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

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

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

Born to Cry: A Genetic Dissection of Infant Vocalization

Infant vocalizations are one of the most fundamental and innate forms of behavior throughout avian and mammalian orders. They have a critical role in motivating parental care and contribute significantly to fitness and reproductive success. Dysregulation of these vocalizations has been reported to predict risk of central nervous system pathologies such as hypoxia, meningitis, or autism spectrum disorder. Here, we have used the expanded BXD family of mice, and a diallel cross between DBA/2J and C57BL/6J parental strains, to begin the process of genetically dissecting the numerous facets of infant vocalizations. We calculate heritability, estimate the role of parent-of-origin effects, and identify novel quantitative trait loci (QTLs) that control ultrasonic vocalizations (USVs) on postnatal days 7, 8, and 9; a stage that closely matches human infants at birth. Heritability estimates for the number and frequency of calls are low, suggesting that these traits are under high selective pressure. In contrast, duration and amplitude of calls have higher heritabilities, indicating lower selection, or their importance for kin recognition. We find suggestive evidence that amplitude of infant calls is dependent on the maternal genotype, independent of shared genetic variants. Finally, we identify two loci on Chrs 2 and 14 influencing call frequency, and a third locus on Chr 8 influencing the amplitude of vocalizations. All three loci contain strong candidate genes that merit further analysis. Understanding the genetic control of infant vocalizations is not just important for understanding the evolution of parent–offspring interactions, but also in understanding the earliest innate behaviors, the development of parent–offspring relations, and the early identification of behavioral abnormalities

Shaping Diversity Into the Brain’s Form and Function

The brain contains a large diversity of unique cell types that use specific genetic programs to control development and instruct the intricate wiring of sensory, motor, and cognitive brain regions. In addition to their cellular diversity and specialized connectivity maps, each region’s dedicated function is also expressed in their characteristic gross external morphologies. The folds on the surface of the cerebral cortex and cerebellum are classic examples. But, to what extent does structure relate to function and at what spatial scale? We discuss the mechanisms that sculpt functional brain maps and external morphologies. We also contrast the cryptic structural defects in conditions such as autism spectrum disorders to the overt microcephaly after Zika infections, taking into consideration that both diseases disrupt proper cognitive development. The data indicate that dynamic processes shape all brain areas to fit into jigsaw-like patterns. The patterns in each region reflect circuit connectivity, which ultimately supports local signal processing and accomplishes multi-areal integration of information processing to optimize brain functions