Membrane and Synaptic Actions of Halothane on Rat Hippocampal Pyramidal Neurons and Inhibitory Interneurons

Abstract

A relatively small number of inhibitory interneurons can control the excitability and synchronization of large numbers of pyramidal neurons in hippocampus and other cortical regions. Thus, anesthetic modulation of interneurons could play an important role during anesthesia. The aim of this study was to investigate effects of a general anesthetic, halothane, on membrane and synaptic properties of rat hippocampal interneurons. GABA receptor-mediated IPSCs were recorded with whole-cell patch-clamp techniques in visually identified CA1 pyramidal cells and interneurons located at the border of stratum lacunosum-moleculare and stratum radiatum. Halothane (0.35 mm congruent with 1.2 vol%) depressed evoked IPSC amplitudes recorded from both pyramidal cells and inhibitory interneurons. Also, halothane considerably prolonged the decay time constant of evoked IPSCs in pyramidal cells and interneurons. The frequencies of miniature IPSCs were increased by halothane (two- to threefold) in both types of neuron. On the other hand, halothane effects on resting membrane potentials were variable but minimal in both types of neurons. In current-clamp recordings, halothane depressed EPSP amplitudes and increased IPSP amplitudes recorded from both types of neurons. In addition, halothane increased the failure rate of synaptically evoked action potentials. Taken together, these data provide evidence that halothane increases GABA(A) receptor-mediated synaptic inhibition between synaptically connected interneurons and depresses excitatory transmission, similar to effects observed in pyramidal neurons.

Pre‐ and postsynaptic volatile anaesthetic actions on glycinergic transmission to spinal cord motor neurons

“…However, volatile anaesthetics did not increase amplitudes of either spontaneous or glycine-evoked currents. Others have reported that ethanol and volatile anaesthetics increase spontaneous inhibitory transmitter release (Banks & Pearce, 1999;Cheng et al, 1999;Mody et al, 1991;Nishikawa & MacIver, 2000;. However, other studies at supraspinal CNS sites report that volatile anaesthetics do not increase GABA A release (Antkowiak & Heck, 1997) but do inhibit glutamate release from excitatory synapses (Kirson et al, 1998).…”

“…In hippocampal pyramidal cells halothane prolongs spontaneous inhibitory postsynaptic currents (Gage & Hamill, 1981;Mody et al, 1991); volatile anaesthetics exert dual blocking and prolonging actions on postsynaptic GABA A receptors in hippocampus (Banks & Pearce, 1999). Also in hippocampus volatile anaesthetics increase miniature IPSC frequencies but depress both spontaneous and evoked IPSC amplitudes (Nishikawa & MacIver, 2000;.…”

Cellular Actions of Urethane on Rat Visual Cortical Neurons In Vitro

“…Unlike other general anesthetics that depress neuronal responses primarily through synaptic mechanisms (Franks and Lieb 1994;Nicoll et al 1975;Nishikawa and MacIver 2000;Pittson et al 2004), urethane produced little effect on the time course or amplitude of synaptically evoked inhibitory responses in olfactory cortex (Scholfield 1980)-in the only previous study to address urethane effects on synaptic transmission. Basic cellular properties such as resting membrane potential, action potential amplitude, and membrane capacitance also did not vary significantly between measures in vitro and those made in vivo from urethane-anesthetized rats (Bindman et al 1988).…”

Major Role For Tonic GABAA Conductances in Anesthetic Suppression of Intrinsic Neuronal Excitability

“…Brain slice preparation methods have previously been described in detail (Nishikawa and MacIver 2000). In short, standard transverse hippocampal slices (400 -500 m) from mature Sprague-Dawley rats (P28 -P40, most P33-36) were prepared using a vibratome.…”

“…Standard visualized slice procedures were used (Nishikawa and MacIver 2000). All interneuron recordings were from nonpyramidal CA1 neurons at or near the border of stratum radiatum and s. lacunosum-moleculare; "giant" neurons (Gulyas et al 1998) were avoided.…”