Affiliation:
1. Department of Neurology and Neurological Sciences, Stanford University
2. Department of Genetics, Harvard Medical School
3. Program in Neurobiology and Department of Neurology, Boston Children's Hospital
Abstract
Absence seizures are characterized by brief periods of unconsciousness accompanied by lapses in motor function that can occur hundreds of times throughout the day. Outside of these frequent moments of unconsciousness, approximately a third of people living with the disorder experience treatment-resistant attention impairments. Convergent evidence suggests prefrontal cortex (PFC) dysfunction may underlie attention impairments in affected patients. To examine this, we use a combination of slice physiology, fiber photometry, electrocorticography (ECoG), optogenetics, and behavior in the Scn8a+/-mouse model of absence epilepsy. Attention function was measured using a novel visual attention task where a light cue that varied in duration predicted the location of a food reward. In Scn8a+/-mice, we find altered parvalbumin interneuron (PVIN) output in the medial PFC (mPFC) in vitro and PVIN hypoactivity along with reductions in gamma power during cue presentation in vivo. This was associated with poorer attention performance in Scn8a+/-mice that could be rescued by gamma-frequency optogenetic stimulation of PVINs. This highlights cue-related PVIN activity as an important mechanism for attention and suggests PVINs may represent a therapeutic target for cognitive comorbidities in absence epilepsy.
Funder
National Institute of Mental Health
National Institute of Neurological Disorders and Stroke
Stanford University
National Institute of Neurological Disorders & Stroke
Publisher
eLife Sciences Publications, Ltd
Subject
General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience
Reference104 articles.
1. Attention function and dysfunction in autism;Allen;Frontiers in Bioscience,2001
2. Fmri “ deactivation ” of the posterior cingulate during generalized spike and wave;Archer;NeuroImage,2003
3. Prefrontal modulation of visual processing in humans;Barceló;Nature Neuroscience,2000
4. Recognition memory for objects, place, and temporal order: a disconnection analysis of the role of the medial prefrontal cortex and perirhinal cortex;Barker;The Journal of Neuroscience,2007
5. Absence epilepsy: characteristics, pathophysiology, attention impairments, and the related risk of accidents: A narrative review;Barone;Epilepsy & Behavior,2020
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