title: Developmental Trajectories of Auditory Cortex Synaptic Structures and Gap-Prepulse Inhibition of Acoustic Startle Between Early Adolescence and Young Adulthood in Mice.
abstract: Cortical excitatory and inhibitory synapses are disrupted in schizophrenia, the symptoms of which often emerge during adolescence, when cortical excitatory synapses undergo pruning. In auditory cortex, a brain region implicated in schizophrenia, little is known about the development of excitatory and inhibitory synapses between early adolescence and young adulthood, and how these changes impact auditory cortex function. We used immunohistochemistry and quantitative fluorescence microscopy to quantify dendritic spines and GAD65-expressing inhibitory boutons in auditory cortex of early adolescent, late adolescent, and young adult mice. Numbers of spines decreased between early adolescence and young adulthood, during which time responses increased in an auditory cortex-dependent sensory task, silent gap-prepulse inhibition of the acoustic startle reflex (gap-PPI). Within-bouton GAD65 protein and GAD65-expressing bouton numbers decreased between late adolescence and young adulthood, a delay in onset relative to spine and gap-PPI changes. In mice lacking the spine protein kalirin, there were no significant changes in spine number, within-bouton GAD65 protein, or gap-PPI between adolescence and young adulthood. These results illustrate developmental changes in auditory cortex spines, inhibitory boutons, and auditory cortex function between adolescence and young adulthood, and provide insights into how disrupted adolescent neurodevelopment could contribute to auditory cortex synapse pathology and auditory impairments.
authors.affiliation: Center for Neuroscience Translational Neuroscience Program, Department of Psychiatry.
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: Moyer
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Erickson
authors.affiliation: Center for Neuroscience Translational Neuroscience Program, Department of Psychiatry.
authors.forename: Kenneth N
authors.initials: KN
authors.lastname: Fish
authors.affiliation: Center for Neuroscience Department of Neurobiology.
authors.forename: Edda
authors.initials: E
authors.lastname: Thiels
authors.affiliation: Department of Physiology Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Penzes
authors.affiliation: Center for Neuroscience Translational Neuroscience Program, Department of Psychiatry Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA Mental Illness Research, Education, and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Sweet
mesh_terms: D000818:Animals; D001303:Auditory Cortex / Q000254:growth & development* / Q000502:physiology*; D049229:Dendritic Spines / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D065808:Prepulse Inhibition / Q000502:physiology*; D013216:Reflex, Startle; D012559:Schizophrenia / Q000503:physiopathology; D013569:Synapses / Q000502:physiology*
chemical_list: D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2
keywords: GAD65; VGluT1; dendritic spines; kalirin; spinophilin