Regional variations and substrates of high-frequency rhythmic activity indu
ced by cholinergic stimulation were studied in hippocampal slices with 64-e
lectrode 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 shi
fts 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 associa
ted with basal sources, lasting similar to 10 msec, followed by apical sour
ces and basal sinks, lasting similar to 20 msec, in a repeating pattern wit
h a period in the range of 15-25 Hz. (4) Carbachol-induced beta waves in th
e hippocampus were accompanied by 40 Hz (gamma) oscillations in deep layers
of the entorhinal cortex. (5) Cholinergically elicited beta and gamma rhyt
hms were eliminated by antagonists of either AMPA or GABA receptors. Benzod
iazepines markedly enhanced beta activity and sometimes introduced a distin
ct gamma frequency peak. (6) Twenty Hertz activity after orthodromic activa
tion of field CA3 was distributed in the same manner as carbachol-induced b
eta 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 in
dependently in hippocampal subfields from oscillatory circuits involving (1
) bursts of pyramidal cell discharges, (2) activation of a subset of feedba
ck interneurons that project apically, and (3) production of a GABA(A)-medi
ated hyperpolarization in the outer portions of the apical dendrites of pyr
amidal neurons.