Talk abstracts
Talk on Tuesday 04:30-04:45pm submitted by Chloe Page
Npas4-deficient mice lack homeostatic resilience against mild stress in adolescence and show impaired cognitive flexibility in adulthood.
Chloe E. Page (Neuroscience Graduate Program), Jonathan Alexander (Department of Neuroscience; The Ohio State University), Laurence Coutellier (Department of Neuroscience, Department of Psychology; The Ohio State University)
Abstract:
The prefrontal cortex (PFC) relies on a balance of excitatory and inhibitory neurotransmission to integrate perceptions, memories, and emotions toward guiding goal-directed behavior. This excitatory/inhibitory (E/I) balance is largely established during early postnatal and adolescent development and depends on activity-dependent maturation of the GABAergic system. Genetic and/or environmental factors during adolescence can disrupt E/I balance and maturation and lead to cognitive and emotional dysfunction in adulthood. The present study examined in mice the interaction between chronic mild stress (CMS) during adolescence [postnatal day – PND – 28-42] and deficiency of Npas4, a brain-specific transcription factor that regulates the formation and maintenance of inhibitory synapses in response to excitation. Npas4 wild type (WT) and heterozygous (HET) mice were tested and brains were collected in adulthood [PND 63-68]. Anxiety behaviors were measured in the elevated plus maze and open field test, and PFC-dependent cognitive function was measured using the attentional set shifting task (ASST). Behaviorally, adolescent CMS lead to increased anxiety in adulthood, an effect that was not mediated by Npas4. Only the Npas4 HET mice showed impaired cognitive flexibility in adulthood following adolescent stress, as observed by poor performance on the extradimensional set shift trial of the ASST. At the cellular level, stress alone decreased c-fos expression in the basolateral amygdala and increased numbers of parvalbumin cells surrounded by perineuronal nets in the ventral PFC of adults. HET mice who underwent adolescent stress did not show these same cellular changes. Together, these results suggest that WT mice are capable of exerting homeostatic compensatory changes that protect against stress-induced cognitive impairment: an ability that Npas4 HET mice lack. This demonstrates a novel gene by environment interaction that influences E/I balance and resilience vs. vulnerability to stress, with implications for adolescent onset disorders like schizophrenia.
References:
Negrón-Oyarzo et al. 2016. Neural Plast. Article ID 7539065.
Hoftman and Lewis. 2011. Schiz Bull. 37: 493-503.
Bitanihirwe and Woo. 2014. Neurosci Biobehav Rev. 45: 85-99.
Spiegel et al. 2014. Cell. 157: 1216-1229.
Coutellier et al. 2015. Behav. Brain Res. 295: 17-25.
Coutellier et al. 2012. PLoS One. 7(9):e46604.
Heisler et al. 2015. J Vis Exp. 96:e51944.
Izquierdo et al. 2013. J Neurosci. 33(9):4105-4109.
Wassum and Izquierdo. 2015. Neu Bio Rev. 57:271-283.
Keywords: cognitive flexibility, perineuronal nets, psychological stress