David A. Ruggiero

Adrenaline neurons in the rostral ventrolateral medulla innervate thoracic spinal cord: A combined immunocytochemical and retrograde transport demonstration

Adrenaline-containing neurons in the C1 group of the ventrolateral rostral medullary reticular formation which project to the thoracic spinal cord were identified by a combined retrograde transport immunocytochemical technique. No other medullary catecholamine neurons, including the A1 and A2 noradrenaline cells, project to thoracic spinal cord. These data, taken with results of other studies of spinal catecholamine innervation, suggest a segmental segregation of projections to spinal cord by dopaminergic, noradrenergic, and adrenergic neurons.

Aromaticl-amino acid decar☐ylase in the rat brain: Immunocytochemical localization in neurons of the brain stem

Neurons containing the enzyme aromatic L-amino acid decarboxylase were immunocytochemically localized in the brain stem of the rat. The enzyme occurred as expected in previously well characterized monoaminergic cell groups, and in addition in some nuclei with unknown neurotransmitters. Major aggregates of neurons that were immunoreactive for aromatic L-amino acid decarboxylase but contained neither tyrosine hydroxylase nor serotonin, were found in the pretectal nuclei, the lateral parabrachial nucleus, and the dorsolateral subdivision of the nucleus tractus solitarius. Aromatic L-amino acid decarboxylase was also present in serotonin neurons and the majority of catecholamine cell groups. Dopamine, noradrenaline, and adrenaline cells exhibited characteristic staining intensities to anti-aromatic L-amino acid decarboxylase reflective of relative enzyme levels in the different groups. Some cells in the dorsal motor nucleus of the vagus that were previously classified as dopaminergic lacked immunoreactivity to aromatic L-amino acid decarboxylase.

Adrenaline synthesizing neurons in the rostral ventrolateral medulla: a possible role in tonic vasomotor control

Adrenaline-containing neurons of the rostral ventrolateral medulla (the C1 group) project selectively to autonomic spinal neurons in rats. Stimulation of these neurons electrically or chemically elevates arterial pressure, while neuronal blockade by microinjection of tetrodotoxin bilaterally drops arterial pressure to levels comparable to those produced by spinal cord transection. Adrenaline neurons of the ventral medulla appear necessary for maintaining normal levels of blood pressure, and thus may constitute a tonic vasomotor center.

Afferent projections to cardiovascular portions of the nucleus of the tractus solitarius in the rat

Horseradish peroxidase was injected unilaterally into the intermediate portion of the nucleus of the tractus solitarius. The most extensive retrograde labeling was present contralaterally in the rostral fastigial nucleus, bilaterally in the Koelliker-Fuse nucleus, and bilaterally with ipsilateral predominance in the posterolateral hypothalamus and paraventricular hypothalamic nucleus. These projections may represent the anatomical substrates by which these brain areas modulate baroreceptor reflex function.

Central control of the circulation by the rostral ventrolateral reticular nucleus: anatomical substrates

Publisher Summary Neurons in the rostral ventrolateral reticular nucleus (RVL), perhaps the hypothetical tonic vasomotor center, generate basal levels of sympathetic tone and arterial blood pressure (AP) and integrate cardiopulmonary and cerebrovascular reflexes. The critical zone precisely coincides a chemosensory area of the rostra1 ventrolateral quadrant, where most reticulospinal neurons projecting to the intermediolateral (IML) cosynthesize the putative neurotransmitters, adrenaline, and neuropeptide Y. Receptors in the RVL are responsive to a broad spectrum of cardioactive pharmacologic agents and the RVL is a major site of action of the imidazole, clonidine—a clinically effective antihypertensive drug. Nonetheless, still elusive is the identity of the neurotransmitter in RVL-generating sympathetic tone and whether it is, in fact, the C1 neurons of RVL that contribute to exaggerated sympathetic tone and, in turn, the circulatory changes involved in the initiation, expression, or maintenance of neurogenic hypertension. The RVL is the site of action for a broad spectrum of pharmacologic agents involved in cardiopulmonary control and derives its afferents from a variety of monoaminergic and peptidergic cell groups.

Glucagon gene regulatory region directs oncoprotein expression to neurons and pancreatic a cells

The regulatory region of the rat preproglucagon gene targets expression of the SV40 large T oncoprotein to two cell types in transgenic mice, the pancreatic alpha cells and a set of neurons localized in the hindbrain, both of which normally produce preproglucagon. Additional neurons in the forebrain and midbrain stain for T antigen but do not express the endogenous glucagon gene. Synthesis of T antigen in endocrine alpha cells results in the heritable development of pancreatic glucagonomas. In brains of transgenic mice from three independent lineages, expression of the hybrid gene begins at embryonic day 12 in neuroblasts of the hindbrain, where it continues throughout adult life, most notably in the medulla. Remarkably, oncoprotein expression in both proliferating neuroblasts and mature neurons has no apparent consequences, either phenotypic or tumorigenic. Expression of the hybrid glucagon gene in both neurons and islet cells supports a possible interrelationship between these cell types.

Electrical stimulation of cerebellar fastigial nucleus increases cerebral cortical blood flow without change in local metabolism: Evidence for an intrinsic system in brain for primary vasodilation

We sought to determine whether the increase in regional cerebral blood flow (rCBF) elicited by electrical stimulation of the fastigial nucleus of the cerebellum (FN) is secondary to, or independent of, increased local cerebral metabolism (rGMR) in anesthetized (chloralose) paralyzed rats. rCBF and rGMR were determined autoradiographically in separate groups of animals with comparable blood gases and systemic pressure, by the [14C]iodoantipyrine and [14C]2-deoxyglucose methods respectively. In sham-operated controls, rCBF (n = 5) and rGMR (n = 5) were closely related in the 28 brain areas studied (r = 0.733; P less than 0.005). During FN stimulation, rCBF (n = 6) increased significantly in 24 of the 28 areas, the greatest increase being in the cerebral cortex (up to 215%). rGMR (n = 9) increased in only 15 areas, so that the correlation between rCBF and rGMR throughout the brain became weaker (r = 0.568; P less than 0.005). Where the rCBF increases were the greatest (particularly in the cerebral cortex), rGMR was unchanged. This suggests that the rCBF increase was not a consequence of the increased rGMR. We conclude that neurons originating in or passing through FN may influence local cerebral circulation through a primary cerebral vasodilatation not coupled to metabolism.

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

Abstract 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.

Regional localization of agmatine in the rat brain: an immunocytochemical study.

The distribution of agmatine (decarboxylated arginine) was mapped in the central nervous system (CNS) in the rat. Agmatine-like immunoreactivity was identified by light microscopy, exclusively in the cytoplasm of neuronal perikarya. Immunoreactive neurons were present in the cerebral cortex, predominantly within laminae VI and V and, to a lesser extent, III and mainly in retrosplenial, cingulate, primary somatosensory and auditory cortices, and the subiculum. In the lower brainstem, immunoreactivity was selectively localized to visceral relay nuclei: the nucleus tractus solitarii and pontine parabrachial complex, and periventricular areas including the laterodorsal nucleus, locus coeruleus and dorsal raphe. In the midbrain, immunolabeled cells were concentrated in the ventral tegmental area and periaqueductal gray. In the forebrain, subcortical neurons were labeled predominantly in the preoptic area, amygdala, septum, bed nucleus of the stria terminalis, midline thalamus, and the hypothalamus. Ultrastructural analysis of layer V of the somatosensory cortex demonstrated agmatine-immunoreactivity in neurons, primarily in large dense-core vesicles located in the cytoplasm. Agmatine immunoreactivity was also affiliated with endoplasmic reticulum and the plasmalemma. Cortical neurons and the subiculum were labeled in animals not administered the axonal transport inhibitor, colchicine; thus, may normally contain higher concentrations of the amine than other brain regions. The central distribution of agmatine is consistent with the hypothesis that the amine may be a novel neurotransmitter of neurons involved in behavioral and visceral control.

Central and primary visceral afferents to nucleus tractus solitarii may generate nitric oxide as a membrane-permeant neuronal messenger

An anatomical basis was sought for the postulated roles of nitric oxide (NO) as a labile transcellular messenger in the dorsal vagal complex (NTS‐X). The diaphorase activity of NO synthase was used as a marker of neurons in NTS‐X that are presumed to convert L‐arginine to L‐citrulline and NO. Nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) staining patterns in the nucleus tractus solitarii (NTS) were spatially related to terminal sites of primary visceral afferents from 1) orosensory receptors (e.g., rostral‐central nucleus); 2) soft palate, pharynx, larynx, and tracheobronchial tree (e.g., dorsal, intermediate, and interstitial nuclei); 3) esophagus (nucleus centralis); 4) stomach (nucleus gelatinosus); 5) hepatic and coeliac nerves (nucleus subpostrema); and 6) carotid body and baroreceptors (medial commissural and dorsal‐lateral nuclei).