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

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.

Area-specific resonance of excitatory networks in neocortex: control by outward currents.

During disinhibition or low [Mg++](o) buffer, 7-14 Hz ( approximately 10 Hz) oscillations are generated by excitatory networks of interconnected pyramidal cells in motor (agranular) cortex but are absent in barrel (granular) cortex. Here we studied if the inability of barrel cortex to produce approximately 10 Hz oscillations during these conditions is because barrel cortex networks lack the necessary cellular mechanisms or, alternatively, because those mechanisms are inhibited by outward currents. The results show that blockers of slowly inactivating voltage-dependent K+ currents unmask approximately 10 Hz oscillations in barrel cortex, and this occurs in unison with the unmasking of intrinsic inward Ca++ currents that are kept suppressed by the outward currents. Moreover, the approximately 10 Hz oscillations unmasked in barrel cortex occur independently in upper and lower layers indicating that the approximately 10 Hz oscillation mechanisms are kept suppressed in multiple networks. The results reveal that the propensity of distinct excitatory networks of neocortex to generate epileptiform oscillatory activities is controlled by outward currents.

Resonance (approximately 10 Hz) of excitatory networks in motor cortex: effects of voltage-dependent ion channel blockers.

The motor cortex generates synchronous network oscillations at frequencies between 7 and 14 Hz during disinhibition or low [Mg2+]o buffers, but the underlying mechanisms are poorly understood. These oscillations, termed here approximately 10 Hz oscillations, are generated by a purely excitatory network of interconnected pyramidal cells because they are robust in the absence of GABAergic transmission. It is likely that specific voltage-dependent currents expressed in those cells contribute to the generation of approximately 10 Hz oscillations. We tested the effects of different drugs known to suppress certain voltage-dependent currents. The results revealed that drugs that suppress the low-threshold calcium current and the hyperpolarization-activated cation current are not critically involved in the generation of approximately 10 Hz oscillations. Interestingly, drugs known to suppress the persistent sodium current abolished approximately 10 Hz oscillations. Furthermore, blockers of K+ channels had significant effects on the oscillations. In particular, blockers of the M-current abolished the oscillations. Also, blockers of both non-inactivating and slowly inactivating voltage-dependent K+ currents abolished approximately 10 Hz oscillations. The results indicate that specific voltage-dependent non-inactivating K+ currents, such as the M-current, and persistent sodium currents are critically involved in generating approximately 10 Hz oscillations of excitatory motor cortex networks.