Tamar Dugladze

The medial entorhinal cortex (mEC) plays a critical role for spatial navigation and memory. While many studies have investigated the principal neurons within the entorhinal cortex, much less is known about the inhibitory circuitries within this structure. Here, we describe for the first time in the mEC a subset of parvalbumin-positive (PV+) interneurons (INs)—stuttering cells (STUT)—with morphological, intrinsic electrophysiological, and synaptic properties distinct from fast-spiking PV+ INs. In contrast to the fast-spiking PV+ INs, the axon of the STUT INs also terminated in layer 3 and showed subthreshold membrane oscillations at gamma frequencies. Whereas the synaptic output of the STUT INs was only weakly reduced by a μ-opioid agonist, their inhibitory inputs were strongly suppressed. Given these properties, STUT are ideally suited to entrain gamma activity in the pyramidal cell population of the mEC. We propose that activation of the μ-opioid receptors decreases the GABA release from the PV+ INs onto the STUT, resulting in disinhibition of the STUT cell population and the consequent increase in network gamma power. We therefore suggest that the opioid system plays a critical role, mediated by STUT INs, in the neural signaling and oscillatory network activity within the mEC.

Schizophrenia is a common psychiatric disorder of high incidence, affecting approximately 1% of the world population. The essential neurotransmitter pathology of schizophrenia remains poorly defined, despite huge advances over the past half-century in identifying neurochemical and pathological abnormalities in the disease. The dopamine/serotonin hypothesis has originally provided much of the momentum for neurochemical research in schizophrenia. In recent years, the attention has, however, shifted to the glutamate system, the major excitatory neurotransmitter in the CNS and towards a concept of functional imbalance between excitatory and inhibitory transmission at the network level in various brain regions in schizophrenia. The evidence indicating a central role for the NMDA-receptor subtype in the aetiology of schizophrenia has led to the NMDA-hypofunction model of this disease and the use of phencyclidines as a means to induce the NMDA-hypofunction state in animal models. The purpose of this review is to discuss recent findings highlighting the importance of the NMDA-hypofunction model of schizophrenia, both from a clinical perspective, as well as in opening a line of research, which enables electrophysiological studies at the cellular and network level in vitro. In particular, changes in excitation - inhibition (E/I) balance in the NMDA-hypofunction model of the disease and the resulting changes in network behaviours, particularly in gamma frequency oscillatory activity, will be discussed.