The Age of Enlightenment: Evolving Opportunities in Brain Research Through Optical Manipulation of Neuronal Activity

Optical manipulation of neuronal activity has rapidly developed into the most powerful and widely used approach to study mechanisms related to neuronal connectivity over a range of scales. Since the early use of single site uncaging to map network connectivity, rapid technological development of light modulation techniques has added important new options, such as fast scanning photostimulation, massively parallel control of light stimuli, holographic uncaging, and two-photon stimulation techniques. Exciting new developments in optogenetics complement neurotransmitter uncaging techniques by providing cell-type specificity and in vivo usability, providing optical access to the neural substrates of behavior. Here we review the rapid evolution of methods for the optical manipulation of neuronal activity, emphasizing crucial recent developments

"The great mixing machine”: multisensory integration and brain-breath coupling in the cerebral cortex.

It is common to distinguish between “holist” and “reductionist” views of brain function, where the former envisions the brain as functioning as an indivisible unit and the latter as a collection of distinct units that serve different functions. Opposing reductionism, a number of researchers have pointed out that cortical network architecture does not respect functional boundaries, and the neuroanatomist V. Braitenberg proposed to understand the cerebral cortex as a “great mixing machine” of neuronal activity from sensory inputs, motor commands, and intrinsically generated processes. In this paper, we offer a contextualization of Braitenberg’s point, and we review evidence for the interactions of neuronal activity from multiple sensory inputs and intrinsic neuronal processes in the cerebral cortex. We focus on new insights from studies on audiovisual interactions and on the influence of respiration on brain functions, which do not seem to align well with “reductionist” views of areal functional boundaries. Instead, they indicate that functional boundaries are fuzzy and context dependent. In addition, we discuss the relevance of the influence of sensory, proprioceptive, and interoceptive signals on cortical activity for understanding brain-body interactions, highlight some of the consequences of these new insights for debates on embodied cognition, and offer some suggestions for future studies

High-Precision, Three-Dimensional Tracking of Mouse Whisker Movements with Optical Motion Capture Technology

The mystacial vibrissae or whiskers in rodents are sensitive tactile hairs emerging from both sides of the face. Rats and mice actively move these whiskers during exploration. The neuronal mechanisms controlling whisker movements and the sensory representation of whisker tactile information are widely studied as a model for sensorimotor processing in mammals. Studies of the natural whisker movement patterns during exploration and tactile examination are still in their early stages. Tracking the movements of whiskers is technically challenging as they move relatively fast and are very thin, particularly in mice. Existing systems detect light-beam interruptions by the whiskers or use high-speed video to track whisker movements in one or two-dimensions. Here we describe a method for tracking the movements of mouse whiskers in three-dimensions (3D) using optical motion capture technology (OMCT). OMCT tracks the movements of small retro-reflective markers attached to whiskers of a head-fixed mouse with a spatial resolution of <0.5 mm in all 3D and a temporal resolution of 5 ms (200 fps). The system stores the 3D coordinates of the marker's trajectories onto hard disk allowing a detailed analysis of movement trajectories bilateral coordination. The described method currently uses the minimum of two tracking cameras, which requires head-fixation for reliable tracking

Respiratory rhythms of the predictive mind

Respiratory rhythms sustain biological life, governing the homeostatic exchange of oxygen and carbon dioxide. Until recently however, the influence of breathing on the brain has largely been overlooked. Yet new evidence demonstrates that the act of breathing exerts a substantive, rhythmic influence on perception, emotion, and cognition, largely through the direct modulation of neural oscillations. Here we synthesize these findings to motivate a new predictive coding model of respiratory brain coupling, in which breathing rhythmically modulates both local and global neural gain, to optimize cognitive and affective processing. Our model further explains how respiratory rhythms interact with the topology of the functional connectome, and we highlight key implications for the computational psychiatry of disordered respiratory and interoceptive inference

Breathing as a Fundamental Rhythm of Brain Function

Ongoing fluctuations of neuronal activity have long been considered intrinsic noise that introduces unavoidable and unwanted variability into neuronal processing, which the brain eliminates by averaging across population activity (Georgopoulos et al., 1986; Lee et al., 1988; Shadlen and Newsome, 1994; Maynard et al., 1999). It is now understood, that the seemingly random fluctuations of cortical activity form highly structured patterns, including oscillations at various frequencies, that modulate evoked neuronal responses (Arieli et al., 1996; Poulet and Petersen, 2008; He, 2013) and affect sensory perception (Linkenkaer-Hansen et al., 2004; Boly et al., 2007; Sadaghiani et al., 2009; Vinnik et al., 2012; Palva et al., 2013). Ongoing cortical activity is driven by proprioceptive and interoceptive inputs. In addition, it is partially intrinsically generated in which case it may be related to mental processes (Fox and Raichle, 2007; Deco et al., 2011). Here we argue that respiration, via multiple sensory pathways, contributes a rhythmic component to the ongoing cortical activity. We suggest that this rhythmic activity modulates the temporal organization of cortical neurodynamics, thereby linking higher cortical functions to the process of breathing

Thalamocortical Communication in the Awake Mouse Visual System Involves Phase Synchronization and Rhythmic Spike Synchrony at High Gamma Frequencies

In the neocortex, communication between neurons is heavily influenced by the activity of the surrounding network, with communication efficacy increasing when population patterns are oscillatory and coherent. Less is known about whether coherent oscillations are essential for conveyance of thalamic input to the neocortex in awake animals. Here we investigated whether visual-evoked oscillations and spikes in the primary visual cortex (V1) were aligned with those in the visual thalamus (dLGN). Using simultaneous recordings of visual-evoked activity in V1 and dLGN we demonstrate that thalamocortical communication involves synchronized local field potential oscillations in the high gamma range (50–90 Hz) which correspond uniquely to precise dLGN-V1 spike synchrony. These results provide evidence of a role for high gamma oscillations in mediating thalamocortical communication in the visual pathway of mice, analogous to beta oscillations in primates