Accession Number:

ADA591041

Title:

Altered Gastrointestinal Function in the Neuroligin-3 Mouse Model of Autism

Descriptive Note:

Annual rept. 30 Sep 2012-29 Sep 2013

Corporate Author:

MELBOURNE UNIV PARKVILLE (AUSTRALIA)

Personal Author(s):

Report Date:

2013-10-01

Pagination or Media Count:

81.0

Abstract:

Up to 80 of ASD patients exhibit gastrointestinal GI problems, but the underlying mechanisms are unknown. Many ASD associated mutations modify synaptic proteins and hence alter synaptic function in the brain. We propose that some of these mutations also alter the enteric nervous system ENS to produce bowel disorders. NL3 mice express a neuroligin-3 mutation identified in ASD patients and are more responsive to the GABA neurotransmission in the brain. This work aims to study the spatiotemporal distribution patterns of NL3 in gut tissue from these mice in order to determine biological mechanisms contributing to GI dysfunction in patients with ASD. We will also use intracellular recording techniques to determine which cell types are responsive to GABA in the myenteric plexus and if responses differ in WT and NL3 mutant colon. We have localized neuroligin 3 protein to a subset of neurons in the mouse colon and jejunal myenteric plexus. Unexpectedly, we show localization of neuroligin-3 protein to presynaptic specializations in the myenteric plexus in both the colon and the jejunum of the mouse. Importantly, we have demonstrated that S neurons in the proximal myenteric plexus of the mouse colon are depolarized in response to local application of GABA.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE