Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Neuroligin1 drives synaptic and behavioral maturation through intracellular interactions.

In vitro studies suggest that the intracellular C terminus of Neuroligin1 (NL1) could play a central role in the maturation of excitatory synapses. However, it is unknown how this activity affects synapses in vivo, and whether it may impact the development of complex behaviors. To determine how NL1 influences the state of glutamatergic synapses in vivo, we compared the synaptic and behavioral phenotypes of mice overexpressing a full-length version of NL1 (NL1FL) with mice overexpressing a version missing part of the intracellular domain (NL1ΔC). We show that overexpression of full-length NL1 yielded an increase in the proportion of synapses with mature characteristics and impaired learning and flexibility. In contrast, the overexpression of NL1ΔC increased the number of excitatory postsynaptic structures and led to enhanced flexibility in mnemonic and social behaviors. Transient overexpression of NL1FL revealed that elevated levels are not necessary to maintain synaptic and behavioral states altered earlier in development. In contrast, overexpression of NL1FL in the fully mature adult was able to impair normal learning behavior after 1 month of expression. These results provide the first evidence that NL1 significantly impacts key developmental processes that permanently shape circuit function and behavior, as well as the function of fully developed neural circuits. Overall, these manipulations of NL1 function illuminate the significance of NL1 intracellular signaling in vivo, and enhance our understanding of the factors that gate the maturation of glutamatergic synapses and complex behavior. This has significant implications for our ability to address disorders such as autism spectrum disorders.

Pubmed ID: 23719805 RIS Download

Mesh terms: Animals | Auditory Cortex | Behavior, Animal | Blotting, Western | Cell Adhesion Molecules, Neuronal | Dendritic Spines | Doxycycline | Electrophysiological Phenomena | Green Fluorescent Proteins | Humans | Image Processing, Computer-Assisted | Immunohistochemistry | Learning Disorders | Maze Learning | Mice | Mice, Transgenic | Microscopy, Confocal | Psychomotor Performance | Recognition (Psychology) | Second Messenger Systems | Social Behavior | Social Dominance | Synapses | Synaptosomes

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIMH NIH HHS, Id: T32 MH018882
  • Agency: NINDS NIH HHS, Id: R01 NS065795
  • Agency: NIDCD NIH HHS, Id: R01 DC011379
  • Agency: NIMH NIH HHS, Id: R01 MH081935
  • Agency: NICHD NIH HHS, Id: R25 HD070817
  • Agency: Autism Speaks, Id: AS1368
  • Agency: NIMH NIH HHS, Id: T32 MH18882-22

Antibody Registry (Reagent, Antibodies)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.