An atlas of the rat subpostremal nucleus tractus solitarius.

The nucleus tractus solitarius (NTS) in the dorsal medulla is the principal visceral sensory relay nucleus in the brain. In the rat, numerous lines of evidence indicate that the caudal NTS at the level of the area postrema serves as a major integrating site for coordinating cardiorespiratory reflexes and viscerobehavioral responses. This region of the caudal NTS not only exhibits high densities of binding sites for an impressive array of transmitters and modulators but microinjections of many of these same neuroactive substances into the rat subpostremal NTS elicit pronounced cardiorespiratory and visceral response patterns. This report provides an abbreviated atlas of the rat subpostremal NTS consisting of a series of transverse, sagittal, and horizontal plates. Photomicrographs, together with their corresponding schematic drawings, are provided for the serial sections generated from each reference plane.

Adenosine receptor subtypes in the brainstem mediate distinct cardiovascular response patterns.

A limited occipital craniotomy was conducted on urethane-chloralose anesthetized, spontaneously breathing rats to expose the caudal medulla in the region of the obex. Microinjections of highly selective agonists for adenosine receptor subtypes were made into the medial region of the caudal nucleus tractus solitarius (NTS) at the level of the posterior portion of the area postrema. Cardiorespiratory parameters were subsequently recorded for a 60-min test period following microinjection of drug or vehicle solutions. The following selective adenosine receptor agonists were used: the A1 agonist, N6-cyclopentyladenosine (CPA), which is 480-fold selective for A1 receptors in rat brain binding assays, and the A2 agonist, 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680), which is 170-fold selective for A2 receptors in rat brain binding studies and over 1500-fold selective in functional assays. The results showed that distinct and converse cardiovascular response patterns were elicited by these selective agonists for adenosine receptor subtypes following microinjections into the caudal NTS. Specifically, CGS 21680 selectively elicited potent dose-related decreases in mean arterial blood pressure (ED50 = 0.064 nmol/kg) and dose-related decreases in pulse pressure (ED50= 0.058 nmol/kg). Conversely, CPA selectively elicited potent dose-related increases in mean arterial blood pressure (ED50 = 0.62 nmol/kg) and dose-related increases in pulse pressure (ED50 = 0.70 nmol/kg). Additionally, the overall agonist-mediated response patterns were dramatically different wherein the CGS agonist exhibited a considerably more rapid time course in eliciting its hypotensive responses whereas CPA exhibited a more delayed and substantially longer time course to exert its hypertensive responses. Additionally, these distinct and converse cardiovascular response patterns were further shown to be receptor-selective since the depressor responses elicited by the A2 receptor agonist, CGS 21680, and the pressor responses elicited by the A1 receptor agonist, CPA, were completely and selectively blocked, respectively, by the selective A2 receptor antagonist, CGS 15943A, and the selective A1 receptor antagonist, DPCPX. Taken together, these findings provide persuasive in vivo evidence showing that pharmacologic activation of adenosine receptor subtypes in the caudal NTS of rats elicits specific response patterns with selective and opposite actions on cardiorespiratory behavior. These data also indicate that separate physiologic responses are specifically mediated by A2 receptors in the intact nervous system and thereby lend additional support to the case for using in vivo models to assess the functional role of adenosine A2 receptors in brain function.

The adenosine analog, 5'-N-ethylcarboxamidoadenosine, exerts mixed agonist action on cardiorespiratory parameters in the intact but not decerebrate rat following microinjections into the nucleus tractus solitarius.

A limited occipital craniotomy was conducted on intact and decerebrate urethane-anesthetized, spontaneously breathing rats to expose the caudal medulla in the region of the obex. Microinjections of 5'-N-ethylcarboxamidoadenosine (NECA), a metabolically stable adenosine analog which exhibits mixed agonist properties for adenosine receptor subtypes, were made into the medial region of the caudal nucleus tractus solitarius (NTS) at the level of the caudal tip of the area postrema, an area of the NTS in which there is known to be a functional co-existence of cardiovascular and respiratory-related neuronal elements. Cardiorespiratory responses were subsequently recorded for a 30-min test period. In the intact rat, microinjections of NECA produced significant dose-related reductions in respiratory rate which were accompanied by dose-dependent increases in tidal volume and these pronounced effects on respiration persisted throughout the test period. On the other hand, microinjections of NECA into this region of the NTS of the intact rat elicited complex, bi-directional cardiovascular responses, producing hypotension (at lower doses) and pressor responses (at higher doses) in addition to bradycardia (at lower doses). In an effort to examine the functional interactions between the NTS and forebrain structures involved in cardiorespiratory control, microinjections of NECA in the identical dose range were made into the same NTS sites of a separate group of urethane-anesthetized, spontaneously breathing rats in which reciprocal connections between forebrain areas and the brainstem had been disrupted by acute supracollicular decerebration. A simulating electrode, placed in the paraventricular nucleus of the hypothalamus (PVH), was used to confirm complete transection during the experiment and to ascertain the integrity of reciprocal connections between the brainstem and rostral brain regions involved in cardiorespiratory control. Although decerebration at the supracollicular level negligibly affected basal cardiorespiratory parameters, microinjections of NECA into the NTS revealed dramatic differences in the cardiovascular response patterns between intact and decerebrate rats. Whereas cardiovascular responses elicited by microinjections into the NTS were significantly affected by supracollicular decerebration, respiratory responses were highly similar for both intact and decerebrate animals. Indeed, repeated measures MANOVA indicated that there were no significant differences in the time-related or dose-related responses in the depression of respiration between decerebrate and intact rats following NECA microinjections.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiorespiratory response patterns elicited by microinjections of neuropeptide Y in the nucleus tractus solitarius.

A limited occipital craniotomy was conducted on anesthetized, spontaneously breathing rats to expose the caudal medulla in the region of the obex. Microinjections of neuropeptide Y (NPY), a putative neuromodulator associated with catecholaminergic (CA) synapses, were made into the medial region of the caudal nucleus tractus solitarius (NTS) at the level of the posterior portion of the area postrema, an area of the NTS in which there is known to be a functional coexistence of cardiovascular and respiratory-related neuronal elements. This region of the caudal NTS in the rat is not only the principal site of termination of baro- and chemoreceptor afferents, but it also has profuse reciprocal connections with NPY-containing cardiorespiratory control regions in the hypothalamus and with other brainstem regulatory nuclei. Moreover, this same region of the rat NTS also shows very high densities of NPY binding sites. Cardiorespiratory responses were subsequently recorded for a 60-min test period following NPY administration. Microinjections of NPY, in the dose range of 10-100 pmol/rat, into the caudal NTS of intact rats produced significant dose-related reductions in mean arterial blood pressure, pulse pressure and minute volume. To a lesser extent, NPY microinjections also produced significant reductions in heart rate, respiratory rate and tidal volume. In a series of separate experiments, in an effort to ascertain the modulatory influences of rostral brain regions on these NPY-evoked, NTS-mediated cardiorespiratory response patterns, microinjections of NPY were made under identical anesthetic and experimental conditions in a group of rats wherein reciprocal connections between the NTS and rostral brain regions had been disrupted via supracollicular decerebration. In addition, since NPY microinjections were made into specific loci wherein afferent inputs from cardiopulmonary receptors are known to converge in the rat NTS, the effects of bilateral vagotomy on NPY-evoked, NTS-mediated cardiorespiratory response patterns were also examined in otherwise intact rats and under the same experimental conditions. The effects of NPY microinjections at the same dosage on NTS-mediated cardiorespiratory response patterns were subsequently compared among the intact, decerebrate and vagotomized rats. The results showed that whereas the hypotensive actions of NPY were not affected by decerebration, vagotomy significantly increased the magnitude of the hypotension elicited by NPY microinjections in comparison to the intact and decerebrate groups of rats. On the other hand, vagotomy abolished the NPY-evoked bradycardia which had a similar magnitude in both intact and decerebrate rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiorespiratory responses following electrical stimulation of caudal sites in the rat medulla.

A limited occipital craniotomy was conducted on urethane-anesthetized rats to expose the caudal medulla in the region of the obex. Discrete bipolar electrical stimulation was administered at sites in the dorsal medulla of spontaneously breathing rats in the vicinity of the caudal nucleus tractus solitarius (NTS) and adjacent reticular formation. Cardiorespiratory responses were recorded during microstimulation at three separate stimulating frequencies to examine the functional interaction of cardiovascular and respiratory-related neuronal elements in the NTS. Microstimulation was conducted at sites in the dorsal and medial regions of the NTS beginning at the level of the area postrema and extending posteriorly through the rostrocaudal course of the NTS; microstimulation was also conducted at midline sites in the commissural region of the NTS and the ventral and ventrolateral regions of the caudal NTS. Microstimulation of loci in the reticular formation adjacent to these NTS sites did not elicit any cardiorespiratory responses whereas stimulation of individual NTS regions elicited specific patterns of cardiorespiratory responses. Specifically, microstimulation of the dorsal and medial NTS at the level of the area postrema elicited pressor responses associated with apneic/hypopneic responses whereas stimulation of midline sites in the commissural region, dorsomedial sites caudal to the area postrema and the ventral and ventrolateral areas of the caudal regions of the NTS elicited depressor responses associated with bradycardic and apneic/hypopneic responses. The most profound respiratory effects (i.e., apnea) and heart rate responses (i.e., bradycardia) were seen following stimulation of the ventral and ventrolateral regions of the caudal NTS. These findings support the notion that the caudal NTS is a major site for coordinating cardiorespiratory afferent information in the rat and it is also apparent from this study that specific regions of the caudal NTS demonstrate a functional coexistence of cardiovascular and respiratory-related neurons. Finally, the results from this study showing the regional specificity and frequency-dependent characteristics of cardiorespiratory response patterns elicited by microstimulation suggest that the local microcircuitry and intrinsic neuronal networks in the more caudal regions of the rat NTS are more complex and heterogeneous than hitherto revealed.