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Dendritic glutamate-induced bursting in the prefrontal cortex: further characterization and effects of phencyclidine.
J Pharmacol Exp Ther. 2003 May; 305(2):680-7.JP

Abstract

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.

Authors+Show Affiliations

Department of Psychiatry, Yale University School of Medicine, 300 George Street, New Haven, CT 06511, USA. wei-xing.shi@yale.eduNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

12606677

Citation

Shi, Wei-Xing, and Xue-Xiang Zhang. "Dendritic Glutamate-induced Bursting in the Prefrontal Cortex: Further Characterization and Effects of Phencyclidine." The Journal of Pharmacology and Experimental Therapeutics, vol. 305, no. 2, 2003, pp. 680-7.
Shi WX, Zhang XX. Dendritic glutamate-induced bursting in the prefrontal cortex: further characterization and effects of phencyclidine. J Pharmacol Exp Ther. 2003;305(2):680-7.
Shi, W. X., & Zhang, X. X. (2003). Dendritic glutamate-induced bursting in the prefrontal cortex: further characterization and effects of phencyclidine. The Journal of Pharmacology and Experimental Therapeutics, 305(2), 680-7.
Shi WX, Zhang XX. Dendritic Glutamate-induced Bursting in the Prefrontal Cortex: Further Characterization and Effects of Phencyclidine. J Pharmacol Exp Ther. 2003;305(2):680-7. PubMed PMID: 12606677.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dendritic glutamate-induced bursting in the prefrontal cortex: further characterization and effects of phencyclidine. AU - Shi,Wei-Xing, AU - Zhang,Xue-Xiang, Y1 - 2003/01/24/ PY - 2003/2/28/pubmed PY - 2003/5/31/medline PY - 2003/2/28/entrez SP - 680 EP - 7 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 305 IS - 2 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/12606677/Dendritic_glutamate_induced_bursting_in_the_prefrontal_cortex:_further_characterization_and_effects_of_phencyclidine_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=12606677 DB - PRIME DP - Unbound Medicine ER -