Reverse-translational identification of a cerebellar satiation network

Low, Aloysius Y. T.; Goldstein, Nitsan; Gaunt, Jessica; Huang, Kuei-Pin; Zainolabidin, Norliyana; Yip, Alaric K. K.; Carty, Jamie R. E.; Choi, Ju Y.; Miller, Alekso M.; Ho, Helen Shen Ting; Lenherr, Clara; Baltar, Nicholas; Azim, Eiman; Sessions, October M.; Ch’ng, Toh Hean; Bruce, Amanda S.; Martin, Laura E.; Halko, Mark A.; Brady, Roscoe O.; Holsen, Laura M.; Alhadeff, Amber L.; Chen, Albert I.; Betley, J. Nicholas

doi:10.1038/s41586-021-04143-5

Cited by 83 publications

(73 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This circuit may be conserved: Eurydendroid cells are considered homologous to the deep cerebellar nuclei in mammals (Bae et al, 2009; Heap et al, 2013). In humans and mice, deep cerebellar nuclei are activated after ingestion of food and may signal satiety (Low et al, 2021). While an experimental test of this hypothesis is beyond the scope of the current work, the newly discovered correspondence illustrates the power of integrating gene expression, functional cfos labeling, transgene and single-cell reconstructions in a multimodal atlas resource.…”

Section: Resultsmentioning

confidence: 99%

A single-cell resolution gene expression atlas of the larval zebrafish brain

Shainer

Kuehn

Laurell

et al. 2022

Preprint

View full text Add to dashboard Cite

The advent of multimodal brain atlases promises to accelerate discoveries in neuroscience by offering in silico queries of cell types, connectivity and gene expression in regions of interest. We employed multiplexed fluorescent in situ RNA hybridization chain reaction (HCR) to generate expression maps for an initial set of 200 marker genes across the larval zebrafish brain. The data were registered to the Max Planck Zebrafish Brain (mapzebrain) atlas, thus allowing co-visualization of gene expression patterns, single-neuron tracings, transgenic lines and anatomical segmentations. Additionally, brain activity maps of freely swimming larvae were generated at single-cell resolution using HCR labeling of the immediate-early gene cfos and integrated into the atlas. As a proof of concept, we identified a novel class of cerebellar eurydendroid cells that express calb2a, project to the hypothalamus and are activated in animals that have recently ingested food. Thus, a cellular-resolution gene expression atlas will not only help with rapid identification of marker genes for neuronal populations of interest, but also bridge the molecular and circuit levels by anchoring genetic information to functional activity maps and synaptic connectivity.

show abstract

Section: Resultsmentioning

confidence: 99%

A single-cell resolution gene expression atlas of the larval zebrafish brain

Shainer

Kuehn

Laurell

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…There is also emerging evidence for cerebellar involvement in food intake. Human neuroimaging studies have reported cerebellar responses to food-related stimuli (Huerta et al, 2014) that are blunted by satiation (Tataranni et al, 1999; Small et al, 2001) and in hyperphagic individuals with Prader-Willi syndrome (Blanco-Hinojo et al, 2019; Low et al, 2021). There is also a population of neurons in the deep cerebellar nuclei that are proposed to act as a satiation network by modulating the dopaminergic system toward reducing food intake in mice (Low et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Olfactory decoding is positively associated with ad libitum food intake in sated humans

Perszyk

Davis

2022

Preprint

View full text Add to dashboard Cite

The role of olfaction in eating behavior and body weight regulation is controversial. Here we used functional magnetic resonance imaging to test whether central olfactory coding is associated with internal state, food intake, and change in body weight over one year in healthy human adults. Since odor quality and category are coded across distributed neural patterns that are not discernible with traditional univariate analyses, we used multi-voxel pattern analyses to decode patterns of brain activation to food versus nonfood odors. We found that decoding accuracies in the piriform cortex and amygdala were greater in the sated compared to hungry state. Sated decoding accuracies in these and other regions were also associated with post-scan ad libitum food intake, but not with weight change. These findings demonstrate that the fidelity of olfactory decoding is influenced by internal state and is associated with immediate food intake, but not longer-term body weight regulation.

show abstract

“…Moreover, we observed neurons expressing tdTomato sparsely distributed in the dorsomedial and lateral hypothalamus. The cerebellarhypothalamic contacts may be important for somatic and visceral integration [69][70][71] . Among the secondorder nuclei, robust axon (not soma) labeling was apparent in subcortical regions, e.g., the dorsal striatum (dSTR) and nucleus accumbens (NAc) (Fig.…”

Section: Anatomical Tracing Of the Medial Cerebellar Nucleo-cortical ...mentioning

confidence: 99%

Social memory deficit gated by dysregulation of the cerebellar vermis

Chao

Pathak

Zhang

et al. 2022

Preprint

View full text Add to dashboard Cite

Social recognition memory (SRM) is a key determinant of social behavior because it integrates past experiences into social interactions to distinguish familiar from novel conspecifics. The cerebellum is an important region for social functions; dysregulated cerebellar output is a common phenotype in various mouse models of autism. However, how the abnormal local activity in the cerebellum leads to social behavior deficits remains unknown. To this end, we selectively increased the excitability of molecular layer interneurons (MLIs) to suppress Purkinje cell (PC) firing with chemo- and optogenetic approaches in the mouse cerebellar vermis. Chemogenetic perturbation of MLIs impaired SRM without affecting sociability, anxiety levels, motor coordination or object recognition. Optogenetic interference of MLIs during distinct phases of a social recognition test highlighted cerebellar engagement in retrieval, but not encoding, of social information. Functional mapping with an immediate early gene product (c-Fos) following the social recognition test revealed that cerebellar manipulation significantly reduced brain-wide interregional correlations and shifted network structure from the medial prefrontal cortex (mPFC) and hippocampus- to amygdala-centered modules. Transsynaptic tracing showed hierarchical projections from the central cerebellum to the social brain network. Collectively, our results suggest that the cerebellum organizes the neural matrix required for SRM, providing a circuitry basis for social impairments in autism and other psychiatric disorders.

show abstract

Reverse-translational identification of a cerebellar satiation network

Cited by 83 publications

References 84 publications

A single-cell resolution gene expression atlas of the larval zebrafish brain

A single-cell resolution gene expression atlas of the larval zebrafish brain

Olfactory decoding is positively associated with ad libitum food intake in sated humans

Social memory deficit gated by dysregulation of the cerebellar vermis

Contact Info

Product

Resources

About