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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.

SUBMITTER: Moyer CE

PROVIDER: S-EPMC4830289 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Developmental Trajectories of Auditory Cortex Synaptic Structures and Gap-Prepulse Inhibition of Acoustic Startle Between Early Adolescence and Young Adulthood in Mice.

Moyer Caitlin E CE Erickson Susan L SL Fish Kenneth N KN Thiels Edda E Penzes Peter P Sweet Robert A RA

Cerebral cortex (New York, N.Y. : 1991) 20150310 5

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 qua ...[more]

PMID: 25759333

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Project description:Background: An increasingly used behavioral paradigm for the objective assessment of a possible tinnitus percept in animal models has been proposed by Turner and coworkers in 2006. It is based on gap-prepulse inhibition (PPI) of the acoustic startle reflex (ASR) and usually referred to as GPIAS. As it does not require conditioning it became the method of choice to study neuroplastic phenomena associated with the development of tinnitus. Objective: It is still controversial if GPIAS is really appropriate for tinnitus screening, as the hypothesis that a tinnitus percept impairs the gap detection ability ("filling-in interpretation" is still questioned. Furthermore, a wide range of criteria for positive tinnitus detection in GPIAS have been used across different laboratories and there still is no consensus on a best practice for statistical evaluation of GPIAS results. Current approaches are often based on simple averaging of measured PPI values and comparisons on a population level without the possibility to perform valid statistics on the level of the single animal. Methods: A total number of 32 animals were measured using the standard GPIAS paradigm with varying number of measurement repetitions. Based on this data further statistical considerations were performed. Results: We here present a new statistical approach to overcome the methodological limitations of GPIAS. In a first step we show that ASR amplitudes are not normally distributed. Next we estimate the distribution of the measured PPI values by exploiting the full combinatorial power of all measured ASR amplitudes. We demonstrate that the amplitude ratios (1-PPI) are approximately lognormally distributed, allowing for parametrical testing of the logarithmized values and present a new statistical approach allowing for a valid and reliable statistical assessment of PPI changes in GPIAS. Conclusion: Based on our statistical approach we recommend using a constant criterion, which does not systematically depend on the number of measurement repetitions, in order to divide animals into a tinnitus and a non-tinnitus group. In particular, we recommend using a constant threshold based on the effect size as criterion, as the effect size, in contrast to the p-value, does not systematically depend on the number of measurement repetitions.

Project description:BackgroundAdolescence is a critical period for the development of eating disorders, but data is lacking on the heterogeneity of their evolution during that time-period. Group-based trajectories can be used to understand how eating disorders emerge and evolve over time. The aim of this study was to identify groups of individuals with distinct levels of eating disorder symptoms between 12 and 20 years and the onset of different types of symptoms. We also studied sex differences in the evolution and course of eating disorder symptoms from early adolescence to adulthood.MethodsUsing archival data from the QLSCD cohort, trajectories of eating disorder symptomatology were estimated from ages 12 to 20 years using semiparametric models. These trajectories included overall eating disorder symptomatology as measured by the SCOFF (Sick, Control, One Stone, Fat, Food), sex, and symptom-specific trajectories.ResultsTwo groups of adolescents following distinct trajectories of eating disorder symptoms were identified. The first trajectory group included 30.9% of youth with sharply rising levels between 12 and 15 years, followed by high levels of symptoms between 15 and 20 years. The second trajectory group included 69.1% of youth with low and stable levels of symptoms between 12 and 20 years. Sex-specific models indicated that the proportion of girls in the high trajectory group was 1.3 times higher than the proportion of boys (42.8% girls vs. 32.3% boys). Trajectories of SCOFF items were similar for loss-of-control eating, feeling overweight, and attributing importance to food. The weight loss item had a different developmental pattern, increasing between 12 and 15 years and then decreasing between 17 and 20 years.ConclusionsThe largest increase in eating disorder symptoms in adolescence is between the ages of 12 and 15 . Yet, most prevention programs start after 15 years of age. Our findings suggest that, unlike common practices, eating disorder prevention programs should aim to start before puberty.

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Dataset Information

Developmental Trajectories of Auditory Cortex Synaptic Structures and Gap-Prepulse Inhibition of Acoustic Startle Between Early Adolescence and Young Adulthood in Mice.

Publications

Developmental Trajectories of Auditory Cortex Synaptic Structures and Gap-Prepulse Inhibition of Acoustic Startle Between Early Adolescence and Young Adulthood in Mice.

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