![]() Furthermore, our work also provides a framework for future translational research on age-sensitive targeted interventions. ![]() Our results indicated distinct adolescent-sensitive periods during which stress can sex-dependently confer maximal risks to corticolimbic systems to drive dopamine hyperactivity, which provide critical insights into the neurobiological basis for sex-biased stress-related psychopathologies emphasizing but not limited to schizophrenia. In contrast, female PostP-S only produced vHipp PVI impairments in adults, with the BLA structure and functions largely unaffected. These male selective PreP-S effects were correlated with stress-induced aberrant persistent BLA hyperactivity, dysfunctional prefrontal inhibitory control of BLA neurons, and vHipp/BLA PVI impairments. Specifically, while males were selectively vulnerable to PreP-S-induced adult VTA dopamine neuron and vHipp hyperactivities, females were selectively vulnerable to PostP-S. Overall, we found distinct sex- and exposure age-dependent stress vulnerability. These endpoints were selected based on their well-documented roles in the pathophysiology of psychosis. Using in vivo electrophysiology and immunohistology in rats, we systematically compared the effects of two age-defined adolescent stress paradigms, prepubertal (postnatal day 21-30 PreP-S) and postpubertal (PD41-50 PostP-S) foot-shock and restraint combined stress, on ventral tegmental area (VTA) dopaminergic activity, pyramidal neuron activity in the ventral hippocampus (vHipp) and the basolateral amygdala (BLA), corticoamygdalar functional inhibitory control, and vHipp and BLA parvalbumin interneuron (PVI) impairments. Emerging evidence suggests that age-dependent sensitive windows for childhood trauma are associated more strongly with adult psychosis, but the neurobiological basis and potential sex differences are unknown. Data are shown as mean SEM.Īdolescent stress is a risk factor for schizophrenia. Data from both groups were normalized to the mean of the control group in each respective brain state and pooled. ![]() Inhibitory activity was consistently lower in chABC-treated rats compared with controls across brain states and stimulus-evoked/spontaneous activity. Spontaneous and stimulus-evoked activity in putative inhibitory and excitatory units is shown in right panels. Unit activity is shown before and during visual stimulation of all putative inhibitory (top) and excitatory units (bottom) in both brain states. B, Brain state was classified as synchronized or desynchronized based on the ratio between the LFP power of slow (1-10 Hz) and fast (30-80 Hz) oscillations. Bottom, Corresponding raw LFP trace (the arrow indicates a state transition after approximately six seconds). Top, Spectrogram computed from the LFP (wavelet analysis, log-power color-coded). A, Spontaneous switch of brain state from synchronized (nonattentive) to desynchronized (attentive) state. Population activity varies with brain state.
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