Maturation of GABAergic Synaptic Transmission From Neocortical Parvalbumin Interneurons Involves N-methyl-D-aspartate Receptor Recruitment of Cav2.1 Channels.

N-methyl-D-aspartate receptor (NMDAR) hypofunction during brain development is likely to contribute to the manifestation of schizophrenia (SCZ) in young adulthood. The cellular targets of NMDAR hypofunction appear to be at least in part corticolimbic fast-spiking (FS) interneurons. However, functional alterations in parvalbumin (PV)-positive FS interneurons following NMDAR hypofunction are poorly understood.

Modulation of epileptiform activity by three subgroups of GABAergic interneurons in mouse somatosensory cortex.

4-Aminopyridine (4-AP) induces ictal-like epileptiform discharges in a variety of brain regions. These events are associated with enhanced inhibitory and excitatory synaptic neurotransmission. The relative contribution of specific subclasses of GABAergic interneurons (INs) to epileptiform activity in the 4-AP model is not well characterized.

5-HT2A receptor dysregulation in a schizophrenia relevant mouse model of NMDA receptor hypofunction.

Blockade of N-methyl-D-aspartate receptors (NMDAR) is known to augment cortical serotonin 2A receptors (5-HT2ARs), which is implicated in psychosis. However, the pathways from NMDAR hypofunction to 5-HT2AR up-regulation are unclear. Here we addressed in mice whether genetic deletion of the indispensable NMDAR-subunit Grin1 principally in corticolimbic parvalbumin-positive fast-spiking interneurons, could up-regulate 5-HT2ARs leading to cortical hyper-excitability.

K 5.1-dependent CO /H -sensitive currents contribute to astrocyte heterogeneity across brain regions.

Astrocyte heterogeneity is an emerging concept in which astrocytes within or between brain regions show variable morphological and/or gene expression profiles that presumably reflect different functional roles. Recent evidence indicates that retrotrapezoid nucleus (RTN) astrocytes sense changes in tissue CO H to regulate respiratory activity; however, mechanism(s) by which they do so remain unclear. Alterations in inward K currents represent a potential mechanism by which CO /H signals may be conveyed to neurons.

GSK3β inhibition restores cortical gamma oscillation and cognitive behavior in a mouse model of NMDA receptor hypofunction relevant to schizophrenia.

Cortical gamma oscillations are believed to be involved in mental processes which are disturbed in schizophrenia. For example, the magnitudes of sensory-evoked oscillations, as measured by auditory steady-state responses (ASSRs) at 40 Hz, are robustly diminished, whereas the baseline gamma power is enhanced in schizophrenia. Such dual gamma oscillation abnormalities are also present in a mouse model of N-methyl-D-aspartate receptor hypofunction (Ppp1r2cre/Grin1 knockout mice).