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Front Cell Neurosci. 2014 Dec 10;8:420. doi: 10.3389/fncel.2014.00420. eCollection 2014.

Role of neuropsin in parvalbumin immunoreactivity changes in hippocampal basket terminals of mice reared in various environments.

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Division of Functional Neuroscience, Nara Institute of Science and Technology Ikoma City, Nara, Japan.
Department of Anatomy 2, Ryukyu University Faculty of Medicine Ryukyu, Japan.
Department of Systems Life Engineering, Maebashi Institute of Technology Maebashi, Gunma, Japan.


In vitro approaches have suggested that neuropsin (or kallikrein 8/KLK8), which controls gamma-aminobutyric acid (GABA) neurotransmission through neuregulin-1 (NRG-1) and its receptor (ErbB4), is involved in neural plasticity (Tamura et al., 2012, 2013). In the present study, we examined whether parvalbumin (PV)-positive neuronal networks, the majority of which are ErbB4-positive GABAergic interneurons, are controlled by neuropsin in tranquil and stimulated voluntarily behaving mice. Parvalbumin-immunoreactive fibers surrounding hippocampal pyramidal and granular neurons in mice reared in their home cage were decreased in neuropsin-deficient mice, suggesting that neuropsin controls PV immunoreactivity. One- or two-week exposures of wild mice to novel environments, in which they could behave freely and run voluntarily in a wheel resulted in a marked upregulation of both neuropsin mRNA and protein in the hippocampus. To elucidate the functional relevance of the increase in neuropsin during exposure to a rich environment, the intensities of PV-immunoreactive fibers were compared between neuropsin-deficient and wild-type (WT) mice under environmental stimuli. When mice were transferred into novel cages (large cages with toys), the intensity of PV-immunoreactive fibers increased in WT mice and neuropsin-deficient mice. Therefore, behavioral stimuli control a neuropsin-independent form of PV immunoreactivity. However, the neuropsin-dependent part of the change in PV-immunoreactive fibers may occur in the stimulated hippocampus because increased levels of neuropsin continued during these enriched conditions.


ErbB4; GABA; KLK8; hippocampus; interneuron; neuregulin1; synaptic plasticity

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