A Specialized Nmda Receptor Function In Layer 5 Recurrent Microcircuitry Of The Adult Rat Prefrontal Cortex

摘要

In the prefrontal cortex, NMDA receptors are important for normal prefrontal functions such as working memory, and their dysfunction plays a key role in the pathological processes of psychiatric disorders such as schizophrenia. Little is known, however, about the synaptic properties of NMDA receptors in the local circuits of recurrent excitation, a leading candidate mechanism underlying working memory. We investigated the NMDA receptor-mediated currents at monosynaptic connections between pairs of layer 5 pyramidal neurons. We found that NMDA receptor-mediated currents at prefrontal synapses in the adult, but not young, rats exhibit a twofold longer decay time-constant and temporally summate a train of stimuli more effectively, compared to those in the primary visual cortex. Experiments with pharmacological, im-munocytochemical, and biochemical approaches further suggest that, in the adult animals, neurons express significantly more NR2B subunits in the prefrontal cortex than the visual cortex. The NR2B-rich synapses in the prefrontal circuitry may be critically implicated in online cognitive computations and plasticity in learning, as well as psychiatric disorders.