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Published on: March 23, 2011
Developmental Age Differentially Mediates the Calcium-Binding Protein Parvalbumin in the Rat: Evidence for a
Jennifer A Honeycutt1, Kevin M Keary Iii, Vanessa M Kania
1Department of Psychology, Division of Behavioral Neuroscience, University of Connecticut, Storrs, Conn., USA.
Insights
Local circuit parvalbumin (PV) neurons are crucial for brain development and function. This study found PV+ cell counts decrease with age in the hippocampus but increase in the prefrontal cortex of naïve rats.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Cell Biology
Background:
- Local circuit GABAergic neurons, particularly parvalbumin (PV)-containing basket cells, are vital for neocortical circuit development, function, and pathology.
- Decreased PV expression is observed in human schizophrenia brains and ketamine-treated animal models, but conflicting results question PV's utility as a biomarker.
- A systematic characterization of normative PV expression during development in naïve rodent tissue is lacking.
Purpose of the Study:
- To investigate developmental changes in parvalbumin (PV) cell distribution across different brain regions in pharmacologically and behaviorally naïve rats.
- To establish baseline PV expression patterns to better understand its role in neuropathology and inform animal models.
Main Methods:
- Quantified PV+ cell counts across the septotemporal axis of hippocampal subregions (CA1, CA3, DG) and cortical areas (retrosplenial, somatosensory, prefrontal cortex).
- Examined naive rats at three distinct developmental ages: 1, 6, and 12 months.
- Utilized immunohistochemistry to identify and count PV-expressing cells.
Main Results:
- A significant decrease in hippocampal PV+ cell number was observed with increasing age, showing regional and septotemporal variations.
- This age-related decrease in PV+ cells was specific to the hippocampus.
- A modest increase in PV+ cell number was noted in the prefrontal (anterior cingulate) cortex, suggesting delayed maturation.
Conclusions:
- Hippocampal PV+ cell counts decline significantly during development in rats.
- These findings underscore the importance of considering developmental changes in PV+ cells when modeling neuropathological disorders like schizophrenia and autism.
- Further research is needed to elucidate the role of PV and local circuit development in neuropathology.
Abstract:
Local circuit GABAergic neurons, including parvalbumin (PV)-containing basket cells, likely play a key role in the development, physiology, and pathology of neocortical circuits. Regionally selective and well-defined decreases in PV have been described in human postmortem schizophrenic brain tissue in both the hippocampus and prefrontal cortex. Animal models of schizophreniform dysfunction following acute and/or chronic ketamine treatment have also demonstrated decreases in PV expression. Conflicting reports with respect to PV immunoreactivity following acute and chronic ketamine treatments in rodents question the utility of using PV as a biological marker of pathology-related dysfunction. The current literature lacks sufficient and systematic characterization of normative PV expression in pharmacologically and behaviorally naïve rodent tissue. In order to understand developmental changes in PV and its putative role in neuropathology, we examined the baseline distribution of the number of cells expressing this protein at distinct developmental ages. The present study examined PV cell counts across the septotemporal axis of the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus, as well as within the retrosplenial, somatosensory, and prefrontal cortices, in 1-, 6-, and 12-month-old naïve rats. Our findings suggest that the hippocampal PV+ cell number significantly decreases as a function of age with considerable regional (CA1, CA3, and DG) and septotemporal variation, a finding that was specific to the hippocampus. Additionally, we observed a modest increase in PV cell number within the prefrontal (anterior cingulate) cortex, which is in line with findings indicating a delayed developmental maturation of this region. The present work highlights decreases in PV+ cell counts within the hippocampus across development, and points to the need for a greater understanding of the role of PV and local circuit developmental changes, as well as consideration of their development when modeling developmentally related neuropathological disorders (e.g. schizophrenia, autism).

