Healthy cognitive and emotional functioning relies on a balance between excitatory and inhibitory neurotransmission in the prefrontal cortex (PFC). This balance is largely established during early postnatal and adolescent developmental periods by maturation of the γ-aminobutyric acid (GABA) system, including increased density of parvalbumin (PV) cells and perineuronal nets (PNNs). Genetic and/or environmental factors during adolescence can disrupt GABAergic maturation and lead to behavioral dysfunction in adulthood. The present study examined the interaction between chronic mild stress during adolescence and genetic deficiency of neuronal Per-Arnt-Sim domain 4 (Npas4), a brain-specific transcription factor that regulates inhibitory neurotransmission and that contributes to adolescent prefrontal GABAergic maturation. Male Npas4 wild-type (WT) and heterozygous (HET) mice were exposed to adolescent chronic stress and tested in adulthood for cognitive function using the attention set shifting task. When Npas4 deficiency was combined with adolescent stress, mice displayed impaired cognitive flexibility as observed by poor performance on the extra-dimensional set shift task. At the cellular level, adolescent stress increased the perc...Continue Reading
Neuronal activity in primate visual cortex assessed by immunostaining for the transcription factor Zif268
Attentional set-shifting in mice: modification of a rat paradigm, and evidence for strain-dependent variation
Homeostatic scaling of vesicular glutamate and GABA transporter expression in rat neocortical circuits
Social isolation rearing-induced impairment of the hippocampal neurogenesis is associated with deficits in spatial memory and emotion-related behaviors in juvenile mice
Inactivation of the medial prefrontal cortex of the rat impairs strategy set-shifting, but not reversal learning, using a novel, automated procedure
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Acute stress enhances glutamatergic transmission in prefrontal cortex and facilitates working memory
Postnatal developmental trajectories of neural circuits in the primate prefrontal cortex: identifying sensitive periods for vulnerability to schizophrenia
Transcriptional suppression of the neuronal PAS domain 4 (Npas4) gene by stress via the binding of agonist-bound glucocorticoid receptor to its promoter
Npas4: a neuronal transcription factor with a key role in social and cognitive functions relevant to developmental disorders
Differential regulation of parvalbumin and calretinin interneurons in the prefrontal cortex during adolescence
Developmental pattern of perineuronal nets in the human prefrontal cortex and their deficit in schizophrenia
Long-term changes in cognitive bias and coping response as a result of chronic unpredictable stress during adolescence
Activity-dependent NPAS4 expression and the regulation of gene programs underlying plasticity in the central nervous system
Altered cortical expression of GABA-related genes in schizophrenia: illness progression vs developmental disturbance
Npas4 regulates excitatory-inhibitory balance within neural circuits through cell-type-specific gene programs
Pentraxins coordinate excitatory synapse maturation and circuit integration of parvalbumin interneurons
Altered Markers of Cortical γ-Aminobutyric Acid Neuronal Activity in Schizophrenia: Role of the NARP Gene
Parvalbumin-positive interneurons of the prefrontal cortex support working memory and cognitive flexibility
Reduced Labeling of Parvalbumin Neurons and Perineuronal Nets in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia
Anxiety Evokes Hypofrontality and Disrupts Rule-Relevant Encoding by Dorsomedial Prefrontal Cortex Neurons
Wisteria Floribunda Agglutinin-Labeled Perineuronal Nets in the Mouse Inferior Colliculus, Thalamic Reticular Nucleus and Auditory Cortex
Pathological Basis for Deficient Excitatory Drive to Cortical Parvalbumin Interneurons in Schizophrenia
Stress and the adolescent brain: Amygdala-prefrontal cortex circuitry and ventral striatum as developmental targets
Sustained Attentional States Require Distinct Temporal Involvement of the Dorsal and Ventral Medial Prefrontal Cortex
The transcription factor Npas4 contributes to adolescent development of prefrontal inhibitory circuits, and to cognitive and emotional functions: Implications for neuropsychiatric disorders
Adolescent maturation of the prefrontal cortex: Role of stress and sex in shaping adult risk for compromise
Downregulation of Npas4 in parvalbumin interneurons and cognitive deficits after neonatal NMDA receptor blockade: relevance for schizophrenia
Chronic treatment with the antipsychotic drug blonanserin modulates the responsiveness to acute stress with anatomical selectivity.
Antioxidant treatment ameliorates prefrontal hypomyelination and cognitive deficits in a rat model of schizophrenia.
Perineuronal nets are under the control of type-5 metabotropic glutamate receptors in the developing somatosensory cortex.
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