Nicholas J. Priebe

We readily perceive stereoscopic depth in correlated random dot stereograms (RDS), in which every dot presented to one eye has a matching dot in the other eye. In contrast, anti-correlated RDS, in which corresponding dots have opposite contrast polarity between the two eyes, do not evoke a perception of depth. Nevertheless, anti-correlated RDS still generate local same-polarity matches within the receptive fields of individual neurons. Inhibitory circuitry has been proposed to suppress these false matches and thereby prevent the perception of illusory depth. To investigate how inhibitory circuits in visual cortex contribute to this process, we measured disparity selectivity to correlated and anti-correlated RDS in two major classes of inhibitory neurons in mice: parvalbumin-expressing (PV+) and somatostatin-expressing (SST+) neurons. We found that the disparity tuning of PV+ neurons was highly correlated with the average activity of surrounding neurons. In contrast, the disparity tuning of SST+ neurons was poorly predicted by local population activity, suggesting that PV+ and SST+ neurons integrate excitatory inputs through distinct mechanisms. Optogenetic suppression of PV+ or SST+ neurons further revealed divergent functional roles. Although both cell types contributed to sharpening selectivity for correlated RDS, only SST+ neurons reduced selectivity for anti-correlated RDS. These findings suggest that PV+ and SST+ circuits both enhance responses to correct binocular matches in correlated RDS, whereas SST+ circuits contribute to suppressing false matches in anti-correlated RDS.

Our perception of the world depends on a complex interplay between external sensory inputs and our internal states. How and where in the brain these interactions are implemented remain poorly understood. To address these questions, we measured membrane potential (V_m) of single V1 neurons in macaque monkeys performing a reaction-time visual detection task. Here we show that most V1 neurons gradually depolarize in preparation for target onset, and that variations in this buildup are correlated with the monkey's reaction times. Further, we show that fluctuations in V_m after target onset are correlated with choice, and that these covariations strongly depend on the location and contrast of the target. Finally, we show that a simple computational model with fluctuating multiplicative gain can account for our results. Thus, the surprising covariations between V_m of single V1 neurons and behavior are implemented by internal-state-related nonlinear modulations operating at, or before, V1.

Natural environments contain behaviorally relevant information along many stimulus dimensions, each of which sensory systems must encode in order to guide behaviors. For example, the mammalian visual cortex encodes features of visual scenes such as spatial information related to object identity and temporal information about the motion of those objects in space. In order to reliably encode these behaviorally relevant visual features, neural representations should be robust to changes in environmental conditions. Further, information about changes in environmental conditions, such as the luminance changes that occur over the course of a day, is also important for guiding behaviors. In this study, we asked whether mouse primary visual cortex (V1) jointly represents the spatial properties of visual stimuli along with changes in the mean luminance of the visual scene. We find that while V1 neurons, in mice of either sex, encode spatial aspects of visual information in an invariant manner across luminance conditions, the V1 population response also contains a robust representation of luminance. Importantly, V1 populations encode changes in stimulus orientation and mean luminance along orthogonal axes in the neural response space, such that a change in one stimulus variable is encoded independently from the other.

The thalamus performs a critical role in sensory processing by gating the flow of sensory information to the neocortex and directing sensory-driven behaviors; functions which are disrupted in people with autism spectrum disorders (ASD). We have identified cellular changes in thalamic neurons in a mouse model of Fragile X syndrome (FX), the leading monogenic cause of ASD, that alter how the thalamus transmits sensory information to neocortical circuits. In awake animals, thalamic relay cells gate input by shifting between two firing modes: burst and tonic. Relay cells in FX mice, however, do not shift between these modes and instead operate primarily in the tonic mode. We demonstrate that the lack of burst mode firing is caused by a shift in the voltage sensitivity for the Ca ²⁺ -dependent low threshold spike, which underlies normal burst firing.

We describe a chamber system to perform imaging, electrophysiology, and optogenetic stimulation in awake and anesthetized marmosets. We developed this low-profile chamber design to be able to access the underlying tissue when needed or to leave it sealed for long periods. Such accessibility is useful to maintain chamber clarity as well as perform viral or drug injections at different time points. The chamber is flexible as either optical or electrophysiological recording can be performed in the same chamber by exchanging chamber inserts. The design provides an easy approach to day-to-day stable neural recordings that was developed for marmosets and can be extended to other species.

Cortical neurons are characterized by their variable spiking patterns. We challenge prevalent theories for the origin of spiking variability. We examine the specific hypothesis that cortical synchrony drives spiking variability in vivo . Using dynamic clamp, we demonstrate that intrinsic neuronal properties do not contribute substantially to spiking variability, but rather spiking variability emerges from weakly synchronous network drive. With large-scale electrophysiology we quantify the degree of synchrony and its time scale in cortical networks in vivo . We demonstrate that physiological levels of synchrony are sufficient to generate irregular responses found in vivo . Further, this synchrony shifts over timescales ranging from 25 to 200 ms, depending on the presence of external sensory input. Such shifts occur when the network moves from spontaneous to driven modes, leading naturally to a decline in response variability as observed across cortical areas. Finally, while individual neurons exhibit reliable responses to physiological drive, different neurons respond in a distinct fashion according to their intrinsic properties, contributing to stable synchrony across the neural network.

Our perception of the world depends on a complex interplay between external sensory inputs and our internal states. How and where in the brain the interactions between internal states and sensory inputs are implemented remain open questions. To study the neural basis of these interactions, we used whole-cell recording to measure membrane potential (Vm) of single V1 neurons in macaque monkeys performing a reaction-time detection task. We find that most V1 neurons gradually depolarize in preparation for target onset. Remarkably, trial-to-trial variations in this preparatory buildup are correlated with the monkey’s reaction times, and these covariations are similar when the animal selects a target in either hemifield. This finding implies that variation in the preparatory buildup are shared between hemispheres and are unrelated to a competitive spatial attention mechanism. Further, we find that while the gradual buildup is largely uncorrelated with the animals’ choices, transient fluctuations in Vm around target-evoked response onset time are correlated with choice. The dependence of these Vm-to-choice covariations on the visual stimulus is consistent with a multiplicative gain, reflecting a variable internal state that interacts with variable sensory signals. Overall, our results reveal surprising covariations between the membrane potential of single V1 neurons and behavior, and that these covariations are mediated by mixture of additive and multiplicative task-related modulations of incoming sensory information.

Animals use a combination of eye movements to track moving objects. These different eye movements need to be coordinated for successful tracking, requiring interactions between the systems involved. Here, we study the interaction between the saccadic and smooth pursuit eye movement systems in marmosets. Using a single-target pursuit task, we show that saccades cause an enhancement in pursuit following a saccade. Using a two-target pursuit task, we show that this enhancement in pursuit is selective toward the motion of the target selected by the saccade, irrespective of any biases in pursuit prior to the saccade. These experiments highlight the similarities in the functioning of saccadic and smooth pursuit eye movement systems across primates.