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• W2512338506 abstract "Glutamate neurotransmission refines synaptic connections to establish the precise neural circuits underlying sensory processing. Deleting metabotropic glutamate receptor 5 (mGluR5) in mice perturbs cortical somatosensory map formation in the primary somatosensory (S1) cortex at both functional and anatomical levels. To examine the cell-autonomous influences of mGluR5 signaling in the morphological and functional development of layer IV spiny stellate glutamatergic neurons receiving sensory input, mGluR5 genetic mosaic mice were generated through <i>in utero</i> electroporation. In the S1 cortex of these mosaic brains, we found that most wild-type neurons were located in barrel rings encircling thalamocortical axon (TCA) clusters while mGluR5 knock-out (KO) neurons were placed in the septal area, the cell-sparse region separating barrels. These KO neurons often displayed a symmetrical dendritic morphology with increased dendritic complexity, in contrast to the polarized pattern of wild-type neurons. The dendritic spine density of mGluR5 KO spiny stellate neurons was significantly higher than in wild-type neurons. Whole-cell electrophysiological recordings detected a significant increase in the frequencies of spontaneous and miniature excitatory postsynaptic events in mGluR5 KO neurons compared with neighboring wild-type neurons. Our mosaic analysis provides strong evidence supporting the cell-autonomous influence of mGluR5 signaling on the functional and anatomical development of cortical glutamatergic neurons. Specifically, mGluR5 is required in cortical glutamatergic neurons for the following processes: (1) the placement of cortical glutamatergic neurons close to TCA clusters; (2) the regulation of dendritic complexity and outgrowth toward TCA clusters; (3) spinogenesis; and (4) tuning of excitatory inputs. <b>SIGNIFICANCE STATEMENT</b> Glutamatergic transmission plays a critical role in cortical circuit formation. Its dysfunction has been proposed as a core factor in the etiology of many neurological diseases. Here we conducted mosaic analysis to reveal the cell-autonomous role of the metabotropic glutamate receptor 5 (mGluR5). We found that mGluR5 is required for several key steps in wiring up the thalamocortical connections to form the cortical somatosensory map. mGluR5-dependent processes during early postnatal brain development affect the following: (1) placement of activity-directed cortical neurons; (2) regulation of polarized dendritic outgrowth toward thalamocortical axons relaying sensory information, (3) synaptogenesis; and (4) development of functional connectivity in spiny stellate neurons. Perturbing mGluR5 expression could lead to abnormal neuronal circuits, which may contribute to neurological and psychiatric disease." @default.
• W2512338506 created "2016-09-16" @default.
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• W2512338506 date "2016-08-24" @default.
• W2512338506 modified "2023-10-03" @default.
• W2512338506 title "mGluR5 Exerts Cell-Autonomous Influences on the Functional and Anatomical Development of Layer IV Cortical Neurons in the Mouse Primary Somatosensory Cortex" @default.
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• W2512338506 doi "https://doi.org/10.1523/jneurosci.1224-16.2016" @default.
• W2512338506 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4995298" @default.
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