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.

Summary 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-expressing (SOM) interneurons show histological abnormalities in individuals with schizophrenia, and they 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 hippocampalprefrontal 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.

Highlights d Oscillatory, not pulsatile, stimulation of vHPC-mPFC at 8 Hz increased avoidance d Oscillatory stimulation of vHPC-mPFC at 2 or 20 Hz did not increase avoidance d Oscillatory stimulation of vHPC-mPFC facilitated neural transmission in this pathway d 8-Hz oscillatory stimulation increased vHPC-mPFC theta synchrony during the EPM

Saccades are a ubiquitous and crucial component of our visual system, allowing for the efficient deployment of the fovea and its accompanying neural resources. Initiation of a saccade is known to cause saccadic suppression, a temporary reduction in visual sensitivity1,2 and visual cortical firing rates3–6. 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 area V4. We find cortical layer- and cell type-specific differences in the magnitude and timing of peri-saccadic modulation. Neurons in the input layer show changes in firing rate and inter-neuronal correlations prior to saccade onset, suggesting that this layer receives information about impending saccades. Putative inhibitory interneurons in the input layer elevate their firing rate during saccades and may suppress the activity of other cortical subpopulations. 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. Together, our results provide a mechanistic understanding of how eye movement signaling interacts with cortical circuitry to enforce visual stability.