Mathers

Research Interests

Glycinergic and GABAergic Neurotransmission, Anesthetic and Analgesic Drug Actions, Patch Clamp ElectrophysiologyThe thalamus plays a key role in maintaining consciousness and in perception of sensory inputs, including pain. Traditionally, the major inhibitory neurotransmitter in thalamic nuclei was thought to be γ-aminobutyric acid (GABA). Our recent studies show that thalamic inhibition is much more heterogeneous than hitherto imagined. Electrical stimulation of sensory pathways evokes inhibitory synaptic responses mediated by the neurotransmitter glycine in many dorsal thalamic neurons. These glycinergic currents are themselves heterogeneous, decaying with rapid or slow time courses.

The thalamus is an important site of action for anesthetic drugs, long believed to act mainly by potentiating synaptic currents mediated by GABA. However, we have shown that the anesthetic barbiturate pentobarbital has multiple, additional actions that also inhibit cell firing, including activation of leak conductance and inhibition of inward rectifiers. Amobarbital, a chemical isomer of pentobarbital, affects only GABA responses. The anticonvulsant barbiturate phenobarbital has little effect in thalamus, but potentiates GABA currents in neocortical neurons. These results show that anesthetic action is highly structure- and brain region-dependent and that anesthesia likely involves drug actions at many membrane receptors and ion channels in the thalamus.