A-type potassium channels differentially tune afferent pathways from rat solitary tract nucleus to caudal ventrolateral medulla or paraventricular hypothalamus.

The solitary tract nucleus (NTS) conveys visceral information to diverse central networks involved in homeostatic regulation. Although afferent information content arriving at various CNS sites varies substantially, little is known about the contribution of processing within the NTS to these differences. Using retrograde dyes to identify specific NTS projection neurons, we recently reported that solitary tract (ST) afferents directly contact NTS neurons projecting to caudal ventrolateral medulla (CVLM) but largely only indirectly contact neurons projecting to the hypothalamic paraventricular nucleus (PVN). Since intrinsic properties impact information transmission, here we evaluated potassium channel expression and somatodendritic morphology of projection neurons and their relation to afferent information output directed to PVN or CVLM pathways. In slices, tracer-identified projection neurons were classified as directly or indirectly (polysynaptically) coupled to ST afferents by EPSC latency characteristics (directly coupled, jitter < 200 micros). In each neuron, voltage-dependent potassium currents (IK) were evaluated and, in representative neurons, biocytin-filled structures were quantified. Both CVLM- and PVN-projecting neurons had similar, tetraethylammonium-sensitive IK. However, only PVN-projecting NTS neurons displayed large transient, 4-aminopyridine-sensitive, A-type currents (IKA). PVN-projecting neurons had larger cell bodies with more elaborate dendritic morphology than CVLM-projecting neurons. ST shocks faithfully (> 75%) triggered action potentials in CVLM-projecting neurons but spike output was uniformly low (< 20%) in PVN-projecting neurons. Pre-conditioning hyperpolarization removed IKA inactivation and attenuated ST-evoked spike generation along PVN but not CVLM pathways. Thus, multiple differences in structure, organization, synaptic transmission and ion channel expression tune the overall fidelity of afferent signals that reach these destinations.

Differentiation of autonomic reflex control begins with cellular mechanisms at the first synapse within the nucleus tractus solitarius.

Visceral afferents send information via cranial nerves to the nucleus tractus solitarius (NTS). The NTS is the initial step of information processing that culminates in homeostatic reflex responses. Recent evidence suggests that strong afferent synaptic responses in the NTS are most often modulated by depression and this forms a basic principle of central integration of these autonomic pathways. The visceral afferent synapse is uncommonly powerful at the NTS with large unitary response amplitudes and depression rather than facilitation at moderate to high frequencies of activation. Substantial signal depression occurs through multiple mechanisms at this very first brainstem synapse onto second order NTS neurons. This review highlights new approaches to the study of these basic processes featuring patch clamp recordings in NTS brain slices and optical techniques with fluorescent tracers. The vanilloid receptor agonist, capsaicin, distinguishes two classes of second order neurons (capsaicin sensitive or capsaicin resistant) that appear to reflect unmyelinated and myelinated afferent pathways. The differences in cellular properties of these two classes of NTS neurons indicate clear functional differentiation at both the pre- and postsynaptic portions of these first synapses. By virtue of their position at the earliest stage of these pathways, such mechanistic differences probably impart important differentiation in the performance over the entire reflex pathways.

Differentiation of autonomic reflex control begins with cellular mechanisms at the first synapse within the nucleus tractus solitarius

Visceral afferents send information via cranial nerves to the nucleus tractus solitarius (NTS). The NTS is the initial step of information processing that culminates in homeostatic reflex responses. Recent evidence suggests that strong afferent synaptic responses in the NTS are most often modulated by depression and this forms a basic principle of central integration of these autonomic pathways. The visceral afferent synapse is uncommonly powerful at the NTS with large unitary response amplitudes and depression rather than facilitation at moderate to high frequencies of activation. Substantial signal depression occurs through multiple mechanisms at this very first brainstem synapse onto second order NTS neurons. This review highlights new approaches to the study of these basic processes featuring patch clamp recordings in NTS brain slices and optical techniques with fluorescent tracers. The vanilloid receptor agonist, capsaicin, distinguishes two classes of second order neurons (capsaicin sensitive or capsaicin resistant) that appear to reflect unmyelinated and myelinated afferent pathways. The differences in cellular properties of these two classes of NTS neurons indicate clear functional differentiation at both the pre- and postsynaptic portions of these first synapses. By virtue of their position at the earliest stage of these pathways, such mechanistic differences probably impart important differentiation in the performance over the entire reflex pathways.

Cellular mechanisms of baroreceptor integration at the nucleus tractus solitarius.

The autonomic nervous system makes important contributions to the homeostatic regulation of the heart and blood vessels through arterial baroreflexes, and yet our understanding of the central nervous system mechanisms is limited. The sensory synapse of baroreceptors in the nucleus tractus solitarius (NTS) is unique because its participation is obligatory in the baroreflex. Here we describe experiments targeting this synapse to provide greater understanding of the cellular mechanisms at the earliest stages of the baroreflex. Our approach utilizes electrophysiology, pharmacology, and anatomical tracers to identify and evaluate key elements of the sensory information processing in NTS.

Chemical stimulation of the dorsomedial hypothalamus elevates plasma ACTH in conscious rats.

The hallmark neuroendocrine response to stress is increased plasma ACTH. Inhibition of neurons in the region of the dorsomedial hypothalamus (DMH) attenuates experimental air stress-induced elevation of heart rate (HR), mean arterial pressure (MAP), and plasma ACTH. We hypothesized that, under basal conditions, stimulation of the DMH would mimic the neuroendocrine and cardiovascular response to air stress. We examined the effects of unilateral microinjection (100-nl vol) of bicuculline methiodide (BMI, 10 pmol), kainate (KA, 1 or 3 pmol), and N-methyl-D-aspartate (5 pmol) into the DMH or the paraventicular nucleus (PVN) on HR, MAP, locomotor activity, and plasma ACTH in conscious rats. Chemical stimulation of the DMH with KA or BMI produced increased locomotor activity and effects on HR, MAP, and plasma ACTH that together mimicked the pattern seen in experimental stress. Similar treatment in the PVN produced only small increases in MAP. Thus activation of neurons in the region of the DMH results in increased secretion of ACTH along with other changes typically seen in experimental stress.

Isoprostanes, novel eicosanoids that produce nociception and sensitize rat sensory neurons.

Isoprostanes are a novel class of eicosanoids primarily formed by peroxidation of arachidonic acid. Because of their potential as inflammatory and/or hyperalgesic agents whose formation is largely independent of cyclooxygenases, we examined whether 8-iso prostaglandin E(2) (8-iso PGE(2)) or 8-iso prostaglandin F(2alpha) (8-iso PGF(2alpha)) reduces mechanical and thermal withdrawal threshold in rats, and whether they sensitize rat sensory neurons. Injection of 1 microg of 8-iso PGE(2) (in 2.5 microl) into the hindpaw of rats significantly reduced mechanical and thermal withdrawal thresholds, whereas 1 microg of 8-iso PGF(2alpha) elicited a transient decrease in only the mechanical withdrawal threshold. Both isoprostanes enhanced the firing of C-nociceptors in a concentration-dependent manner when injected into peripheral receptive fields. Exposing sensory neurons grown in culture to 1 microM 8-iso PGE(2) or 8-iso PGF(2alpha) augmented the number of action potentials elicited by a ramp of depolarizing current. In contrast, 8-iso PGE(2) but not 8-iso PGF(2alpha) enhanced the release of substance P- and calcitonin gene-related peptide-like immunoreactivity from isolated sensory neurons. Ten micromolar 8-iso PGE(2) stimulated peptide release directly, whereas treatment with 1 microM 8-iso PGE(2) augmented the release evoked by either bradykinin or capsaicin. Pretreating neuronal cultures with the nonsteroidal anti-inflammatory drug ketorolac did not alter the sensitizing action of 8-iso PGE(2) on peptide release, suggesting that this action of the isoprostane was not secondary to the production of prostaglandins via the cyclooxygenase pathway. These data support the notion that isoprostanes are an important class of inflammatory mediators that augment nociception.