Identification of a Brainstem Circuit Regulating Visual Cortical State in Parallel with Locomotion

SummarySensory processing is dependent upon behavioral state. In mice, locomotion is accompanied by changes in cortical state and enhanced visual responses. Although recent studies have begun to elucidate intrinsic cortical mechanisms underlying this effect, the neural circuits that initially couple locomotion to cortical processing are unknown. The mesencephalic locomotor region (MLR) has been shown to be capable of initiating running and is associated with the ascending reticular activating system. Here, we find that optogenetic stimulation of the MLR in awake, head-fixed mice can induce both locomotion and increases in the gain of cortical responses. MLR stimulation below the threshold for overt movement similarly changed cortical processing, revealing that MLR’s effects on cortex are dissociable from locomotion. Likewise, stimulation of MLR projections to the basal forebrain also enhanced cortical responses, suggesting a pathway linking the MLR to cortex. These studies demonstrate that the MLR regulates cortical state in parallel with locomotion

How Cortical Circuits Implement Cortical Computations: Mouse Visual Cortex as a Model

The mouse, as a model organism to study the brain, gives us unprecedented experimental access to the mammalian cerebral cortex. By determining the cortex's cellular composition, revealing the interaction between its different components, and systematically perturbing these components, we are obtaining mechanistic insight into some of the most basic properties of cortical function. In this review, we describe recent advances in our understanding of how circuits of cortical neurons implement computations, as revealed by the study of mouse primary visual cortex. Further, we discuss how studying the mouse has broadened our understanding of the range of computations performed by visual cortex. Finally, we address how future approaches will fulfill the promise of the mouse in elucidating fundamental operations of cortex

Illuminating the Neural Circuits Underlying Orienting of Attention

Human neuroimaging has revealed brain networks involving frontal and parietal cortical areas as well as subcortical areas, including the superior colliculus and pulvinar, which are involved in orienting to sensory stimuli. Because accumulating evidence points to similarities between both overt and covert orienting in humans and other animals, we propose that it is now feasible, using animal models, to move beyond these large-scale networks to address the local networks and cell types that mediate orienting of attention. In this opinion piece, we discuss optogenetic and related methods for testing the pathways involved, and obstacles to carrying out such tests in rodent and monkey populations

Functional imaging reveals rapid development of visual response properties in the zebrafish tectum

ment. While a number of studies have addressed th

Multimodal Deep Learning Model Unveils Behavioral Dynamics of V1 Activity in Freely Moving Mice

Code is at https://github.com/bionicvisionlab/2023-Xu-Multimodal-Mouse-V

TU-tagging: A method for identifying layer-enriched neuronal genes in developing mouse visual cortex

Thiouracil (TU)-tagging is an intersectional method for covalently labeling newly transcribed RNAs within specific cell types. Cell type specificity is generated through targeted transgenic expression of the enzyme uracil phosphoribosyl transferase (UPRT); temporal specificity is generated through a pulse of the modified uracil analog 4TU. This technique has been applied in mouse using a Cre-dependent UPRT transgene, CA>GFPstop>HA-UPRT, to profile RNAs in endothelial cells, but it remained untested whether 4TU can cross the blood-brain barrier (BBB) or whether this transgene can be used to purify neuronal RNAs. Here, we crossed the CA>GFPstop>HA-UPRT transgenic mouse to a Sepw1-cre line to express UPRT in layer 2/3 of visual cortex or to an Nr5a1-cre line to express UPRT in layer 4 of visual cortex. We purified thiol-tagged mRNA from both genotypes at postnatal day (P)12, as well as from wild-type (WT) mice not expressing UPRT (background control). We found that a comparison of Sepw1-purified RNA to WT or Nr5a1-purified RNA allowed us to identify genes enriched in layer 2/3 of visual cortex. Here, we show that Cre-dependent UPRT expression can be used to purify cell type-specific mRNA from the intact mouse brain and provide the first evidence that 4TU can cross the BBB to label RNA in vivo