Sympathoexcitatory Neurons Research Articles

Chapter 10 Some properties of the sympathoinhibition from the caudal ventrolateral medulla oblongata in the cat

Publisher Summary Neurons in the caudal ventrolateral medulla oblongata (CVLM) play an important role in the control of sympathetic activity. The excitation of these neurons by small injections of excitatory amino acids causes an inhibition of sympathetic activity and a fall in arterial blood pressure. This chapter presents a study that clarifies the question that whether the sympathoinhibition from CVLM is because of post-synaptic inhibition or the disfacilitation of sympathetic preganglionic neurons (SPNs) by first studying the spinal pathway of this inhibitory response. If its pathway in the spinal cord could be dissociated from the descending pathway of sympathoexcitatory neurons in rostral ventrolateral medulla (RVLM) that runs in the dorso- and ventrolateral funiculus of the spinal cord, this would be strong evidence against the disfacilitation of SPNs. Because more direct evidence for either disfacilitation or post-synaptic inhibition should be provided by intracellular recordings of SPNs, this question has also been addressed by recording SPNs intracellularly and studying the effects of glutamate injections into CVLM on their membrane potential. It has also been studied if noradrenaline acting on α 2 -adrenergic receptors is involved as a transmitter in this inhibition and if this sympathoinhibition involves an afferent projection from the CVLM to the hypothalamus or cerebellum.

Respiratory-related activity of sympathoexcitatory neurons in the rostral ventrolateral medulla

Respiratory-related activity of sympathoexcitatory neurons in the rostral ventrolateral medulla

An enkephalin-containing pathway from nucleus tractus solitarius to the pressor area of the rostral ventrolateral medulla of the rabbit

A technique combining retrograde tracing of wheat germ-conjugated gold particles with immunocytochemical demonstration of enkephalin-containing neurons was used to study intramedullary enkephalin-containing pathways to the presser area of the rostral ventrolateral medulla in rabbits. The rostral ventrolateral medulla represents a main source of bulbospinal sympathoexcitatory neurons, and is critical to the tonic and reflex control of blood pressure. Firstly, the distribution of enkephalin-positive neurons and terminal fibres in rabbit medulla were described, with special reference to a moderately dense terminal plexus in the rostral ventrolateral medulla. Then, retrograde tracing studies were conducted; the rostral ventrolateral medullary presser region was first localized by injection of l-glutamate (25 nmol in 50 nl). Slow (30-min) injections of wheat germ-gold (1.00μl) were then made at the same coordinates, resulting in a restricted injection site corresponding to the Cl pressor area, verified by the presence of tyrosine hydroxylase- and neuropeptide Y-containing neurons. Transported gold was revealed by silver reduction, and enkephalin immunoreactive cells were revealed by immunocytochemistry. Enkephalin-positive gold-containing neurons were found primarily in the nucleus tractus solitarius, especially in the commissural and medial intermediate subnuclei. Cells in the nucleus tractus solitarius containing other transmitters (substance P, galanin, neuropeptide Y and catecholamines) did not show the same degree or pattern of double-labelling, suggesting that the transport was not due to non-specific silver reduction or spread from the pipette track. The potential importance of this endogenous intramedullary opiate system is discussed in terms of medullary control of the cardiovascular system. It is hypothesized that this opiate projection from the nucleus tractus solitarius to the rostral ventrolateral medulla could play an important modulatory function, influencing baroreceptor or other cardiopulmonary reflex pathways involved in the primary regulation of the cardiovascular system. Furthermore, this pathway could represent a central substrate underlying opiate effects on the cardiovascular system during such conditions as hemorrhagic shock, stress or opiate intoxication.

Chapter 8 Basis for the naturally occurring activity of rostral ventrolateral medullary sympathoexcitatory neurons

This chapter entertains two theories (network oscillator vs. intrinsic pacemaker) on the generation of the major component of SND - the 2- to 6-Hz rhythm in the cat and the 2- to 10-Hz rhythm in the rat. Evidence from experiments on cats strongly supports the hypothesis that the 2- to 6-Hz rhythm is an emergent property of a network oscillator located in the brain stem. Specifically, we propose that the 2- to 6-Hz component in SND arises from an ensemble of neurons of different types interconnected in such a way to generate the rhythm. There is no evidence for the existence of intrinsic pacemaker neurons in this network. Our experiments on cats also indicate that the rhythm is generated by neurons in the brain stem that are antecedent to RVLM-spinal SE and raphespinal-SI neurons. Our experiments on rats are not consistent with the hypothesis of Sun et al. (1988b) that "vasoconstrictor and cardioaccelerator sympathetic tone is due in large part to the intrinsic pacemaker activity of a small group of reticulospinal excitatory neurons located at the extreme anterior tip of the ventrolateral medulla". Rat RVLM pacemaker neurons act independently of each other following i.c. injection of the glutamate-receptor antagonist, KYN (Sun et al., 1988a). Thus, they would as a group provide white noise input to spinal neurons. It follows that i.c. KYN should have desynchronized SND if, as proposed by Sun et al., RVLM pacemakers are primarily responsible for SND in the rat. This was found not to be the case. The most likely explanation is that the 2- to 10-Hz rhythm in rat SND is not generated by intrinsic pacemaker neurons in the RVLM.

GABA-mediated inhibition of sympathoexcitatory neurons by midline medullary stimulation.

The present investigation determined whether the effects of electrical stimulation of depressor sites in midline medullary raphe nuclei were a result of inhibition of sympathoexcitatory medullospinal neurons in the rostral ventrolateral medulla of anesthetized cats. Electrical stimulation of the raphe inhibited inferior cardiac sympathetic activity. Microinjections of glutamate mimicked the effects of electrical stimulation. Electrical stimulation inhibited sympathoexcitatory neurons in the rostral ventrolateral medulla. The onset of the sympathoinhibition recorded from the inferior cardiac nerve (72 ms) was equal to the sum of the onset latency of the sympathoexcitatory response elicited from the rostral ventrolateral medulla (49 ms) plus the conduction time in the raphe to rostral ventrolateral sympathoinhibitory pathway (23 ms). Raphe stimulation excited a second set of neurons in the rostral ventrolateral medulla with an onset of 21 ms. Microiontophoretically applied bicuculline increased the discharge of sympathoexcitatory neurons and blocked the raphe-evoked inhibition. Iontophoretic glutamate excited sympathoexcitatory neurons but failed to antagonize raphe-elicited inhibition. These data suggest that neuronal elements in medullary raphe nuclei tonically inhibit sympathoexcitatory medullospinal neurons in the rostral ventrolateral medulla by activating closely adjacent gamma-aminobutyric acid (GABA) interneurons.

Depressor neurons in rabbit caudal medulla act via GABA receptors in rostral medulla.

Experiments were conducted in urethan-anesthetized rabbits to determine whether vasomotor effects elicited by activation or inhibition of the caudal ventrolateral medulla depend on gamma-aminobutyric acid (GABA)ergic, glycinergic, or alpha-adrenergic receptors in the region of the rostral ventrolateral medulla, which contains the bulbospinal sympathoexcitatory neurons. Bilateral injection of bicuculline methiodide into the rostral medulla caused a dose-related reduction in the fall in arterial pressure and in the inhibition of renal sympathetic nerve activity normally elicited by chemical stimulation of neurons in the caudal medulla using local injection of L-glutamate. When both bicuculline and muscimol were injected into the rostral medulla at the same time, resting arterial pressure was maintained at base-line levels, and the sympathoexcitatory neurons remained normally excitable by local injection of L-glutamate into the rostral medulla. In the presence of this mixed antagonist-agonist GABAergic blockade, both decreases and increases in arterial pressure elicited by excitation or inhibition of neuronal function in the caudal medulla were abolished. Similar effects were not observed after blockade of glycinergic or alpha-adrenergic receptors in the rostral ventrolateral medulla. Results suggest that the depressor neurons in the caudal ventrolateral medulla alter peripheral sympathetic vasomotor activity almost entirely by an action on GABAergic receptors in the rostral ventrolateral medulla.

The axons of raphespinal sympathoinhibitory neurons branch in the cervical spinal cord

This study shows that the axons of some raphespinal sympathoinhibitory neurons projecting to the third thoracic spinal segment emit branches in the third-fourth cervical spinal segments of cats. This was demonstrated by using time-controlled collision of neuronal action potentials initiated by stimuli applied at these spinal levels. Antidromic mapping revealed that the cervical branches of these neurons likely terminated in Rexed's lamina VII. In contrast to these raphe neurons, the axons of ventrolateral medullospinal sympathoexcitatory neurons did not emit cervical branches.

Sympathoexcitatory neurons of rostral ventrolateral medulla exhibit pacemaker properties in the presence of a glutamate-receptor antagonist

Intracisternal (i.c.) administration of the glutamate-receptor antagonist kynurenate to halothane-anesthetized rats (paralyzed, ventilated) produced an initial hypertension associated with an increase in lumbar sympathetic nerve discharge. Kynurenate (i.c.) blocked or greatly reduced all sympathetic reflexes investigated (somatosympathetic 70% reduction; vagal pressor and depressor responses, 100%; hypothalamic mixed responses, 90%; baroreflex, 100%) and increased the firing rate of retiiculospinal sympathoexcitatory cells of the rostral ventrolateral medulla (PGCL-SE neurons) by 33%. After i.c. kynurenate, these cells exhibited a rhythmic, non-bursting firing pattern which could be reset by spinal cord stimulation only when antidromic spikes were elicited. Cells with similar characteristics were recorded in the nucleus paragigantocellularis lateralis (PGCL) in an in vitro rat bulb preparation perfused through the basilar artery. Their ‘pacemaker-like’ discharge pattern was observed even in the absence of kynurenate and was reset by orthodromic activation. Cells with similar characteristics were also recorded within the PGCL in 500-μm coronal slices in vitro. At 37°C their discharge rate was similar to that of PGCL-SE neurons recorded in vivo after i.c. kynurenate; it was also pacemaker-like and was insensitive to glutamate receptor blockade. It is suggested that the tonic discharge of PGCL-SE neurons is normally due to an intrinsic pacemaker activity which is modulated in vivo by a variety of synaptic inputs.

Depressor neurons in rabbit caudal medulla do not transmit the baroreceptor-vasomotor reflex.

Experiments to determine whether depressor neurons in the caudal ventrolateral medulla form an integral part of the central pathway transmitting the baroreceptor-vasomotor reflex were performed on rabbits anesthetized with urethan. The function of the depressor neurons was altered by intramedullary injections of agents that stimulate or block receptors for gamma-aminobutyric acid and by electrolytic lesions in the caudal ventrolateral medulla. Muscimol abolished both the depressor response and the inhibition of renal nerve activity normally observed after stimulation of the aortic depressor nerve and caused a paradoxical reversal of the depressor response. However, muscimol only partially impaired the inhibition of renal nerve activity produced by experimental elevation of arterial pressure, and it did not affect the increase in renal nerve activity normally produced by decreasing arterial pressure. Bicuculline methiodide amplified the depressor response and the inhibition of renal nerve activity and also restored baroreceptor-vasomotor reflexes abolished by muscimol. Bilateral electrolytic lesions did not alter any component of the baroreceptor-vasomotor reflex. Results indicate that the depressor neurons in the caudal ventrolateral medulla do not form an integral part of the central pathway mediating the baroreceptor-vasomotor reflex. However, output from the depressor neurons appears to inhibit sympathoexcitatory neurons, which also receive baroreceptor-derived inhibitory inputs.

Inhibition of vasodepressor neurons in the caudal ventrolateral medulla of the rabbit increases both arterial pressure and the release of neuropeptide Y-like immunoreactivity from the spinal cord

The role of bulbospinal neuropeptide Y (NPY)-containing neurons of the rostral ventrolateral medulla in the rabbit in mediating the increase in blood pressure that occurs during inhibition of cells in the caudal ventrolateral medulla was investigated in urethane-anaesthetized rabbits. In the present experiments bilateral injections of the GABA agonist, muscimol, into the caudal ventrolateral medulla elicited a slowly-developing rise in arterial pressure that was maximal 15 min after the injection. Accompanying this increase in arterial pressure was an increase in the release of NPY-like immunoreactivity (NPY-LI) into the spinal subarachnoid space. This pattern of response is similar to that seen after direct chemical stimulation of the NPY-containing cells of the rostral ventrolateral medulla. Taken together, these findings suggest that tonically active neurons in the caudal ventrolateral medulla exert their effects by inhibiting sympathoexcitatory NPY-containing neurons whose cell bodies are situated in the rostral ventrolateral medulla.

Lateral tegmental field neurons of cat medulla: a source of basal activity of ventrolateral medullospinal sympathoexcitatory neurons.

We tested the hypothesis that neurons of the lateral tegmental field (LTF) of the cat medulla exert their sympathoexcitatory actions over a pathway that includes rostral ventrolateral medullospinal neurons innervating the spinal intermediolateral nucleus (IML). Thirty-one LTF neurons with sympathetic nerve-related activity [as demonstrated with spike-triggered averaging of inferior cardiac postganglionic sympathetic nerve discharge (SND)] were antidromically activated by microstimulation of the rostral ventrolateral medulla (VLM). The threshold current required to elicit the longest latency antidromic response was increased when the stimulating microelectrode was moved to more dorsal or medial sites in the rostral medulla. This observation suggests that the axons of LTF neurons projected to the rostral VLM. The firing rate of LTF neurons with sympathetic nerve-related activity was decreased during baroreceptor reflex activation. This observation is consistent with the view that these neurons subserved a sympathoexcitatory function. Twenty-five VLM neurons with sympathetic nerve-related activity were synaptically activated by microstimulation of the LTF. The modal onset latency of synaptic excitation (25.6 +/- 2.6 ms) compared favorably with the difference (31 ms on the average) between the firing times of LTF and VLM neurons relative to the peak of the cardiac-related sympathetic nerve slow wave. The firing rate of these VLM neurons decreased during baroreceptor reflex activation. Of nine VLM neurons tested, seven were antidromically activated by microstimulation of the second thoracic (T2) IML. These data are consistent with the view that LTF neurons are a source of the basal discharge of VLM-spinal sympathoexcitatory neurons. Sixteen VLM neurons with sympathetic nerve-related activity were antidromically activated by microstimulation of both the LTF and the T2 IML. In some cases, LTF stimulation activated an axonal branch rather than the main axon. This was demonstrated using time-controlled collision of the VLM neuronal action potentials initiated by LTF and T2 IML stimulation. These data raise the possibility that individual VLM neurons influence SND by actions mediated at both spinal and supraspinal levels.

Arterial baroreceptor and vagal inputs to sympathoexcitatory neurons in rat medulla.

Lumbar sympathetic nerve discharge and unit activity of reticulospinal sympathoexcitatory (SE) neurons located in nucleus paragigantocellularis lateralis (PGCL) were recorded in rats. The sympathoinhibition produced by low-frequency stimulation of vagal afferents was abolished by bilateral microinjections of 20 pmol of bicuculline methiodide (BIC, a GABA-receptor antagonist) into PGCL and was converted into a pressor response by injections of 100 pmol. These BIC injections also inhibited the arterial baroreflex in a dose-dependent manner. In contrast the sympathoexcitation produced by high-frequency stimulation of vagal afferents was selectively blocked by bilateral injections of kynurenic acid (KYN, a Glu-receptor antagonist) into PGCL. Convergence of vagal excitatory, vagal inhibitory, and arterial baroreceptor inputs was detected in all SE neurons recorded. Single-pulse stimulation of vagal afferents produced up to two peaks of excitation of SE neurons, both blocked by iontophoretic applications of KYN and at least one inhibitory period selectively blocked by iontophoresis of BIC. The results emphasize the importance of SE neurons and surrounding area in integrating the brain vasomotor output to spinal preganglionic neurons.

Hypothalamic glutamatergic input to medullary sympathoexcitatory neurons in rats.

In the halothane-anesthetized paralyzed rat, electrical or chemical stimulation of lateral hypothalamic sites dorsolateral to the fornix produced pressor effects, increases in lumbar sympathetic nerve discharge (SND), and excitation of the majority of bulbospinal sympathoexcitatory neurons of nucleus paragigantocellularis lateralis (PGCL sympathoexcitatory neurons). The relationship between SND and mean arterial pressure (MAP) was shifted upward by electrical hypothalamic stimulation, whereas the gain of the baroreflex was unchanged. A similar upward shift of the relationship between the discharge rate of PGCL sympathoexcitatory neurons and MAP was observed during stimulation. The excitatory effect of L-glutamate on PGCL sympathoexcitatory neurons was blocked by iontophoretic applications of kynurenic acid, whereas identical amounts of 8-OH kynurenic acid were ineffective. Bilateral pressure injections of kynurenic acid (but not of 8-OH kynurenic acid) into nucleus PGCL markedly reduced the pressor and sympathoexcitatory effects of hypothalamic stimulation without altering the on-going level of SND or its baroreflex inhibition. Applied by iontophoresis, kynurenic acid also attenuated the excitation of PGCL sympathoexcitatory neurons produced by hypothalamic stimulation. It is concluded that descending sympathoexcitatory pathways, originating in part in the lateral hypothalamus, relay in nucleus PGCL. This relay involves synapses that release an endogenous glutamate receptor agonist. These results suggest that synaptic integration between these glutamatergic inputs and gamma-aminobutyric acid baroreceptor inputs occurs in the immediate vicinity of PGCL bulbospinal sympathoexcitatory neurons or perhaps directly on their somadendritic surface.

A1 noradrenergic neurons tonically inhibit sympathoexcitatory neurons of C1 area in rat brainstem

In rats anesthetized with urethane and paralyzed, bilateral microinjections of kainic acid (KA) into the region of caudal ventrolateral medulla (CVL) containing noradrenergic neurons of the A1 group (A1 area) elicited a decrease followed by an increase in arterial pressure (AP), heart rate (HR) and sympathetic renal nerve activity (RNA). The sympathoinhibitory and sympathoexcitatory effects of KA were prevented by bilateral microinjection of tetrodotoxin into an area of the rostal ventrolateral medulla (RVL) containing C1 adrenergic neurons (the C1 area). In contrast, the automatic responses were not altered by interruption of the two other principal projections of A1 area neurons, namely to the hypothalamus or to the nucleus tractus solitarii. Bilateral microinjections of tyramine, clonidine, α-methylnoradrenaline or histamine into the C1 area elicited a dose-dependent, anatomically specific and reversible decrease in AP, HR and RNA. The effect of tyramine was blocked by previous microinjection of reserpine, 6-hydroxydopamine (6-OHDA), or phentolamine into the C1 area. Pretreatment with phentolamine unveiled a hypertensive effect of α-methylnoradrenaline. All effects of α-methylnoradrenaline were blocked by pretreatment of the C1 area with phentolamine plus dl-propranolol, whereas those elicited by histamine prevailed. Pretreatment of the C1 area with 6-OHDA abolished all changes in AP and HR elicited by microinjections of KA into the A1 area. We conclude that (1) neurons of the CVL tonically inhibit sympathetic activity, (2) this effect is mediated by an action upon vasomotor neurons of the C1 area of RVL, (3) the inhibition is mediated by noradrenergic projections from A1 neurons into the C1 area, and (4) this tonic sympathoinhibitory effect is independent of the baroreceptor reflex.

Medullospinal sympathoexcitatory neurons in normotensive and spontaneously hypertensive rats.

Aortic depressor nerve discharge (AND), lumbar sympathetic nerve discharge (SND), and single-unit activity of medullospinal pressure-sensitive neurons of nucleus paragigantocellularis lateralis (PGCL neurons) were recorded in halothane-anesthetized 16-wk-old spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats. The relationship between these variables and mean arterial pressure (MAP) was investigated. The gain of baroreceptor afferents was not significantly different between the strains, but corner MAP (intersection between linear ascending portion of curve and noise) was 38 mmHg higher in SHRs. The relationship between SND and MAP and that between PGCL neuronal activity and MAP were both characterized by a plateau (maximal activity) at low MAP followed by a linear reduction reaching zero at a level called cutoff MAP. The theoretical intersection between the plateau and the linear decremental portion of these curves was defined as a corner MAP. Values of corner MAP determined at the three levels (AND, SND, PGCL) were identical in a given strain and reset by a common value in SHRs (38-40 mmHg). The gain of baroreceptor reflex measured at all three sites as the slope of the linear incremental (AND) or decremental (PGCL and sympathetic chain) portion of the activity-MAP relationship was the same in WKY rats and in SHRs. Cutoff MAP measured in PGCL was identical to that measured in peripheral sympathetic system for a given strain. There was no significant difference in maximal discharge rate of PGCL neurons nor in lumbar SND and no interstrain difference in the proportion of SND that was suppressible by arterial baroreceptor feedback.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of clonidine and γ-Aminobutyric acid on the discharges of medullo-spinal sympathoexcitatory neurons in the rat

Single-unit recordings of 50 pressure-sensitive neurons with axonal projections to the thoracic spinal cord were obtained in the retrofacial portion of nucleus paragigantocellularis lateralis of halothane-anesthetized rats. Two types of cells were distinguished on the basis of their axonal conduction velocities: a slow-conducting (mean 0.6 m/s, group I) and a fast-conducting one (group II, mean 3.3 m/s). Both cell types were completely silenced by elevating mean arterial pressure above 160 mm Hg by means of aortic constriction and exhibited a plateau of high spontaneous activity below 70 mm Hg. Only group I neurons were significantly inhibited by the administration of clonidine in a dose producing 90% of its maximum hypotensive effect (11.5 micrograms/kg, i.v.). Hypotensive doses of clonidine administered into the fourth ventricle also produced a selective inhibition of group I neurons, while the others were unaffected. Iontophoretic applications of clonidine and norepinephrine produced an inhibition of the discharges of group I neurons qualitatively and quantitatively identical to that observed following administration of clonidine by the i.v. or i.c.v. route. Once more, group II cells were unaffected. In contrast, iontophoretically applied gamma-aminobutyric acid exerted a powerful inhibition of both cell types, an effect which was totally prevented or reversed by the gamma-aminobutyric acid antagonist bicuculline. Anatomical experiments were performed to uncover the potential source of catecholaminergic innervation of the area in which recordings were obtained. This area contains a large number of adrenaline-synthesizing neurons and receives a selective noradrenergic input from the A5 pontine group with no contribution from the A1, A2, A6 and A7 brainstem clusters of noradrenergic cells.

Electrophysiological study of sympathoexcitatory structures of the bulbar ventrolateral surface as related to vasomotor regulation

The responses in T3–4, T10–11 and L2–3 white rami to stimulation of different zones of the bulbar ventrolateral surface were maximal when the region of about 4 mm laterally to the midline was stimulated. A weak surface stimulation of all these zones elicited only a long latency response consisting of three waves. A short latency response appeared when supramaximal stimuli were applied only to the intermediate zone—the region up to 6 mm rostrally to the hypoglossal nerve root level (zone S and caudal part of zone M). The data presented show that long and short latency responses are conducted from the intermediate zone to the spinal cord via dorsolateral funiculus fibres with a conduction velocity of about 5.6 ± 0.6m/s. In addition, a special descending sympathoexcitatory pathway oriented to T2 preganglionic neurons with a conduction velocity of about 12.3 ± 3.2m/s was demonstrated. Antidromic discharges of the output sympathoexcitatory neurons elicited by dorsolateral funiculus stimulation were found in the intermediate zone only at a depth of about 400–2000 μ M. Stimuli applied to different regions of the ipsilateral bulbar ventrolateral surface activate at least two groups of surface fibres (conduction velocities 6.7–8.0 and 2–3.2m/s) which, in turn, activate the output neurons with a rather constant delay of about 20 ms equal to a difference between the latencies of long and short latency white rami responses. The mechanism of delay formation seems to be concentrated in the intermediate zone and formed probably by a chain of interneurons. A possible scheme of neuronal organization of the bulbar ventrolateral sympathoexcitatory structures is presented and discussed. The descending tonic activation of spinal vasomotor neurons is formed by spontaneous discharges of antidromically identified output neurons with a mean firing rate of about 14.4 imp./s. Some neurons are reflexly activated within the time limits of the late somatosympathetic reflex response. Coagulation of the intermediate zone resulted in a profound fall of blood pressure, disappearance of pressor and late somatosympathetic reflexes, whereas the spinobulbospinal somatosomatic reflex remains unchanged. The baroreceptor inhibition is partly realized through the elements of sympathoexcitatory intermediate zone because the preferable inhibition of the long latency white rami response was demonstrated in the middle of R-R interval and during a sharp increase in the arterial pressure induced by vasoconstrictor drugs. Thus, the structures of the intermediate zone seem to play a key role in supporting of blood pressure level and organization of pressure reflexes. They are suggested to be the actual elements of the bulbar vasomotor center.

Intrinsic γ-aminobutyric acid neurons in the nucleus of the solitary tract and the rostral ventrolateral medulla of the rat: An immunocytochemical and biochemical study

Sympathoexcitatory neurons in the C1 adrenergic area of the rostral ventrolateral medulla (RVL) are tonically inhibited by γ-aminobutyric acid (GABA). To identify the source of this GABAergic input, the distribution of neurons containing glutamate decarboxylase (GAD) was determined immunocytochemically in rats treated with colchicine. Numerous GAD-stained neurons were located in the nucleus of the solitary tract (NTS) and in RVL. Unilateral lesions in NTS did not alter GABA content or GAD activity in RVL, indicating that the afferent projection from NTS to RVL is not GABAergic. Intrinsic GABAergic neurons in RVL may provide tonic inhibition of vasomotor neurons in the C1 area.

Newly identified GABAergic neurons in regions of the ventrolateral medulla which regulate blood pressure

Glutamic acid decarboxylase (GAD), the enzyme which synthesizes the inhibitory transmitter gamma-aminobutyric acid (GABA), was localized immunocytochemically within cells and processes distributed throughout the ventrolateral medulla. In caudal regions, GAD-stained cells were adjacent to the ‘precerebellar’ lateral reticular nucleus and partially overlapped the A1 area of norepinephrine synthesizing neurons. The largest number of labeled neurons filled the rostral ventrolateral medulla (RVL), coinciding with and extending beyond the C1 adrenergic area. GAD-positive cells also occupied the nucleus reticularis parvocellularis, raphe magnus (RM) and lateral wings of RM in the region of the pararaphe. Intrinsic GAD-containing cells in the ventrolateral medulla may tonically inhibit sympathoinhibitory neurons in the caudal ventrolateral medulla (CVL) and sympathoexcitatory neurons in the RVL.

Axonal projection patterns of ventrolateral medullospinal sympathoexcitatory neurons.

We studied the following properties of cat ventrolateral medullary (VLM) neurons that projected to the thoracic spinal cord: the relationship between their spontaneous activity and that in the inferior cardiac postganglionic sympathetic nerve, their responses to baroreceptor-reflex activation, their axonal conduction velocities, the funicular trajectories of their axons, the likely sites of termination of their axons, and their axonal branching patterns. Microstimulation in the second thoracic spinal segment (T2) antidromically activated 67 VLM neurons (as determined with time-controlled collision of spontaneous and evoked action potentials), whose activity was correlated to inferior cardiac sympathetic nerve discharge (as determined with spike-triggered averaging). We tested the effect of baroreceptor-reflex activation on the firing rate of 20 of these VLM-spinal neurons. Because the firing rate decreased in each instance, these neurons apparently subserved a sympathoexcitatory function. The axonal branching patterns of 51 VLM-spinal sympathoexcitatory neurons were studied. Thirty-four neurons were antidromically activated by stimulation in the T2 gray matter and in more caudal thoracic spinal segments (T11 and/or T6). In each case, the antidromic response evoked by stimulation in the T2 gray matter was due to activation of an axonal branch rather than the main axon (via current spread to the white matter). This was demonstrated with tests that included time-controlled collision of the action potentials initiated by stimulation in T2 and a more caudal thoracic spinal segment. Some VLM-spinal axons that projected to T11 branched in T6 as well as in T2. These data indicate that some VLM-spinal neurons exerted widespread excitatory influences on sympathetic outflow. Seventeen VLM sympathoexcitatory neurons that innervated the T2 gray matter could not be antidromically activated by stimulation in T5, T6, and T11 despite an extensive search at each level. Thus the axonal projections of some VLM-spinal neurons were restricted to upper thoracic segments. Antidromic mapping in T2 revealed that the axons of VLM sympathoexcitatory neurons coursed through the dorsolateral or ventrolateral funiculus to innervate the region of the intermediolateral nucleus. Mean axonal conduction velocity was 3.5 +/- 0.3 m/s. Those VLM-spinal axons restricted to upper thoracic segments generally were located dorsally and/or medially to those that innervated widely separated thoracic segments. The discharges of 35 other VLM neurons that were antidromically activated by T2 stimulation were not related to sympathetic nerve activity.(ABSTRACT TRUNCATED AT 400 WORDS)