A Role for PGC-1α in Transcription and Excitability of Neocortical and Hippocampal Excitatory Neurons
| Autor: | Aundrea F. Bartley, Elena W Adlaf, Andrew S. Bohannon, Peter J. Detloff, David K. Crossman, T. van Groen, Linda Overstreet-Wadiche, Laura J. McMeekin, Lynn E. Dobrunz, Rita M. Cowell, John J. Hablitz, Stephanie N. Fox, S.M. Boas |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Interneuron Neocortex Neurotransmission Biology Hippocampal formation Inhibitory postsynaptic potential Hippocampus Article Mice 03 medical and health sciences chemistry.chemical_compound Glutamatergic 0302 clinical medicine Interneurons medicine Animals Neurotransmitter Mice Knockout Neurons General Neuroscience Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha 030104 developmental biology medicine.anatomical_structure nervous system chemistry Neuron Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience |
| ISSN: | 0306-4522 |
| Popis: | The transcriptional coactivator peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a critical regulator of genes involved in neuronal metabolism, neurotransmission, and morphology. Reduced PGC-1α expression has been implicated in several neurological and psychiatric disorders. An understanding of PGC-1α’s roles in different cell types will help determine the functional consequences of PGC-1α dysfunction and/or deficiency in disease. Reports from our laboratory and others suggest a critical role for PGC-1α in inhibitory neurons with high metabolic demand such as fast-spiking interneurons. Here, we document a previously unrecognized role for PGC-1α in maintenance of gene expression programs for synchronous neurotransmitter release, structure, and metabolism in neocortical and hippocampal excitatory neurons. Deletion of PGC-1α from these neurons caused ambulatory hyperactivity in response to a novel environment and enhanced glutamatergic transmission in neocortex and hippocampus, along with reductions in mRNA levels from several PGC-1α neuron-specific target genes. Given the potential role for a reduction in PGC-1α expression or activity in Huntington Disease (HD), we compared reductions in transcripts found in the neocortex and hippocampus of these mice to that of an HD knock-in model; few of these transcripts were reduced in this HD model. These data provide novel insight into the function of PGC-1α in glutamatergic neurons and suggest that it is required for the regulation of structural, neurosecretory, and metabolic genes in both glutamatergic neuron and fast-spiking interneuron populations in a region-specific manner. These findings should be considered when inferring the functional relevance of changes in PGC-1α gene expression in the context of disease. |
| Databáze: | OpenAIRE |
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