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.

Regional and cell-type-specific afferent and efferent projections of the mouse claustrum.

The claustrum (CLA) is a conspicuous subcortical structure interconnected with cortical and subcortical regions. Its regional anatomy and cell-type-specific connections in the mouse remain not fully determined. Using multimodal reference datasets, we confirmed the delineation of the mouse CLA as a single group of neurons embedded in the agranular insular cortex. We quantitatively investigated brain-wide inputs and outputs of CLA using bulk anterograde and retrograde viral tracing data and single neuron tracing data. We found that the prefrontal module has more cell types projecting to the CLA than other cortical modules, with layer 5 IT neurons predominating. We found nine morphological types of CLA principal neurons that topographically innervate functionally linked cortical targets, preferentially the midline cortical areas, secondary motor area, and entorhinal area. Together, this study provides a detailed wiring diagram of the cell-type-specific connections of the mouse CLA, laying a foundation for studying its functions at the cellular level.

Use of mental health services by children and youth in Ontario military families compared with the general population: a retrospective cohort study.

BACKGROUND: In Canada, more than 64 000 children are growing up with 1 or both parents in the military. We compared mental health service use by children and youth in military families versus the general population, to understand potential mental health service gaps. METHODS: This was a matched retrospective cohort study of children and youth (aged < 20 yr) of members of the Canadian Armed Forces posted to Ontario between Apr. 1, 2008, and Mar. 31, 2013, with follow-up to Mar. 31, 2017, using provincial administrative health data at ICES. We created a comparison group of children and youth in the general population, matched 4:1 by age, sex and geography. We compared the use and frequency of mental health-related physician visits, emergency department visits and hospital admissions, and the time to first service use, using regression models. RESULTS: This study included 5478 children and youth in military families and a matched cohort of 21 912 children and youth in the general population. For visits and admissions for mental health reasons, children and youth in military families were more likely to see a family physician (adjusted relative risk [RR] 1.25, 95% confidence interval [CI] 1.17 to 1.34), less likely to see a pediatrician (adjusted RR 0.87, 95% CI 0.79 to 0.96), equally likely to see a psychiatrist, and as likely to visit an emergency department or be admitted to hospital as the matched cohort. Children and youth in military families had the same frequency of use of outpatient mental health services. The time to first visit for mental health reasons was shorter to see a family physician (adjusted days difference [DD] -57, 95% CI -80 to -33) and longer to see a psychiatrist (adjusted DD 103, 95% CI 43 to 163) for children and youth in military families. INTERPRETATION: Children and youth in military families use mental health services differently from those in the general population. Provincial policies aimed at increasing access to mental health specialists for children and youth in military families, alongside targeted federal services and programming through military organizations, are needed.

RecV recombinase system for in vivo targeted optogenomic modifications of single cells or cell populations.

Brain circuits comprise vast numbers of interconnected neurons with diverse molecular, anatomical and physiological properties. To allow targeting of individual neurons for structural and functional studies, we created light-inducible site-specific DNA recombinases based on Cre, Dre and Flp (RecVs). RecVs can induce genomic modifications by one-photon or two-photon light induction in vivo. They can produce targeted, sparse and strong labeling of individual neurons by modifying multiple loci within mouse and zebrafish genomes. In combination with other genetic strategies, they allow intersectional targeting of different neuronal classes. In the mouse cortex they enable sparse labeling and whole-brain morphological reconstructions of individual neurons. Furthermore, these enzymes allow single-cell two-photon targeted genetic modifications and can be used in combination with functional optical indicators with minimal interference. In summary, RecVs enable spatiotemporally precise optogenomic modifications that can facilitate detailed single-cell analysis of neural circuits by linking genetic identity, morphology, connectivity and function.