Enhanced temporal stability of cholinergic hippocampal gamma oscillations following respiratory alkalosis in vitro

The decrease in brain CO2 partial pressure (pCO(2)) that takes place both d uring voluntary and during pathological hyperventilation is known to induce gross alterations in cortical functions that lead to subjective sensations and altered states of consciousness. The mechanisms that mediate the effec ts of the decrease in pCO(2) at the neuronal network level are largely unex plored. In the present work, the modulation of gamma oscillations by hypoca pnia was studied in rat hippocampal slices. Field potential oscillations we re induced by the cholinergic agonist carbachol under an N-methyl-D-asparta te (NMDA)-receptor blockade and were recorded in the dendritic layer of the CA3 region with parallel measurements of changes in interstitial and intra neuronal pH (pH(o) and pH(i), respectively). Hypocapnia from 5 to 1% CO2 le d to a stable monophasic increase of 0.5 and 0.2 units in pH(o) and pH(i), respectively. The mean oscillation frequency increased slightly but signifi cantly from 32 to 34 Hz and the mean gamma-band amplitude (20 to 80 Hz) dec reased by 20%. Hypocapnia induced a dramatic enhancement of the temporal st ability of the oscillations, as was indicated by a two-fold increase in the exponential decay time constant fitted to the autocorrelogram. A rise in p H(i) evoked by the weak base trimethylamine (TriMA) was associated with a s light increase in oscillation frequency (37 to 39 Hz) and a decrease in amp litude (30%). Temporal stability, on the other hand, was decreased by TriMA , which suggests that its enhancement in 1% CO2 was related to the rise in pH(o). In 1% CO2, the decay-time constant of the evoked monosynaptic pyrami dal inhibitory postsynaptic current (IPSC) was unaltered but its amplitude was enhanced. This increase in IPSC amplitude seems to significantly contri bute to the enhancement of temporal stability because the enhancement was a lmost fully reversed by a low concentration of bicuculline. These results s uggest that changes in brain pCO(2) can have a strong influence on the temp oral modulation of gamma rhythms.