What is it about?
Prepulse inhibition (PPI) allows assessing schizophrenia-like sensorimotor gating deficits in rodents. Previous studies indicate that PPI is modulated by the medial prefrontal cortex (mPFC), which is in agreement with our findings showing that PPI differences in the Roman rats are associated with divergences in mPFC activity. Here, we explore whether differences in PPI and mPFC activity in male Roman rats can be explained by (i) differences in the activation (c-Fos) of inhibitory neurons (parvalbumin (PV) interneurons); and/or (ii) reduced excitatory drive (PSD-95) to PV interneurons. Our data show that low PPI in the Roman high-avoidance (RHA) rats is associated with reduced activation of PV interneurons. Moreover, the RHA rats exhibit decreased density of both PV interneurons and PSD-95 puncta on active PV interneurons. These findings point to reduced cortical inhibition as a candidate to explain the schizophrenia-like features observed in RHA rats and support the role of impaired cortical inhibition in schizophrenia.
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Why is it important?
The importance of this research lies in its contribution to understanding the neurobiological mechanisms underlying schizophrenia-like sensorimotor gating deficits. By demonstrating that low prepulse inhibition (PPI) in Roman high-avoidance (RHA) rats is associated with reduced activation and density of parvalbumin (PV) interneurons, as well as decreased PSD-95 puncta on active PV interneurons in the medial prefrontal cortex (mPFC), the study provides compelling evidence for the role of impaired cortical inhibition in schizophrenia-like features. This finding is significant because it aligns with the broader understanding of schizophrenia pathophysiology, where disruptions in the excitatory-inhibitory balance and PV interneuron function are implicated. Moreover, it supports the use of PPI as a translational measure for studying schizophrenia in animal models and highlights the mPFC as a key region of interest. Such insights are crucial for developing targeted therapeutic interventions and advancing our understanding of the complex neural circuitry involved in schizophrenia and related disorders.
Perspectives
From a broader perspective, this research offers valuable insights into the intricate relationship between brain structure, function, and behavior in the context of psychiatric disorders. By linking specific neurobiological alterations in the medial prefrontal cortex to observable behavioral deficits in sensorimotor gating, the study bridges the gap between molecular neuroscience and clinical psychiatry. This approach not only enhances our understanding of schizophrenia but also exemplifies the power of translational research in mental health. The findings underscore the importance of investigating inhibitory neurotransmission and cortical microcircuitry in psychiatric disorders, potentially opening new avenues for therapeutic interventions. Furthermore, this research highlights the utility of animal models in studying complex human disorders, demonstrating how carefully selected rodent strains can provide crucial insights into the neural basis of psychiatric symptoms. Ultimately, such studies contribute to a more comprehensive understanding of brain function in health and disease, paving the way for more targeted and effective treatments for schizophrenia and related disorders.
Carles Tapias Espinosa
Read the Original
This page is a summary of: Decreased activation of parvalbumin interneurons in the medial prefrontal cortex in intact inbred Roman rats with schizophrenia-like reduced sensorimotor gating, Behavioural Brain Research, February 2023, Elsevier,
DOI: 10.1016/j.bbr.2022.114113.
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