alpha-Chloralose diminishes gamma oscillations in rat hippocampal slices

Abstract

alpha-Chloralose is an anesthetic characterized by its ability to maintain animals in physiological conditions though immobilized and anesthetized. In addition, alpha-chloralose induces a loss of consciousness with little influence on either pain response or cardiovascular reflexes. The pharmacological mechanisms of alpha-chloralose's actions are poorly understood. In vitro experiments have demonstrated alpha-chloralose enhances GABA(A) receptor function, which may underlie its anesthetic effect. However, how alpha-chloralose affects hippocampal synaptic function and neuronal network synchronization is unknown. In the present study, we performed electrophysiological recordings to examine the effects of alpha-chloralose on synaptic transmission, tetanic stimulation-induced gamma oscillations (30-80 Hz) and neuronal receptor function in rat hippocampal slices and dissociated hippocampal CA1 pyramidal neurons. The results demonstrated that alpha-chloralose (30-100 microM) diminished tetanic stimulation-induced gamma oscillations without affecting single stimulation-induced field potential responses. In single, dissociated hippocampal CA1 pyramidal neurons, alpha-chloralose activated GABA(A) receptors at a high concentration while it potentiated GABA(A) receptor-mediated currents at low concentrations. However, alpha-chloralose did not affect glutamate-, glycine-, or ACh-induced currents. Slice-patch recordings revealed alpha-chloralose enhanced GABAergic leak current and prolonged the decay constant of spontaneous inhibitory postsynaptic currents (sIPSCs). It is concluded that alpha-chloralose suppresses hippocampal gamma oscillations without significantly affecting basic synaptic transmission or ionotropic glutamate, choline and glycine receptor function. Enhancement of GABAergic leak current and prolongation of GABAergic sIPSCs by alpha-chloralose likely underlie its disruption of neuronal network synchronization in the hippocampus.