Subdivision-Specific Responses of Neurons in the Nucleus of the Tractus Solitarius to Activation of Mu-Opioid Receptors in the Rat

Abstract

Microinjection of opioid receptor agonists into the nucleus tractus solitarius (NTS) has differential effects on cardiovascular, respiratory, and gastrointestinal responses. This can be achieved either by presynaptic modulation of inputs onto neurons or by postsynaptic activation of receptors on neurons in specific regions. Therefore we sought to determine whether responses of neurons to activation of opioid receptors were dependent on their location within the NTS. Using whole cell patch-clamp recordings from neurons within the NTS, the mu opioid receptor (MOR) agonist [D-Ala 2 , N-Me-Phe 4 ,Gly 5 -ol]-enkephalin (DAMGO, 100 nM) hyperpolarized a proportion of neurons in the medial, dorsomedial and dorsolateral NTS, whereas no postsynaptic responses were observed in remaining subdivisions. DAMGO reduced the amplitude of solitary tract-evoked excitatory postsynaptic potentials (EPSPs) in all neurons tested, regardless of subdivision. The kappa opioid receptor (KOR) agonist U69593 (10 -20 M) also hyperpolarized a small fraction of neurons (6/79) and decreased the amplitude of EPSPs in 50% of neurons. In contrast, the delta-opioid receptor agonist DPDPE (1-4 M) had no presynaptic or postsynaptic effects on NTS neurons even after preincubation with bradykinin. Anatomical data at the light and electron microscopic level complemented electrophysiological observations with respect to MOR location and further showed that MORs were present at both presynaptic and postsynaptic sites in the dorsolateral NTS, often at the same synapse. These data demonstrate site specific responses of neurons to activation of MORs and KORs, which may underlie their ability to modulate different autonomic reflexes.

Tonic GABAA receptor conductance in medial subnucleus of the tractus solitarius neurons is inhibited by activation of μ-opioid receptors

“…However, in the present study, suppression of tonic as well as phasic GABA signaling was observed. Smith and colleagues did report an outward current with superfusion of EM-1 that they attributed to direct hyperpolarization of GABA neurons (Glatzer et al 2007), which was consistent with an earlier study (Poole et al 2007). Both studies attribute this direct hyperpolarization to the activation of postsynaptic K ϩ channels, but neither study performed additional experiments to characterize this current.…”

Pharmacology of Opioid Drugs

“…In the NTS, m-receptors are notably located on the endings of afferent neurons from the respiratory tract and peripheral sensory receptors regulating respiration, where they inhibit activity particularly of the dorsolateral and medial regions of the nucleus [127]. Respiratory rhythm generation is coordinated by interactions between the brainstem respiratory centers in the retrotrapezoid and parafacial neuron complexes and the nearby pre-Bötzinger complex (a neuronal complex identified in rodents, but not yet characterized in man).…”

Opioid Receptors on Bulbospinal Respiratory Neurons Are Not Activated During Neuronal Depression by Clinically Relevant Opioid Concentrations

“…High densities of endomorphin (endogenous opioid agonist) immunoreactive fibers and cell bodies have been found in the dorsal medial portion of the caudal NTS, a region where second-order neurons of the carotid body chemoreceptors are located . Anatomical data at the light and electron microscopic level and electrophysiological observations showed that opioid receptors are present at both pre-and postsynaptic sites in the dorsolateral NTS, often at the same synapse (Poole et al 2007). Thus it is possible that opioids affect the peripheral chemoreflex pathway by depressing synaptic input to the second-order neurons.…”