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Nat Neurosci. 2018 Dec;21(12):1-13. doi: 10.1038/s41593-018-0268-0. Epub 2018 Nov 21.

SYNGAP1 heterozygosity disrupts sensory processing by reducing touch-related activity within somatosensory cortex circuits.

Author information

1
Department of Neuroscience, Scripps Florida, Jupiter, FL, USA.
2
Department of Drug Discovery, Moffitt Cancer Center, Tampa, FL, USA.
3
Bridge-the-GAP Educational Research Foundation, Cyprus, TX, USA.
4
Max Planck Florida Institute for Neuroscience, Jupiter, FL, USA.
5
Jan and Dan Duncan Neurological Research Institute and Department of Pediatrics, Division of Neurology and Developmental Neuroscience, Baylor College of Medicine, Houston, TX, USA.
6
Department of Molecular Medicine, Scripps Florida, Jupiter, Fl, USA.
7
Department of Neuroscience, Scripps Florida, Jupiter, FL, USA. gavin@scripps.edu.
8
Department of Molecular Medicine, Scripps Florida, Jupiter, Fl, USA. gavin@scripps.edu.

Abstract

In addition to cognitive impairments, neurodevelopmental disorders often result in sensory processing deficits. However, the biological mechanisms that underlie impaired sensory processing associated with neurodevelopmental disorders are generally understudied and poorly understood. We found that SYNGAP1 haploinsufficiency in humans, which causes a sporadic neurodevelopmental disorder defined by cognitive impairment, autistic features, and epilepsy, also leads to deficits in tactile-related sensory processing. In vivo neurophysiological analysis in Syngap1 mouse models revealed that upper-lamina neurons in somatosensory cortex weakly encode information related to touch. This was caused by reduced synaptic connectivity and impaired intrinsic excitability within upper-lamina somatosensory cortex neurons. These results were unexpected, given that Syngap1 heterozygosity is known to cause circuit hyperexcitability in brain areas more directly linked to cognitive functions. Thus, Syngap1 heterozygosity causes a range of circuit-specific pathologies, including reduced activity within cortical neurons required for touch processing, which may contribute to sensory phenotypes observed in patients.

PMID:
30455457
PMCID:
PMC6309426
DOI:
10.1038/s41593-018-0268-0
[Indexed for MEDLINE]
Free PMC Article

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