Project Detail
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Office of Autism Research Coordination (OARC) logo

Neurexin-neuroligin trans-synaptic interaction in learning and memory  

Autism arises from disturbances in the remodeling and stabilization of synaptic connections between neurons, rather than from their initial formation. Thus, in the previous SFARI funded research, we investigated the role of two autism-implicated genes, neurexin and neuroligin, in the induction and stabilization of learning-induced changes at the synapse to gain critical insights into the mechanisms that underlie autism. Towards that goal, we used two complementary model systems of emotional learning: (1) The gill-withdrawal reflex in the sea slug, Aplysia, which undergoes a simple form of learned-fear and can be studied at the level of individual identified synaptic connections in a reduced culture preparation. We have found Aplysia neurexin and neuroligin genes are important for learning-induced changes in the function and structure of synaptic connections and their stable maintenance. (2) The amygdala, a region in the brain involved in fear memory, which has been found consistently to be affected in individuals with autism. We have found that acute suppression of neuroligin-1 in the amygdala of mice leads to a decrease in the learning-induced strengthening of synaptic connections and to a deficit in fear memory. We propose to extend our study by examining how the interaction between neurexin and neuroligin is modulated by other regulatory molecules at the synapse, such as CPEB and fragile-x mental retardation protein (FMRP), as well as explore the specific molecular cascades for cellular signaling that are recruited by the neurexin and neuroligin interaction. Our proposed studies, which include the characterization of possible interactions between two distinct classes of autism-implicated genes, FMRP and neurexin-neuroligin, should not only provide valuable insights into the dysfunction of remodeling and stabilization at the synapse that may represent important, contributing cellular underpinnings of autism but also increase our understanding of how different genetic factors interact to manifest common clinical characteristics of autism. Project Status
NEW

2010

Funder Simons Foundation
Fiscal Year Funding $100,000.00
Current Award Period 2010-2013
Project Number 177568
Principal Investigator Kandel, Eric
Received ARRA Funding? No
Strategic Plan Question Question 2: How Can I Understand What Is Happening? (Biology)
Subcategory Molecular Pathways
Strategic Plan Objective 2O. Not specific to Question 2 objectives
Federal or Private? Private
Institution Columbia University
State/Country New York
Web Link 1 Neurexin-neuroligin trans-synaptic interaction in learning and memory (External web link)
Web Link 2 No URL available.
Web Link 3 No URL available.
New! History/Related Projects Neurexin-neuroligin trans-synaptic interaction in learning and memory | $200,000.00 | 2009 | 94173
Neurexin-neuroligin trans-synaptic interaction in learning and memory | $100,000.00 | 2010 | 94173