Non-uniform contextual interactions in the visual cortex place fundamental limits on spatial vision.

A prevailing assumption in our understanding of how neurons in the primary visual cortex (V1) integrate contextual information is that such processes are spatially uniform. Conversely, perceptual phenomena such as visual crowding, the impaired ability to accurately recognize a target stimulus among distractors, suggest that interactions among stimuli are distinctly non-uniform. Prior studies have shown flankers at specific spatial geometries exert differential effects on target perception. To resolve this discrepancy, we investigated how flanker geometry impacted the representation of a target stimulus in the laminar microcircuits of V1. Our study reveals flanker location differentially impairs stimulus representation in excitatory neurons in the superficial and input layers of V1 by tuned suppression and untuned facilitation of orientation responses. Mechanistically, this effect can be explained by asymmetrical spatial kernels in a normalization model of cortical activity. Strikingly, these non-uniform modulations of neural representation mirror perceptual anisotropies. These results establish the non-uniform spatial integration of information in the earliest stages of cortical processing as a fundamental limitation of spatial vision.

WIDESPREAD RECEPTIVE FIELD REMAPPING IN EARLY VISUAL CORTEX.

Our eyes are in constant motion, yet we perceive the visual world as being stable. Predictive remapping of receptive fields is thought to be one of the critical mechanisms for enforcing perceptual stability during eye movements. While receptive field remapping has been identified in several cortical areas, the spatiotemporal dynamics of remapping, and its consequences on the tuning properties of neurons, remain poorly understood. Here, we tracked remapping receptive fields in hundreds of neurons from visual Area V2 while subjects performed a cued saccade task. We found that remapping was far more widespread in Area V2 than previously reported and can be found in neurons from all recorded neural populations in the laminar cortical circuit. Surprisingly, neurons undergoing remapping exhibit sensitivity to two punctate locations in visual space. Remapping is also accompanied by a transient sharpening of orientation tuning. Taken together, these results shed light on the spatiotemporal dynamics of remapping and its ubiquitous prevalence in the early visual cortex, and force us to revise current models of perceptual stability.

Laminar mechanisms of saccadic suppression in primate visual cortex.

Saccadic eye movements are known to cause saccadic suppression, a temporary reduction in visual sensitivity and visual cortical firing rates. While saccadic suppression has been well characterized at the level of perception and single neurons, relatively little is known about the visual cortical networks governing this phenomenon. Here we examine the effects of saccadic suppression on distinct neural subpopulations within visual area V4. We find subpopulation-specific differences in the magnitude and timing of peri-saccadic modulation. Input-layer neurons show changes in firing rate and inter-neuronal correlations prior to saccade onset, and putative inhibitory interneurons in the input layer elevate their firing rate during saccades. A computational model of this circuit recapitulates our empirical observations and demonstrates that an input-layer-targeting pathway can initiate saccadic suppression by enhancing local inhibitory activity. Collectively, our results provide a mechanistic understanding of how eye movement signaling interacts with cortical circuitry to enforce visual stability.

Hippocampal-Prefrontal Theta Transmission Regulates Avoidance Behavior.

Long-range synchronization of neural oscillations correlates with distinct behaviors, yet its causal role remains unproven. In mice, tests of avoidance behavior evoke increases in theta-frequency (∼8 Hz) oscillatory synchrony between the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC). To test the causal role of this synchrony, we dynamically modulated vHPC-mPFC terminal activity using optogenetic stimulation. Oscillatory stimulation at 8 Hz maximally increased avoidance behavior compared to 2, 4, and 20 Hz. Moreover, avoidance behavior was selectively increased when 8-Hz stimulation was delivered in an oscillatory, but not pulsatile, manner. Furthermore, 8-Hz oscillatory stimulation enhanced vHPC-mPFC neurotransmission and entrained neural activity in the vHPC-mPFC network, resulting in increased synchrony between vHPC theta activity and mPFC spiking. These data suggest a privileged role for vHPC-mPFC theta-frequency communication in generating avoidance behavior and provide direct evidence that synchronized oscillations play a role in facilitating neural transmission and behavior.

Somatostatin Interneurons Facilitate Hippocampal-Prefrontal Synchrony and Prefrontal Spatial Encoding.

Decreased hippocampal-prefrontal synchrony may mediate cognitive deficits in schizophrenia, but it remains unclear which cells orchestrate this long-range synchrony. Parvalbumin (PV)- and somatostatin (SOM)-expressing interneurons show histological abnormalities in individuals with schizophrenia and are hypothesized to regulate oscillatory synchrony within the prefrontal cortex. To examine the relationship between interneuron function, long-range hippocampal-prefrontal synchrony, and cognition, we optogenetically inhibited SOM and PV neurons in the medial prefrontal cortex (mPFC) of mice performing a spatial working memory task while simultaneously recording neural activity in the mPFC and the hippocampus (HPC). We found that inhibiting SOM, but not PV, interneurons during the encoding phase of the task impaired working memory accuracy. This behavioral impairment was associated with decreased hippocampal-prefrontal synchrony and impaired spatial encoding in mPFC neurons. These findings suggest that interneuron dysfunction may contribute to cognitive deficits associated with schizophrenia by disrupting long-range synchrony between the HPC and PFC.

A Novel Method for Chronic Social Defeat Stress in Female Mice.

Historically, preclinical stress studies have often omitted female subjects, despite evidence that women have higher rates of anxiety and depression. In rodents, many stress susceptibility and resilience studies have focused on males as one commonly used paradigm-chronic social defeat stress-has proven challenging to implement in females. We report a new version of the social defeat paradigm that works in female mice. By applying male odorants to females to increase resident male aggressive behavior, we find that female mice undergo repeated social defeat stress and develop social avoidance, decreased sucrose preference, and decreased time in the open arms of the elevated plus maze relative to control mice. Moreover, a subset of the female mice in this paradigm display resilience, maintaining control levels of social exploration and sucrose preference. This method produces comparable results to those obtained in male mice and will greatly facilitate studying female stress susceptibility.