views ranging from the belief that these signals are key to consciousness perception, to the view that they are an ‘exhaust fume’ of computation, an epiphenomenal accident with no link to optimal sensory processing.

In initial mechanistic studies (Cardin et al., 2009 Nature; Cardin et al., 2010 Nat Protocols; Carlen et al., 2012 Mol Psych), we used optogenetics to causally test in vivo the hypothesis that synchronization of a specific type of interneuron, fast-spiking cells, was key to the expression of gamma. We found that a highly naturalistic and specific expression of gamma was generated by selective drive of this ‘FS’ cell class, in agreement with a wealth of prior computational and correlative studies. We have now used this specific form of control to test the hypothesis that induced FS-gamma can enhance detection performance (Siegle, Pritchett et al., 2014 Nat Neurosci). We found, and have recently extensively replicated (Shin, PhD Thesis) that specific emulation of FS-gamma by optogenetic drive predicts increased likelihood of correctly detecting a sensory input.

A critical puzzle in understanding the role of FS-gamma is the question of how these FS can both encode stimuli in real time (e.g., have sensory responses) and perpetuate a consistent local gamma oscillation. Our recent results show that a distinct group of FS exist in sensory neocortex whose gamma spiking robustly predicts successful perception, and that are not responsive to the outside world (Shin and Moore, 2019 Neuron). These findings indicate that this FS subgroup may play an independent role in network coordination crucial to the relay of information in the brain.