Coordinated changes in a cortical circuit sculpt effects of novelty on neural dynamics.

Recent studies have found dramatic cell-type specific responses to stimulus novelty, highlighting the importance of analyzing the cortical circuitry at the cell-type specific level of granularity to understand brain function. Although initial work classified and characterized activity for each cell type, the specific alterations in cortical circuitry-particularly when multiple novelty effects interact-remain unclear. To address this gap, we employed a large-scale public dataset of electrophysiological recordings in the visual cortex of awake, behaving mice using Neuropixels probes and designed population network models to investigate the observed changes in neural dynamics in response to a combination of distinct forms of novelty. The model parameters were rigorously constrained by publicly available structural datasets, including multi-patch synaptic physiology and electron microscopy data. Our systematic optimization approach identified tens of thousands of model parameter sets that replicate the observed neural activity. Analysis of these solutions revealed generally weaker connections under novel stimuli, as well as a shift in the balance e between SST and VIP populations. Along with this, PV and SST populations experienced overall more excitatory influences compared to excitatory and VIP populations. Our results also highlight the role of VIP neurons in multiple aspects of visual stimulus processing and altering gain and saturation dynamics under novel conditions. In sum, our findings provide a systematic characterization of how the cortical circuit adapts to stimulus novelty by combining multiple rich public datasets.

Recurrent pattern completion drives the neocortical representation of sensory inference.

When sensory information is incomplete or ambiguous, the brain relies on prior expectations to infer perceptual objects. Despite the centrality of this process to perception, the neural mechanism of sensory inference is not known. Illusory contours (ICs) are key tools to study sensory inference because they contain edges or objects that are implied only by their spatial context. Using cellular resolution, mesoscale two-photon calcium imaging and multi-Neuropixels recordings in the mouse visual cortex, we identified a sparse subset of neurons in the primary visual cortex (V1) and higher visual areas that respond emergently to ICs. We found that these highly selective 'IC-encoders' mediate the neural representation of IC inference. Strikingly, selective activation of these neurons using two-photon holographic optogenetics was sufficient to recreate IC representation in the rest of the V1 network, in the absence of any visual stimulus. This outlines a model in which primary sensory cortex facilitates sensory inference by selectively strengthening input patterns that match prior expectations through local, recurrent circuitry. Our data thus suggest a clear computational purpose for recurrence in the generation of holistic percepts under sensory ambiguity. More generally, selective reinforcement of top-down predictions by pattern-completing recurrent circuits in lower sensory cortices may constitute a key step in sensory inference.

Refractory and Super-Refractory Status Epilepticus in Nerve Agent-Poisoned Rats Following Application of Standard Clinical Treatment Guidelines.

Nerve agents (NAs) induce a severe cholinergic crisis that can lead to status epilepticus (SE). Current guidelines for treatment of NA-induced SE only include prehospital benzodiazepines, which may not fully resolve this life-threatening condition. This study examined the efficacy of general clinical protocols for treatment of SE in the specific context of NA poisoning in adult male rats. Treatment with both intramuscular and intravenous benzodiazepines was entirely insufficient to control SE. Second line intervention with valproate (VPA) initially terminated SE in 35% of rats, but seizures always returned. Phenobarbital (PHB) was more effective, with SE terminating in 56% of rats and 19% of rats remaining seizure-free for at least 24 h. The majority of rats demonstrated refractory SE (RSE) and required treatment with a continuous third-line anesthetic. Both ketamine (KET) and propofol (PRO) led to high levels of mortality, and nearly all rats on these therapies had breakthrough seizure activity, demonstrating super-refractory SE (SRSE). For the small subset of rats in which SE was fully resolved, significant improvements over controls were observed in recovery metrics, behavioral assays, and brain pathology. Together these data suggest that NA-induced SE is particularly severe, but aggressive treatment in the intensive care setting can lead to positive functional outcomes for casualties.