Dysfunctional hippocampal-prefrontal network underlies a multidimensional neuropsychiatric phenotype following early-life seizure.

Brain disturbances during development can have a lasting impact on neural function and behavior. Seizures during this critical period are linked to significant long-term consequences such as neurodevelopmental disorders, cognitive impairments, and psychiatric symptoms, resulting in a complex spectrum of multimorbidity. The hippocampus-prefrontal cortex (HPC-PFC) circuit emerges as a potential common link between such disorders. However, the mechanisms underlying these outcomes and how they relate to specific behavioral alterations are unclear. We hypothesized that specific dysfunctions of hippocampal-cortical communication due to early-life seizure would be associated with distinct behavioral alterations observed in adulthood. Here, we performed a multilevel study to investigate behavioral, electrophysiological, histopathological, and neurochemical long-term consequences of early-life Status epilepticus in male rats. We show that adult animals submitted to early-life seizure (ELS) present working memory impairments and sensorimotor disturbances, such as hyperlocomotion, poor sensorimotor gating, and sensitivity to psychostimulants despite not exhibiting neuronal loss. Surprisingly, cognitive deficits were linked to an aberrant increase in the HPC-PFC long-term potentiation (LTP) in a U-shaped manner, while sensorimotor alterations were associated with heightened neuroinflammation, as verified by glial fibrillary acidic protein (GFAP) expression, and altered dopamine neurotransmission. Furthermore, ELS rats displayed impaired HPC-PFC theta-gamma coordination and an abnormal brain state during active behavior resembling rapid eye movement (REM) sleep oscillatory dynamics. Our results point to impaired HPC-PFC functional connectivity as a possible pathophysiological mechanism by which ELS can cause cognitive deficits and psychiatric-like manifestations even without neuronal loss, bearing translational implications for understanding the spectrum of multidimensional developmental disorders linked to early-life seizures.

Multidimensional behavioral profiles associated with resilience and susceptibility after inescapable stress.

Clinical depression is characterized by multiple concurrent symptoms, manifesting as a complex heterogeneous condition. Although some well-established classical behavioral assessments are widespread in rodent models, it remains uncertain whether rats also display stress-induced depression-related phenotypes in a multidimensional manner, i.e., simultaneous alterations in multiple behavioral tests. Here, we investigated multivariate patterns and profiles of depression-related behavioral traits in male Wistar rats subjected to inescapable footshocks (IS) or no-shocks (NS), followed by a comprehensive battery of behavioral tests and ethological characterization. We observed generalized stronger intra-test but weaker inter-test correlations. However, feature clustering of behavioral measures successfully delineated variables linked to resilience and susceptibility to stress. Accordingly, a noteworthy covariation pattern emerged, characterized by increased open field locomotion, reduced time in the elevated plus maze open arms, lower sucrose preference, and increased shuttle box escape failures that consistently differentiated IS from NS. Surprisingly there is little contribution from forced swim. In addition, individual clustering revealed a diversity of behavioral profiles, naturally separating NS and IS, including subpopulations entirely characterized by resilience or susceptibility. In conclusion, our study elucidates intricate relationships among classical depression-related behavioral measures, highlighting multidimensional individual variability. Our work emphasizes the importance of a multivariate framework for behavioral assessment in animal models to understand stress-related neuropsychiatric disorders.

Anxiety and functional impairment affects undergraduate psychology students' learning in remote emergency teaching during the COVID-19 pandemic.

This study aimed to explore the impact of anxiety and functional impairment measures on a sample of undergraduate psychology students. Learning performance was evaluated during the emergency remote teaching during the first wave and in the post-vaccination period of the COVID-19 pandemic in Brazil. Data modeling revealed that psychometric indicators of severe anxiety and severe functional impairment predicted students with lower learning performance in pairs of pre- and post-test multiple-choice questions. This is the first study to highlight the association between measures of generalized anxiety and functional impairment having a deleterious impact on students' learning performance. This manuscript highlights that educational policies should be designed to deal with students' mental health under stressful situations.

Parvalbumin Role in Epilepsy and Psychiatric Comorbidities: From Mechanism to Intervention.

Parvalbumin is a calcium-binding protein present in inhibitory interneurons that play an essential role in regulating many physiological processes, such as intracellular signaling and synaptic transmission. Changes in parvalbumin expression are deeply related to epilepsy, which is considered one of the most disabling neuropathologies. Epilepsy is a complex multi-factor group of disorders characterized by periods of hypersynchronous activity and hyperexcitability within brain networks. In this scenario, inhibitory neurotransmission dysfunction in modulating excitatory transmission related to the loss of subsets of parvalbumin-expressing inhibitory interneuron may have a prominent role in disrupted excitability. Some studies also reported that parvalbumin-positive interneurons altered function might contribute to psychiatric comorbidities associated with epilepsy, such as depression, anxiety, and psychosis. Understanding the epileptogenic process and comorbidities associated with epilepsy have significantly advanced through preclinical and clinical investigation. In this review, evidence from parvalbumin altered function in epilepsy and associated psychiatric comorbidities were explored with a translational perspective. Some advances in potential therapeutic interventions are highlighted, from current antiepileptic and neuroprotective drugs to cutting edge modulation of parvalbumin subpopulations using optogenetics, designer receptors exclusively activated by designer drugs (DREADD) techniques, transcranial magnetic stimulation, genome engineering, and cell grafting. Creating new perspectives on mechanisms and therapeutic strategies is valuable for understanding the pathophysiology of epilepsy and its psychiatric comorbidities and improving efficiency in clinical intervention.