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GIT1 regulates synaptic structural plasticity underlying learning

2018; Public Library of Science; Volume: 13; Issue: 3 Linguagem: Inglês

10.1371/journal.pone.0194350

1932-6203

Amanda C. Martyn, Krisztián Tóth, Robert Schmalzigaug, Nathan G. Hedrick, Ramona M. Rodriguiz, Ryohei Yasuda, William C. Wetsel, Richard T. Premont,

Cellular transport and secretion

The signaling scaffold protein GIT1 is expressed widely throughout the brain, but its function in vivo remains elusive. Mice lacking GIT1 have been proposed as a model for attention deficit-hyperactivity disorder, due to alterations in basal locomotor activity as well as paradoxical locomotor suppression by the psychostimulant amphetamine. Since we had previously shown that GIT1-knockout mice have normal locomotor activity, here we examined GIT1-deficient mice for ADHD-like behavior in more detail, and find neither hyperactivity nor amphetamine-induced locomotor suppression. Instead, GIT1-deficient mice exhibit profound learning and memory defects and reduced synaptic structural plasticity, consistent with an intellectual disability phenotype. We conclude that loss of GIT1 alone is insufficient to drive a robust ADHD phenotype in distinct strains of mice. In contrast, multiple learning and memory defects have been observed here and in other studies using distinct GIT1-knockout lines, consistent with a predominant intellectual disability phenotype related to altered synaptic structural plasticity.