Electrophysiological and pharmacological analysis of synaptic inputs to pulmonary rapidly adapting receptor relay neurons in the rat.

The information from pulmonary rapidly adapting stretch receptors (RARs) to the central nervous system (CNS) is relayed in the nucleus tractus solitarii (NTS). The second-order neurons in the NTS referred to as RAR cells have recently been shown to receive rhythmic inputs from the central respiratory system in addition to the main inputs from RAR afferents. The present study analyzed these synaptic inputs by intracellular recordings from RAR cells, and by extracellular recordings combined with local applications of neuroactive drugs to RAR cells, in Nembutal-anesthetized, paralyzed, and artificially ventilated rats. The intracellular analysis identified both excitatory postsynaptic potentials (EPSPs) elicited presumably by RAR afferents and inhibitory postsynaptic potentials (IPSPs) synchronous with central inspiratory activity. This inhibitory input, called I suppression, was the origin of respiratory modulation of RAR cell firing, and its time course suggested that some unidentified inspiratory neurons with an augmenting firing pattern were the source of the inhibition. The pharmacological analysis suggested the types of neurotransmitters used in these synaptic events. First, glutamate was shown to be the primary neurotransmitter at the synapse between RAR afferents and RAR cells. Iontophoretic applications of the non-NMDA glutamate antagonist, CNQX, abolished RAR cell firing almost completely in response to lung inflation and deflation and to electrical stimulation of the vagus nerve. Second, glycinergic inputs which inhibited RAR cells in the inspiratory phase were revealed by applications of the glycine antagonist, strychnine. That is, the I suppression was greatly diminished by applications of strychnine. Third, although applications of the GABA(A) receptor antagonist, bicuculline, had little effect on I suppression, bicuculline markedly increased the baseline firing of RAR cells. These results imply that the information path from RARs to the CNS is regulated at the level of RAR cells by phasically-acting glycinergic inhibition in the inspiratory phase and tonically-acting GABAergic inhibition; the results also provide new insights into the neuronal mechanisms of RAR-induced reflexes.