Identification of mechanisms which increase deep sleep could lead to novel treatments which promote the restorative effects of sleep. Here, we show that knockdown of the α3 GABA-receptor subunit from parvalbumin neurons in the thalamic reticular nucleus using CRISPR-Cas9 gene editing increased the thalamocortical delta (1.5-4 Hz) oscillations which are implicated in many health-promoting effects of sleep. Inhibitory synaptic currents in thalamic reticular parvalbumin neurons were strongly reduced in vitro. Further analysis revealed that delta power in long NREM bouts prior to NREM-REM transitions was preferentially affected by deletion of α3 subunits. Our results identify a role for GABA receptors on thalamic reticular nucleus neurons and suggest antagonism of α3 subunits as a strategy to enhance delta activity during sleep.
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http://dx.doi.org/10.1038/s41467-022-29852-x | DOI Listing |
Front Mol Neurosci
December 2024
Laboratory of Veterinary Hygiene, Faculty of Veterinary Medicine, Graduate School of Infectious Diseases, Hokkaido University, Sapporo, Japan.
The accumulation of a disease-specific isoform of prion protein (PrP) and histopathological lesions, such as neuronal loss, are unevenly distributed in the brains of humans and animals affected with prion diseases. This distribution varies depending on the diseases and/or the combinations of prion strain and experimental animal. The brain region-dependent distribution of PrP and neuropathological lesions suggests a neuronal cell-type-dependent prion propagation and vulnerability to prion infection.
View Article and Find Full Text PDFJ Comput Neurosci
December 2024
Department of Applied Mathematics, and Centre for Theoretical Neuroscience, University of Waterloo, 200 University Avenue W, Waterloo, N2L 3G1, ON, Canada.
Childhood absence epilepsy (CAE) is a paediatric generalized epilepsy disorder with a confounding feature of resolving in adolescence in a majority of cases. In this study, we modelled how the small-scale (synapse-level) effect of progesterone metabolite allopregnanolone induces a large-scale (network-level) effect on a thalamocortical circuit associated with this disorder. In particular, our goal was to understand the role of sex steroid hormones in the spontaneous remission of CAE.
View Article and Find Full Text PDFJ Neurophysiol
December 2024
Department of Biological Sciences, Lehigh University 111 Research Drive, Bethlehem, PA 18015 USA.
The thalamic reticular nucleus (TRN) is a thin shell of gap junction coupled GABAergic inhibitory neurons that regulate afferent sensory relay of the thalamus. The TRN receives dopaminergic innervation from the midbrain, and it is known to express high concentrations of D1 and D4 receptors. Although dopaminergic modulation of presynaptic inputs to TRN has been described, the direct effect of dopamine on TRN neurons and its electrical synapses is largely unknown.
View Article and Find Full Text PDFCells
November 2024
Department of Psychology, University of Florida, Gainesville, FL 32603, USA.
Restricted repetitive behaviors (RRB) encompass a variety of inflexible behaviors, which are diagnostic for autism spectrum disorder (ASD). Despite being requisite diagnostic criteria, the neurocircuitry of these behaviors remains poorly understood, limiting treatment development. Studies in translational animal models show environmental enrichment (EE) reduces the expression of RRB, although the underlying mechanisms are largely unknown.
View Article and Find Full Text PDFPLoS Comput Biol
December 2024
Department for Integrative and Computational Neuroscience, Paris-Saclay Institute of Neuroscience, Saclay, France.
The thalamus is the brain's central relay station, orchestrating sensory processing and cognitive functions. However, how thalamic function depends on internal and external states, is not well understood. A comprehensive understanding would necessitate the integration of single cell dynamics with their collective behavior at population level.
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