12606677

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2

To understand the role of N-methyl-d-aspartate (NMDA) receptors in the prefrontal cortex (PFC) and to investigate how the psychotomimetic drug phencyclidine (PCP) may alter PFC function, we made whole-cell recordings from PFC neurons in rat brain slices. Our result showed that most deep layer pyramidal neurons in the PFC were regular spiking cells. They could fire repetitive bursts, however, when activated by glutamate focally applied to the apical dendrite. Application of NMDA to the same dendritic spot also induced bursting, whereas application of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) evoked single spikes only. Coapplication of AMPA with NMDA evoked more single spikes and decreased NMDA-induced bursting. Experiments with NMDA and AMPA antagonists further showed that dendritic glutamate (dGlu)-induced bursting required NMDA receptor activation and was enhanced when AMPA receptors were blocked. At subanesthetic concentrations, PCP decreased dGlu-induced bursting and altered the temporal characteristics of the bursts by decreasing spikes per burst and increasing interspike intervals within bursts. The latter two changes were not observed when AMPA receptors were blocked, suggesting that they are secondary to the increased AMPA receptor contribution to glutamate responses evoked in the presence of PCP. These results suggest that NMDA receptors are essential for PFC pyramidal cells to fire in bursts in response to dGlu input and that PCP suppresses dGlu-induced bursting. Since bursting is necessary for pyramidal cells to activate GABA interneurons, the suppression effect of PCP may further lead to a weakening of the connections from pyramidal cells and GABA interneurons, thereby contributing to PCP's psychotomimetic effects.

eng

IM

MEDLINE

0022-3565

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680-7

pubmed-meshheading:12606677-Animals, pubmed-meshheading:12606677-Dendrites, pubmed-meshheading:12606677-Electrophysiology, pubmed-meshheading:12606677-Excitatory Amino Acid Agonists, pubmed-meshheading:12606677-Excitatory Amino Acid Antagonists, pubmed-meshheading:12606677-Glutamates, pubmed-meshheading:12606677-Hallucinogens, pubmed-meshheading:12606677-Ketamine, pubmed-meshheading:12606677-Lysine, pubmed-meshheading:12606677-Male, pubmed-meshheading:12606677-Membrane Potentials, pubmed-meshheading:12606677-N-Methylaspartate, pubmed-meshheading:12606677-Phencyclidine, pubmed-meshheading:12606677-Prefrontal Cortex, pubmed-meshheading:12606677-Pyramidal Cells, pubmed-meshheading:12606677-Rats, pubmed-meshheading:12606677-Rats, Sprague-Dawley, pubmed-meshheading:12606677-Receptors, AMPA, pubmed-meshheading:12606677-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:12606677-Synapses, pubmed-meshheading:12606677-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

Dendritic glutamate-induced bursting in the prefrontal cortex: further characterization and effects of phencyclidine.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't