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Peterson, Z. J.

Publications and source records attributed to Peterson, Z. J..

3 recordsLinked to original sources

The transcriptomic architecture of the human cerebral cortex

For over a century, scientists have been attempting to map the human cerebral cortex, however, they have not taken into account the complex molecular structure of the cortex, which is only beginning to be understood. Here, we parcellate the human cerebral cortex using a machine learning (ML) approach to define its transcriptomic architecture, revealing a multi-resolution organization across individuals. The transcriptomically-derived spatial patterns of gene expression separate the cortex into three major regions, frontal, temporal and parietooccipital, with smaller subregions appearing at lower levels of the transcriptomic hierarchy. The core regions, which remain stable across different hierarchical levels, are physiologically associated with language, emotion regulation, social cognition, motor and visuospatial processing and planning. Importantly, some core regions cross structural and anatomical boundaries identified in previous parcellations of the cortex, revealing that the transcriptomic architecture of the cortex is closely linked to human-specific higher cognitive function.

neuroscience↗

Lateral Septal Circuits Govern Schizophrenic-Like Effects of Ketamine on Social Behavior

Schizophrenia is marked by poor social functioning that can have a severe impact on quality of life and independence, but the underlying neural circuity is not well understood. Here we used a translational model of subanesthetic ketamine in mice to delineate neural pathways in the brain linked to social deficits in schizophrenia. Mice treated with chronic ketamine (30 mg/kg/day for 10 days) exhibit profound social and sensorimotor deficits as previously reported. Using three- dimensional c-Fos immunolabeling and volume imaging (iDISCO), we show that ketamine treatment resulted in hypoactivation of the lateral septum (LS) in response to social stimuli. Chemogenetic activation of the LS rescued social deficits after ketamine treatment, while chemogenetic inhibition of previously active populations in the LS (i.e. social engram neurons) recapitulated social deficits in ketamine-naive mice. We then examined the translatome of LS social engram neurons and found that ketamine treatment dysregulated genes implicated in neuronal excitability and apoptosis, which may contribute to LS hypoactivation. We also identified 38 differentially expressed genes (DEGs) in common with human schizophrenia, including those involved in mitochondrial function, apoptosis, and neuroinflammatory pathways. Chemogenetic activation of LS social engram neurons induced downstream activity in the ventral part of the basolateral amygdala, subparafascicular nucleus of the thalamus, intercalated amygdalar nucleus, olfactory areas, and dentate gyrus, and it also reduces connectivity of the LS with the piriform cortex and caudate-putamen. In sum, schizophrenia-like social deficits may emerge via changes in the intrinsic excitability of a discrete subpopulation of LS neurons that serve as a central hub to coordinate social behavior via downstream projections to reward, fear extinction, motor and sensory processing regions of the brain.

neuroscience↗

Acid enhances salt taste by activating the epithelial sodium channel

Salt is often used to enhance the flavor of foods and drinks, and in turn, some foods and drinks may intensify the taste of salt. For example, highly acidic carbonated beverages sometimes accompany salty snacks, and margaritas made with acidic citrus are served in salt-rimmed glasses. However, whether and how acid might enhance salt taste remain unknown. Epithelial sodium channels (ENaC) in tongue taste cells detect dietary sodium. We found that acid irreversibly increased ENaC channel activity, with half-maximal activation occurring at pH 2.6. Acid altered ENaC gating by increasing the rate of channel opening and reducing the rate of channel closing. Acidic beverages Coca-Cola(R) and Pepsi(R) (pH 2.2-2.4) also stimulated ENaC current but Diet Coke(R) (pH 3.2) did not. In humans, we found that acid reduced the sodium taste detection threshold. These findings identify a functional interplay between dietary sodium and acid--by modulating ENaC gating, acid enhances salt taste.

physiology↗