LIMBIC GAMMA-RHYTHMS - I - PHASE-LOCKED OSCILLATIONS IN HIPPOCAMPAL CA1 AND SUBICULUM

Gamma oscillations (similar to 40 Hz) were induced in transverse hippo campal slices by tetanic stimulation of CA1 and/or subiculum. Tetanic stimulation of each site elicited population gamma oscillations in the surrounding tissue <400 mu m away. Stimulation of CA1 alone could evo ke activity at both CA1 and subiculum. Subicular stimulation, however, did not transmit to CA1. When the rostral end of CAI was stimulated, gamma oscillations transmitted across <1.5 mm of silent CA1 before rea ppearing in the subiculum. Tetanic stimulation of CA1 increased [K+](o ), to 8.2 +/- 1.5 mM (mean +/- SE). The location of the peak increase corresponded to the site of local gamma generation. Silent areas of CA 1 experienced smaller [K+](o) increases, to 4.9 +/- 0.7 mM. The subicu lum, which generated gamma, remained at the baseline 3.0 mM. Although fluctuations in [K+](o) may have an impact on the generation of gamma rhythms, they are not necessary for them. Gamma oscillations had simil ar frequencies in CA1 and subiculum (40.4 +/- 2.9 and 43.9 +/- 3.1 Hz, respectively). When present in both, the oscillations typically were phase locked with the subiculum lagging by 5.4 +/- 1.8 ms. When both C A1 and subiculum were stimulated the lag decreased by 28%. These delay s approximate those expected for the conduction velocity of axone betw een the two regions, here estimated at 0.52 +/- 0.07 m/s. Transmission of gamma oscillations from CA1 to subiculum was blocked by the focal addition of the lpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic aci d-receptor antagonist, 6-nitro-7-sulfamoylbenzo [f] quinoxaline-2,3-di one, to the subiculum. Oscillations induced in CA1 by local tetanic st imulation were blocked by focal application of the gamma-aminobutyric acid-A (GABA(A)) receptor antagonist, bicuculline, to CA1. Focal appli cation of bicuculline to the subiculum blocked gamma due to subicular stimulation but not that due to CA1 stimulation. Bath-applied bicucull ine disrupted subicular gamma evoked by subicular stimulation and led to a transient period of epileptiform responses before completely bloc king responses. The further addition of the GABA(B) receptor antagonis t, CGP 55845A, reversed this block, restoring the epileptic discharges evoked by tetanic stimulation. This suggests that the subiculum diffe rs from hippocampal CA3 and neocortex, in having a powerful GABA(B) re ceptor-dependent mechanism to prevent epileptic discharges. The subicu lum generates gamma rhythms both in response to local stimulation and to gamma rhythms evoked in CA1. Subicular gamma differs from that in C A1 in the presence of population spike doublets rather than singlets o n many cycles. In both areas, generation of gamma by local stimulation depends on GABA(A) receptors, suggesting that the subiculum shares th e interneuronal network mechanism we proposed for CA1.