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Schizophr Res. 2014 Aug;157(1-3):238-43. doi: 10.1016/j.schres.2014.05.005. Epub 2014 Jun 2.

A fundamental role for hippocampal parvalbumin in the dopamine hyperfunction associated with schizophrenia.

Author information

1
Department of Pharmacology, Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
2
Department of Pharmacology, Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA. Electronic address: LodgeD@uthscsa.edu.

Abstract

Postmortem studies in schizophrenia patients have demonstrated robust alterations in GABAergic markers throughout the neuraxis. It has been suggested that these alterations are restricted to subpopulations of interneurons, such as those containing the calcium binding protein parvalbumin. Indeed, a reduction in parvalbumin expression is a consistent observation in human postmortem studies, as well as, in a wide and diverse variety of animal models. However, it still remains to be determined whether this decrease in parvalbumin expression contributes to, or is a consequence of the disease. Here we utilize lentiviral delivered shRNA and demonstrate that a selective reduction in parvalbumin mRNA expression induces hyperactivity within the ventral hippocampus. In addition, we observe downstream increases in dopamine neuron population activity without changes in average firing rate or percent burst firing. These changes in dopamine neuron activity were associated with an enhanced locomotor response to amphetamine administration. These data therefore demonstrate that a reduction in ventral hippocampal parvalbumin expression is sufficient, in and of itself, to induce an augmented dopamine system function and behavioral hyper-responsivity to amphetamine, implicating a potential key role for parvalbumin in the pathophysiology of schizophrenia.

KEYWORDS:

Dopamine; Hippocampus; Parvalbumin; Schizophrenia

PMID:
24888524
PMCID:
PMC4099272
DOI:
10.1016/j.schres.2014.05.005
[Indexed for MEDLINE]
Free PMC Article
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