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The Journal of Neuroscience, November 15, 2000, 20(22):8462-8473

Origins and Distribution of Cholinergically Induced  Rhythms in Hippocampal Slices

Ken Shimono¹, Fernando Brucher², Richard Granger², Gary Lynch³, and Makoto Taketani¹

¹ Technology Development Center, Panasonic, Cypress, California 90630, and Departments of ² Information and Computer Science and ³ Psychiatry and Human Behavior, University of California, Irvine, California 92697

Regional variations and substrates of high-frequency rhythmic activity induced by cholinergic stimulation were studied in hippocampal slices with 64-electrode recording arrays. (1) Carbachol triggered  waves (17.6 ± 5.7 Hz) in pyramidal regions of 75% of the slices. (2) The waves had phase shifts across the cell body layers and were substantially larger in the apical dendrites than in cell body layers or basal dendrites. (3) Continuous, two-dimensional current source density analyses indicated apical sinks associated with basal sources, lasting ~10 msec, followed by apical sources and basal sinks, lasting ~20 msec, in a repeating pattern with a period in the range of 15-25 Hz. (4) Carbachol-induced  waves in the hippocampus were accompanied by 40 Hz () oscillations in deep layers of the entorhinal cortex. (5) Cholinergically elicited  and  rhythms were eliminated by antagonists of either AMPA or GABA receptors. Benzodiazepines markedly enhanced  activity and sometimes introduced a distinct  frequency peak. (6) Twenty Hertz activity after orthodromic activation of field CA3 was distributed in the same manner as carbachol-induced  waves and was generated by a current source in the apical dendrites of CA3. This source was eliminated by high concentrations of GABA_A receptor blockers. It is concluded that cholinergically driven  rhythms arise independently in hippocampal subfields from oscillatory circuits involving (1) bursts of pyramidal cell discharges, (2) activation of a subset of feedback interneurons that project apically, and (3) production of a GABA_A-mediated hyperpolarization in the outer portions of the apical dendrites of pyramidal neurons.

Key words: current source density; rhythm; acetylcholine; hippocampus; multielectrode array; rhythm

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20228462-12$05.00/0

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