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R Y Moore

Publications and source records attributed to R Y Moore.

At least 37 records · Page 2Linked to original sources

Organization of neural inputs to the suprachiasmatic nucleus in the rat.

The circadian timing of the suprachiasmatic nucleus (SCN) is modulated by its neural inputs. In the present study, we examine the organization of the neural inputs to the rat SCN using both retrograde and anterograde tracing methods. After Fluoro-Gold injections into the SCN, retrogradely labeled neurons are present in a number of brain areas, including the infralimbic cortex, the lateral septum, the medial preoptic area, the subfornical organ, the paraventricular thalamus, the subparaventricular zone, the ventromedial hypothalamic nucleus, the posterior hypothalamic area, the intergeniculate leaflet, the olivary pretectal nucleus, the ventral subiculum, and the median raphe nuclei. In the anterograde tracing experiments, we observe three patterns of afferent termination within the SCN that correspond to the photic/raphe, limbic/hypothalamic, and thalamic inputs. The median raphe projection to the SCN terminates densely within the ventral subdivision and sparsely within the dorsal subdivision. Similarly, areas that receive photic input, such as the retina, the intergeniculate leaflet, and the pretectal area, densely innervate the ventral SCN but provide only minor innervation of the dorsal SCN. A complementary pattern of axonal labeling, with labeled fibers concentrated in the dorsal SCN, is observed after anterograde tracer injections into the hypothalamus and into limbic areas, such as the ventral subiculum and infralimbic cortex. A third, less common pattern of labeling, exemplified by the paraventricular thalamic afferents, consists of diffuse axonal labeling throughout the SCN. Our results show that the SCN afferent connections are topographically organized. These hodological differences may reflect a functional heterogeneity within the SCN.

Afferent Pathways↗

Identification of retinal ganglion cells projecting to the lateral hypothalamic area of the rat.

The objective of the present study was to identify the retinal ganglion cells projecting to the lateral hypothalamic area of the rat. The retinohypothalamic tract has been divided into a medial and a lateral component on anatomical and developmental grounds. The medial component projects to the suprachiasmatic nucleus and adjacent structures such as the anterior hypothalamic and retrochiasmatic areas. The lateral component terminates in the lateral hypothalamic are dorsal to the supraoptic nucleus. Injections of the retrograde tracer FluoroGold were made into the retinorecipient region of the lateral hypothalamic area and retinal whole mounts were immunohistochemically processed for retrogradely labeled retinal ganglion cells. With FluoroGold injections confined to the lateral hypothalamic area, retrogradely labeled retinal ganglion cells are located almost exclusively in the superior temporal quadrant of the retina. Their size and morphology indicates that they are a homogeneous subset of type III cells, but a definitive classification would require a more complete fill of dendritic arbors than is available in our retrograde material. In contrast, injections involving fibers of passage in the optic tract, or centered in the medial terminal nucleus of the accessory optic system, label cells distributed across the entire retinal surface. Unlike the retinal ganglion cells projecting to the suprachiasmatic nucleus [Moore et al., J. Comp. Neurol., 352 (1995) 351-366], the cells labeled after restricted lateral hypothalamic injections are not distributed evenly across the retinal surface. The difference in location of the retinal ganglion cells projecting to the lateral hypothalamic area supports the view that this retinohypothalamic projection is anatomically and functionally distinct from the projection to the suprachiasmatic nucleus and adjacent medial hypothalamus.

Animals↗

Forebrain activation in REM sleep: an FDG PET study.

Rapid eye movement (REM) sleep is a behavioral state characterized by cerebral cortical activation with dreaming as an associated behavior. The brainstem mechanisms involved in the generation of REM sleep are well-known, but the forebrain mechanisms that might distinguish it from waking are not well understood. We report here a positron emission tomography (PET) study of regional cerebral glucose utilization in the human forebrain during REM sleep in comparison to waking in six healthy adult females using the 18F-deoxyglucose method. In REM sleep, there is relative activation, shown by increased glucose utilization, in phylogenetically old limbic and paralimbic regions which include the lateral hypothalamic area, amygdaloid complex, septal-ventral striatal areas, and infralimbic, prelimbic, orbitofrontal, cingulate, entorhinal and insular cortices. The largest area of activation is a bilateral, confluent paramedian zone which extends from the septal area into ventral striatum, infralimbic, prelimbic, orbitofrontal and anterior cingulate cortex. There are only small and scattered areas of apparent deactivation. These data suggest that an important function of REM sleep is the integration of neocortical function with basal forebrain-hypothalamic motivational and reward mechanisms. This is in accordance with views that alterations in REM sleep in psychiatric disorders, such as depression, may reflect dysregulation in limbic and paralimbic structures.

Adult↗

Circadian rhythms: basic neurobiology and clinical applications.

Circadian rhythms are major features of adaptation to our environment. In mammals, circadian rhythms are generated and regulated by a circadian timing system. This system consists of entertainment pathways, pacemakers, and pace-maker output to effector systems that are under circadian control. The primary entertainment pathway is the retinohypothalamic tract, which terminates in the circadian pacemakers, the suprachiasmatic nuclei of the hypothalamus. The output of the suprachiasmatic nuclei is principally to the hypothalamus, the midline thalamus, and the basal forebrain. This provides a temporal organization to the sleep-wake cycle, to many physiological and endocrine functions, and to psychomotor performance functions. Disorders of circadian timing primarily affect entertainment and pacemaker functions. The pineal hormone, melatonin, appears to be promising agent for therapy of some circadian timing disorders.

Animals↗

Putative excitatory amino acid projections to the suprachiasmatic nucleus in the rat.

Retrograde axonal transport of the select neuronal tracer [3H]D-aspartate was used to demonstrate possible sources of excitatory input to the suprachiasmatic nucleus (SCN) in the albino rat. Following injection of [3H]D-aspartate into the SCN, neurons were retrogradely labeled in the infralimbic cortex, the lateral septal nucleus, the paraventricular thalamic nucleus, the medial preoptic area, the ventromedial, dorsomedial and posterior hypothalamic nuclei, the zona incerta, the intergeniculate leaflet and the ventral subiculum. Retinal ganglion cells, which project to the SCN and use glutamate as a neurotransmitter, were not labeled in our [3H]D-aspartate experiments, demonstrating a limitation of this method (i.e., false negatives). Our results show that the [3H]D-aspartate neuronal tracer labels a subset of areas known to project to the SCN, indicating these areas as likely sources of excitatory input to the SCN.

Animals↗

The sexually dimorphic nucleus of the hypothalamus contains GABA neurons in rat and man.

The sexually dimorphic nucleus of the preoptic area (SDN-POA) is the most striking structure displaying a morphological sex difference in the rat brain. A potentially homologous nucleus has been identified in the human hypothalamus. The objective of the present study was to pursue the putative homology of the rat and human SDN-POA by determining whether they express the same transmitter phenotype. We employed in situ hybridization histochemistry for GAD mRNA to show whether the neurons of the SDN-POA produce GABA. In both the rat and human, high levels of GAD65 and GAD67 mRNA are present in most, if not all, SDN-POA neurons. No sex difference is evident in the level of expression in either the rat or human. The data indicate that neurons of the SDN-POA in both the rat and human are GABA-producing and argue for the homology of these nuclei in the rat and human hypothalamus.

Animals↗

Neural control of the pineal gland.

The rhythm in melatonin production by the mammalian pineal gland is generated by the circadian timing system. The components of that system which mediate the function are: (1) visual projections through the retinohypothalamic tract to the circadian pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus; (2) the SCN which generates a circadian signal transmitted by SCN projections to the parvocellular autonomic component of the paraventricular nucleus; (3) paraventricular nucleus projections to the upper thoracic intermediolateral cell column; (4) preganglionic sympathetic fibers to the superior cervical ganglion; (5) postganglionic sympathetic fibers from the superior cervical ganglion to the pineal.

Animals↗

New insights into the mammalian circadian clock.

The focus of this review is recent studies of the mammalian circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus. The anatomy of the SCN and its major afferents from the retina, raphe, and intergeniculate leaflet (IGL) of the thalamus are considered, with a special emphasis on the effects of afferent interaction on the circadian timekeeping system. What is known of the endogenous clock mechanism is reviewed in comparison with known molecular circadian mechanisms in other species. Efferents of the SCN are also discussed with a view toward understanding how circadian information is transmitted to the rest of the central nervous system. Where possible, anatomical, electrophysiological, neuropharmacological, molecular, and behavioral data are integrated in an attempt to illuminate the mechanisms of circadian timekeeping.

Animals↗

Glutamic acid decarboxylase message isoforms in human suprachiasmatic nucleus.

The rat suprachiasmatic nucleus (SCN) is comprised of neurons that contain gamma-amino butyric acid (GABA) colocalized with one or more peptides. In the present study, the authors employed in situ hybridization histochemistry to determine whether the human SCN also contains GABA neurons using synthetic oligonucleotide probes complementary to sequences of two isoforms of the GABA-forming enzyme, glutamic acid decarboxylase (GAD), GAD65, and GAD67. Most, if not all, SCN neurons appear to express both GAD65 mRNA and GAD67 mRNA with the content of GAD67 greater than GAD65. Both isoforms also are expressed in some neurons of the anterior hypothalamic area, in small neurons of the paraventricular nucleus but not in the supraoptic nucleus. These data indicate that neurons in the human SCN, like those in rodents, use GABA as a neurotransmitter.

Animals↗

GABAA-receptor subunit composition in the circadian timing system.

In the present study, the distribution of GABAA-receptor alpha 1-, alpha 2-, alpha 3-, alpha 5-, beta 2.3- and gamma 2-subunits were localized immunohistochemically with subunit specific antibodies in the rat circadian timing system (CTS). The areas examined include the principal circadian pacemaker, the suprachiasmatic nucleus (SCN), and areas that receive important SCN input including the intergeniculate leaflet (IGL), subparaventricular zone (SPVZ), paraventricular hypothalamic nucleus (PVH), the retrochiasmatic area (RCh) and the paraventricular nucleus of the thalamus (PVT). The SCN has an unusual pattern with immunoreactivity for the alpha 2-, alpha 3-, alpha 5-, and gamma 2-subunits but not for the commonly expressed alpha 1- and beta 2.3-subunits. In all of the areas receiving SCN efferent input (SPVZ, PVH, RCh, PVT and IGL), staining is present either for all six subunits or for the three common subunits, alpha 1-, beta 2.3-, and gamma 2. There is some evidence for a differential distribution of subunits at the cellular level. The alpha 2-, and beta 2.3-subunits are predominantly expressed in neuropil, the alpha 3-, alpha 5- and gamma 2-subunits are predominantly expressed over perikarya and the alpha 1-subunit is expressed over both neuropil and perikarya in the areas in which subunit immunoreactivity is found. The demonstration of this regional and cellular expression of GABAA-receptor subunits should contribute to our understanding of GABAergic neurotransmission in the CTS.

Animals↗

Efferent projections of the paraventricular thalamic nucleus in the rat.

The paraventricular nucleus of the thalamus (PVT) receives input from all major components of the circadian timing system, including the suprachiasmatic nucleus (SCN), the intergeniculate leaflet and the retina. For a better understanding of the role of this nucleus in circadian timing, we examined the distribution of its efferent projections using the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L). The efferent projections of the PVT are loosely organized along its dorsal-ventral and anterior-posterior axes. The anterior PVT sends projections to the SCN; the dorsomedial and ventromedial hypothalamic nuclei; the lateral septum; the bed nucleus of the stria terminalis; the central and basomedial amygdaloid nuclei; the anterior olfactory nucleus; the olfactory tubercle; the nucleus accumbens; the infralimbic, piriform, and perirhinal cortices; the ventral subiculum; and the endopiriform nucleus. A small PHA-L injection, restricted to the ventral portion of the anterior PVT, produces a similar pattern of labeling, except for a marked decrease in the number of labeled fibers in the hypothalamus, cortex, and lateral septum and an increase in labeling in the endopiriform nucleus and basolateral amygdaloid nucleus. The posterior PVT has a more limited efferent distribution than the anterior PVT, terminating in the anterior olfactory nucleus; the olfactory tubercle; the nucleus accumbens; and the central, basolateral, and basomedial nuclei of the amygdala. Our results show that the anterior PVT is ideally situated to relay circadian timing information from the SCN to brain areas involved in visceral and motivational aspects of behavior and to provide feedback regulation of the SCN.

Amygdala↗

The retinohypothalamic tract originates from a distinct subset of retinal ganglion cells.

The retinal ganglion cells giving rise to retinohypothalamic projections in the rat were identified using retrograde transport of horseradish peroxidase (HRP) or FluoroGold injected into the suprachiasmatic nucleus (SCN), and using transneuronal transport of the Bartha strain of the swine herpesvirus (PRV-Bartha). When PRV-Bartha is injected into one eye, it is taken up by retinal ganglion cells, replicated, transported to axon terminals in the SCN, and released. There the virus may take one, or both, of two paths to retinal ganglion cells in the contralateral eye: 1) uptake by SCN neurons, replication, and release from the neurons with uptake and retrograde transport in retinal afferents originating in the contralateral retina; 2) transneuronal passage through axo-axonic appositions between retinal afferents in the SCN with subsequent retrograde transport of virus to the contralateral retina. The ganglion cells thus labeled are a homogeneous population of small neurons (mean diameter, 12.8 +/- 2.2 microns and mean area, 81.8 +/- 21.8 microns 2) with sparsely branching dendrites that are widely distributed over the retina. This population is best identified when virus labeling of retinal projections in areas beyond the hypothalamus is eliminated by lateral geniculate lesions that transect the optic tract at its entry into the geniculate complex. The same population is labeled with retrograde tracers but, with both HRP and FluoroGold, other ganglion cells are labeled, presumably from uptake by fibers of passage, indicating that the virus is a more reliable marker for ganglion cells giving rise to retinohypothalamic projections. The ganglion cells identified correspond to a subset of type III, or W, cells.

Animals↗

Organization of the mammalian circadian system.

The mammalian circadian timing system is a set of related neural structures whose function is to provide a temporal organization for physiological processes and behaviour. The system has three major components, entrainment pathways, pacemakers and output pathways that couple the pacemakers to effector systems that express circadian functioning. The retinohypothalamic tract is a direct retinal projection to the circadian pacemakers, the suprachiasmatic nuclei. The retinohypothalamic tract arises from a discrete set of retinal ganglion cells that receive photic information from a unique population of retinal photoreceptors and it mediates photic entrainment of the suprachiasmatic nuclei. The geniculohypothalamic tract arises from neurons of a specialized subdivision of the lateral geniculate complex, the intergeniculate leaflet. The intergeniculate leaflet and geniculohypothalamic tract appear to provide integrated photic and non-photic input to the suprachiasmatic nuclei to modulate pacemaker function. The suprachiasmatic nuclei comprise individual neuronal oscillators coupled into a neural network. The output of the suprachiasmatic nuclei is quite restricted but becomes amplified by a set of downstream components of the system that appear to provide a widespread circadian signal.

Animals↗

A putative retinohypothalamic projection containing substance P in the human.

The retinohypothalamic tract (RHT) is the principal pathway mediating the entraining effects of light on the circadian pacemaker, the suprachiasmatic nucleus (SCN). In the rat, the RHT has two components, one which projects to the SCN and the intergeniculate leaflet of the thalamus and has no known peptide content and one which projects to the SCN and, perhaps, to the olivary pretectal nucleus and contains substance P (SP). Both terminate predominantly in a zone of the SCN that contains vasoactive intestinal polypeptide (VIP)-producing neurons. In the human, there is a similar dense axonal plexus of SP-immunoreactive axons in the SCN located largely in the area occupied by VIP-immunoreactive neurons and distinct from other SP-immunoreactive axons in the area. We propose that this SP plexus represents a component of the RHT in the human brain.

Adult↗

Glutamate shifts the phase of the circadian neuronal firing rhythm in the rat suprachiasmatic nucleus in vitro.

The effect of glutamate (GLU) on the phase of the circadian neuronal firing rhythm of the rat suprachiasmatic nucleus (SCN) was examined in vitro. GLU application in late subjective night produces phase-advances whereas GLU applied in early subjective night produces either phase-delays or a bimodal peak in the firing rhythm that appears to be a combination of phase-advances and phase-delays. Optic chiasm (OC) stimulation, or exposure of animals to light just prior to sacrifice, produces phase-delays in early subjective night, and phase-advances in late subjective night. None of GLU, light and OC stimulation produces significant phase-changes during subjective day. The results indicate that GLU is the neurotransmitter of the retinohypothalamic tract.

Animals↗