title: Developmental changes in expression of inhibitory neuronal proteins in the Fragile X Syndrome mouse basolateral amygdala.
abstract: In humans, Fragile X Syndrome (FXS) is characterized by enhanced fear, hyperactivity, social anxiety, and, in a subset of individuals, autism. Many of the emotional and social deficits point to defects in the amygdala. We have previously shown defects in inhibitory neuron drive onto excitatory projection neurons in the basolateral amygdala (BLA) of juvenile Fmr1(-/y) knockout (KO) mice. Using pharmacological approaches, we have also previously revealed dynamic functional deficits in α1, α2, and α3 subunit-containing GABAA receptors (GABAARs α1, α2, and α3) during early postnatal development. In this study, we sought to determine whether these defects in GABAAR function are accompanied by changes in protein expression of GABAARs α1, α2, and α3 and the post-synaptic GABAAR-clustering protein gephyrin. Interestingly, we found that while the expression of these proteins did not significantly differ between wildtype (WT) and KO mice at each time point, the timing of developmental expression of GABAAR α1, α2, and gephyrin was altered. Collectively, these data reveal novel defects in inhibitory synapse protein expression during critical periods of early postnatal development that could contribute to observed inhibitory neurotransmission deficits in the KO mouse BLA.
authors.affiliation: Center for Neuroscience Research, Children's National Medical Center, 111 Michigan Ave., Washington DC 20010, USA; Department of Biology, University of Maryland, College Park, MD 20742, USA.
authors.forename: Sebila
authors.initials: S
authors.lastname: Kratovac
authors.forename: Joshua G
authors.initials: JG
authors.lastname: Corbin
mesh_terms: D000679:Amygdala / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D005600:Fragile X Syndrome / Q000378:metabolism* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D011963:Receptors, GABA-A; C497684:Fmr1 protein, mouse
keywords: Autism; Basolateral amygdala; Development; Fragile X Syndrome; GABA(A) receptor; Inhibitory synapse