Role of neurexin in the amygdala and associated fear memory

Eric Kandel, Ph.D.
Columbia University

Individuals with autism have deficits in social and emotional learning. The amygdala, a region of the brain involved in orchestrating emotion and emotional memory, is affected in individuals with autism. The nature of the dysfunction is not well characterized, however. Eric Kandel and his colleagues at Columbia University Medical Center aim to examine the role of an autism-implicated protein, neurexin, at synapses — the connections between nerve cells — in the amygdala. They also plan to investigate how neurexin is involved in fear memory, a function that is associated with the amygdala.

Kandel and his colleagues have found that neurexin and its binding partner neuroligin, which is also implicated in autism, are important for inducing and stabilizing synaptic changes related to learned fear. For that study, they used the invertebrate model system Aplysia, or sea slugs. What’s more, they have found that acute suppression of neuroligin-1 in the rodent amygdala leads to a decrease in learning-induced strengthening of the connections between nerve cells and to a deficit in fear conditioning, a form of emotional memory.

As a next step, Kandel’s team aims to investigate how virally mediated acute suppression of neurexin in the mouse amygdala affects learning-induced changes in synaptic connections. This would involve electrophysiological studies and tests of animal behavior, specifically of fear conditioning.

Detailed studies of autism-related genes, such as neurexin and neuroligin, are likely to be highly informative about the nature of dysfunction associated with autism, particularly in the amygdala, the researchers say.