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SYNGAP1 heterozygosity disrupts sensory processing by reducing touch-related activity within somatosensory cortex circuits.
- Source :
-
Nature neuroscience [Nat Neurosci] 2018 Dec; Vol. 21 (12), pp. 1-13. Date of Electronic Publication: 2018 Nov 21. - Publication Year :
- 2018
-
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.
- Subjects :
- Animals
Cognition physiology
Female
Haploinsufficiency
Humans
Male
Mice
Neurons physiology
Patch-Clamp Techniques
Registries
Sensation Disorders physiopathology
Nerve Net physiopathology
Sensation Disorders genetics
Somatosensory Cortex physiopathology
Touch physiology
Touch Perception physiology
ras GTPase-Activating Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1546-1726
- Volume :
- 21
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Nature neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 30455457
- Full Text :
- https://doi.org/10.1038/s41593-018-0268-0