Origins and distribution of cholinergically induced β rhythms in hippocampal slices

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 beta 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 similar to 10 msec, followed by apical sources and basal sinks, lasting similar to 20 msec, in a repeating pattern with a period in the range of 15-25 Hz. (4) Carbachol-induced beta waves in the hippocampus were accompanied by 40 Hz (gamma) oscillations in deep layers of the entorhinal cortex. (5) Cholinergically elicited beta and gamma rhythms were eliminated by antagonists of either AMPA or GABA receptors. Benzodiazepines markedly enhanced beta activity and sometimes introduced a distinct gamma frequency peak. (6) Twenty Hertz activity after orthodromic activation of field CA3 was distributed in the same manner as carbachol-induced beta 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 beta 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.