Hypersensitivity to Distractors in Fragile X Syndrome from Loss of Modulation of Cortical VIP Interneurons
Abstract
Attention deficit is one of the most prominent and disabling symptoms in Fragile X syndrome (FXS). Hypersensitivity to sensory stimuli contributes to attention difficulties by overwhelming and/or distracting affected individuals, which disrupts activities of daily living at home and learning at school. We find that auditory or visual distractors selectively impair visual discrimination performance in humans and mice with FXS but not in typically developing controls. In both species, males and females were examined. Vasoactive intestinal polypeptide (VIP) neurons were significantly modulated by incorrect responses in the poststimulus period during early distractor trials in WT mice, consistent with their known role as error signals. Strikingly, however, VIP cells fromFmr1−/−mice showed little modulation in error trials, and this correlated with their poor performance on the distractor task. Thus, VIP interneurons and their reduced modulatory influence on pyramidal cells could be a potential therapeutic target for attentional difficulties in FXS.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 10, 2023
- Source ID
- 10.1523/jneurosci.0571-23.2023
Entities
People
- Anubhuti Goel
- Carlos Portera-Cailliau
- Craig Erickson
- Ernest Pedapati
- Gunvant Chaudhari
- Jessica Robledo
- Lauren M. Schmitt
- Lisa De Stefano
- Noorhan Rahmatullah
- Sam Post
Organizations
- Brain & Behavior Research Foundation
- National Center for Medical Rehabilitation Research
- National Institute of Neurological Disorders and Stroke
- United States Department of Defense