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Cang, J.

Publications and source records attributed to Cang, J..

7 recordsLinked to original sources

Distinct processing of visual motion by transcriptomic cell types in the superior colliculus

How the brain organizes visual processing across distinct neuron types is a fundamental yet unresolved question. Here we study how visual motion is processed by transcriptomically defined cell types in the superior colliculus (SC). We generated or identified transgenic mouse lines to target three transcriptomic types of neurons in the superficial SC, the Cbln4+, Vip+, and Grp+ neurons. We find that each of these cell types encodes distinct ranges of stimulus direction, speed, size, and spatial and temporal features. In response to ecologically relevant visual flows, the three cell types occupy partitional spaces in the encoding manifold. The three cell types also show unique morphology and connectivity, including their retinal and intracollicular input and projection patterns. Together, these results reveal a genetic logic for visual motion processing in the SC, where transcriptomic cell types are likely the basic computational units with their specific feature selectivity, morphology, and input-output connectivity.

neuroscience↗

A geniculocortical circuit model predicts functional organization underlying efficient spatial frequency coding in the mouse visual system

Neural encoding of sensory information becomes more efficient when distinct stimuli evoke uncorrelated activity patterns. Spatial frequency (SF) information becomes decorrelated early in visual processing in a manner that involves both temporal differentiation in the dorsal lateral geniculate nucleus (dLGN) and firing rate differentiation in the primary visual cortex (V1). However, the specific functional circuit configurations that enable this synergy are not fully understood. To address this gap, we developed a geniculocortical subunit model to identify functional circuit configurations capable of producing a decorrelated V1 population response. We found that decorrelation could be explained by the combined activity of two complementary circuit configurations with distinct functional organization. The first circuit was characterized by temporally organized, late-onset dLGN inputs coupled to weak and delayed intracortical inhibition, whereas the second was characterized by less temporally constrained, early-onset dLGN inputs coupled to strong and early intracortical inhibition. Eliminating SF selectivity in upstream dLGN subunits did not affect SF decorrelation in the modeled V1 population response, indicating that decorrelation tolerates weak SF selectivity and is primarily driven by temporal organization. Together, these results suggest that biologically plausible circuit configurations are likely to produce SF decorrelation in the cortex through the temporal organization of feedforward inputs and intracortical inhibition.

neuroscience↗

Co-Conservation of Synaptic Gene Expression and Circuitry in Collicular Neurons

The superior colliculus (SC), a midbrain sensorimotor hub, is anatomically and functionally similar across vertebrates, but how its cell types have evolved is unclear. Using single-nucleus transcriptomics, we compared the SCs molecular and cellular organization in mice, tree shrews, and humans. Despite over 96 million years of evolutionary divergence, we identified [~]30 consensus neuronal subtypes, including Cbln2+ neurons that form the SC-pulvinar circuit in mice and tree shrews. Synapse-related genes were among the most conserved, unlike neocortex, suggesting co-conservation of synaptic genes and circuitry. In contrast, cilia-related genes diverged significantly across species, highlighting the potential importance of the neuronal primary cilium in SC evolution. Additionally, we identified a novel inhibitory SC neuron in tree shrews and humans but not mice. Our findings reveal that the SC has evolved by conserving neuron subtypes, synaptic genes, and circuitry, while diversifying ciliary gene expression and an inhibitory neuron subtype.

neuroscience↗

Cerebral Blood Volume Modulates Glymphatic Influx Through Extra-ventricular Cerebrospinal Fluid Volume

The glymphatic system facilitates waste removal via cerebrospinal fluid (CSF) influx alongside perivascular spaces throughout the brain. Vasomotion, the slow motion of blood vessel (0.1-0.3 Hz), has been found to be one of the driving forces for perivascular clearance, but it is not clear whether more chronical change of vessel diameter, as reflected by macroscopic cerebral blood volume (CBV), has any impact on glymphatic function. Combining multimodal mouse MRI techniques, we investigated the relationship among glymphatic influx, CBV, CSF volume and EEG power under six different conditions (awake, dexmedetomidine, isoflurane, isoflurane/dexmedetomidine, ketamine/xylazine and awake with caffeine). We found dexmedetomidine and caffeine enhanced glymphatic influx, while isoflurane reduced it compared with awake condition. Quantitative CBV imaging revealed that glymphatic influx was negatively correlated to CBV across the above conditions. Furthermore, such negative correlation was found to be mediated in part by changes of extra-ventricular CSF volume, which was quantified using T1 MRI. Taken together, our results suggest that CBV is a consciousness independent modulator of glymphatic function and modulates glymphatic influx through extra-ventricular CSF volume. This new finding opens potential avenues to enhance brain waste clearance by regulating CBV, which could be beneficial for protein deposition related neurological diseases. TeaserCBV is a consciousness independent modulator of glymphatic function and modulates glymphatic influx through extra-ventricular CSF volume.

neuroscience↗

Global Mapping of Mouse CSF Flow via HEAP-METRIC Phase-contrast MRI

Roles of Cerebrospinal fluid (CSF) in brain waste clearance and homeostasis has been increasingly recognized, thus measuring its flow dynamics could provide important information about its function and perturbance. While phase-contrast MRI can be used for non-invasive flow mapping, so far its mapping of low velocity flow (such as mouse brain CSF) is not possible. Here we developed a novel generalized Hadamard encoding based multi-band acceleration scheme dubbed HEAP-METRIC (Hadamard Encoding APproach of Multi-band Excitation for short TR Imaging aCcelerating), and with significantly increased SNR per time, HEAP-METRIC phase-contrast MRI achieved fast and accurate mapping of slow (~102 micron/s) flow. Utilizing this novel method, we revealed a heterogeneous global pattern of CSF flow in the awake mouse brain with a averaged flow of ~200 micron/s, and further found isoflurane anesthesia reduced CSF flow that was accompanied by reduction of glymphatic function. Therefore, we developed the novel HEAP-METRIC phase-contrast MRI for mapping low velocity flow, and demonstrated its capability for global mapping of mouse CSF flow and its potential alterations related to various physiological or pathological conditions.

neuroscience↗

MECP2 duplication causes aberrant GABA pathways, circuits and behaviors in transgenic monkeys: neural mappings to patients with autism

MECP2 gain- and loss-of-function in genetically-engineered monkeys demonstrably recapitulate typical phenotypes in patients, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remains unknown. Using expression profiles of 13,888 genes in 182 macaque neocortical samples, we first show that MECP2 coexpressed genes are enriched in GABA-related signaling pathways. We then perform analyses on multiple phenotypic levels including locomotive and cognitive behavior, resting-state electroencephalography and fMRI in MECP2 overexpressed and wild-type macaque monkeys. Behaviorally, transgenic monkeys exhibit hyperactive and repetitive locomotion, greater separation anxiety response, and less flexibility in rule switching. Moreover, decreased neural synchronization at beta frequency (12-30 Hz) is associated with greater locomotion after peer separation. Further analysis of fMRI-derived connectomics reveals widespread hyper- and hypo-connectivity, where hyper-connectivity prominently involving prefrontal and cingulate networks accounts for deficits in cognitive flexibility. To map MECP2-related aberrant circuits of monkeys to the pathological circuits of autistic patients, individuals in a large public neuroimaging database of autism were clustered using community detection on functional connectivity patterns. In a stratified cohort of 49 autisms and 72 controls, the dysfunctional connectivity profile particularly in prefrontal and temporal networks is highly correlated with that of transgenic monkeys, as is further responsible for the severity of social communicative deficits in patients. Through establishing a circuit-based construct link between transgenic animal models and stratified clinical patients, the present findings with explicable biological causes are potentially amenable to translation for accurate diagnosis and evaluation of future treatments in autism-related disorders.\n\nOne sentence summaryWe identify shared circuit-level abnormalities between MECP2 transgenic monkeys and a stratified subgroup of human autism, and demonstrate the translational need of a multimodal approach to capture multifaceted effects triggered by a single genetic event in a genetically-engineered primate model.

neuroscience↗

Development and Binocular Matching of Orientation Selectivity in Visual Cortex: A Computational Model

In mouse visual cortex, right after eye-opening binocular cells have different orientation preferences for input from the two eyes. With normal visual experience during a critical period, these orientation preferences shift and eventually become well matched. To gain insight into the matching process, we developed a computational model of a cortical cell receiving - via plastic synapses - orientation selective inputs that are individually monocular. The model captures the experimentally observed matching of the orientation preferences, the dependence of matching on ocular dominance of the cell, and the relationship between the degree of matching and the resulting monocular orientation selectivity. Moreover, our model puts forward testable predictions: i) the matching speed increases with initial ocular dominance and decreases with initial orientation selectivity; ii) matching proceeds faster than the sharpening of the orientation selectivity, suggesting that orientation selectivity is not a driving force for the matching process; iii) there are two main routes to matching: the preferred orientations either drift towards each other or one of the orientations switches suddenly. The latter occurs for cells with large initial mismatch and can render the cell monocular. We expect that these results provide insight more generally into the development of neuronal systems that integrate inputs from multiple sources, including different sensory modalities.\n\nNew & NoteworthyAnimals gather information through multiple modalities (vision, audition, touch, etc). These information streams have to be merged coherently to provide a meaningful representation of the world. Thus, for neurons in visual cortex V1 the orientation selectivities for inputs from the two eyes have to match to enable binocular vision. We analyze the postnatal process underlying this matching using computational modeling. It captures recent experimental results and reveals interdependence between matching, ocular dominance, and orientation selectivity.

neuroscience↗