Biomedical subjects

Lawrence P Morin

Publications and source records attributed to Lawrence P Morin.

8 recordsLinked to original sources

PubMed2007

SCN organization reconsidered.

The SCN has long had organizational schemas imposed on it. In most, the SCN is dichotomized, with one region typically associated with the presence of vasopressin cells and the other associated with cells containing vasoactive intestinal polypeptide and certain afferent terminal fields. If assumed to be accurate, the schemas that have been intended to simplify and conceptually organize the known anatomy may actually interfere with the understanding of how various cell types and input pathways contribute to circadian rhythm regulation. This review describes inadequacies of existing schemas and notes several practical difficulties that undermine their usefulness. These include "static" versus "dynamic" anatomy, generalizations about SCN organization in relation to the plane or level of section, and the concept of differential density, all of which contribute to a view in which the SCN is substantially more complex than typically depicted in oversimplified line drawings. The need for accurate topographical description is emphasized.

Animals↗

PubMed2005

Medial vestibular connections with the hypocretin (orexin) system.

The mammalian medial vestibular nucleus (MVe) receives input from all vestibular endorgans and provides extensive projections to the central nervous system. Recent studies have demonstrated projections from the MVe to the circadian rhythm system. In addition, there are known projections from the MVe to regions considered to be involved in sleep and arousal. In this study, afferent and efferent subcortical connectivity of the medial vestibular nucleus of the golden hamster (Mesocricetus auratus) was evaluated using cholera toxin subunit-B (retrograde), Phaseolus vulgaris leucoagglutinin (anterograde), and pseudorabies virus (transneuronal retrograde) tract-tracing techniques. The results demonstrate MVe connections with regions mediating visuomotor and postural control, as previously observed in other mammals. The data also identify extensive projections from the MVe to regions mediating arousal and sleep-related functions, most of which receive immunohistochemically identified projections from the lateral hypothalamic hypocretin (orexin) neurons. These include the locus coeruleus, dorsal and pedunculopontine tegmental nuclei, dorsal raphe, and lateral preoptic area. The MVe itself receives a projection from hypocretin cells. CTB tracing demonstrated reciprocal connections between the MVe and most brain areas receiving MVe efferents. Virus tracing confirmed and extended the MVe afferent connections identified with CTB and additionally demonstrated transneuronal connectivity with the suprachiasmatic nucleus and the medial habenular nucleus. These anatomical data indicate that the vestibular system has access to a broad array of neural functions not typically associated with visuomotor, balance, or equilibrium, and that the MVe is likely to receive information from many of the same regions to which it projects.

Animals↗

PubMed2005

Descending projections of the hamster intergeniculate leaflet: relationship to the sleep/arousal and visuomotor systems.

The intergeniculate leaflet (IGL), homolog of the primate pregeniculate nucleus, modulates circadian rhythms. However, its extensive anatomical connections suggest that it may regulate other systems, particularly those for visuomotor function and sleep/arousal. Here, descending IGL-efferent pathways are identified with the anterograde tracer, Phaseolus vulgaris leucoagglutinin, with projections to over 50 brain stem nuclei. Projections of the ventral lateral geniculate are similar, but more limited. Many of the nuclei with IGL afferents contribute to circuitry governing visuomotor function. These include the oculomotor, trochlear, anterior pretectal, Edinger-Westphal, and the terminal nuclei; all layers of the superior colliculus, interstitial nucleus of the medial longitudinal fasciculus, supraoculomotor periaqueductal gray, nucleus of the optic tract, the inferior olive, and raphe interpositus. Other target nuclei are known to be involved in the regulation of sleep, including the lateral dorsal and pedunculopontine tegmentum. The dorsal raphe also receives projections from the IGL and may contribute to both sleep/arousal and visuomotor function. However, the locus coeruleus and medial vestibular nucleus, which contribute to sleep and eye movement regulation and which send projections to the IGL, do not receive reciprocal projections from it. The potential involvement of the IGL with the sleep/arousal system is further buttressed by existing evidence showing IGL-efferent projections to the ventrolateral preoptic area, dorsomedial, and medial tuberal hypothalamus. In addition, the great majority of all regions receiving IGL projections also receive input from the orexin/hypocretin system, suggesting that this system contributes not only to the regulation of sleep, but to eye movement control as well.

Afferent Pathways↗

PubMed2005

Functional analysis of the role of the median raphe as a regulator of hamster circadian system sensitivity to light.

The retinohypothalamic tract, a monosynaptic retinal projection to the suprachiasmatic nucleus (SCN), is the path by which light entrains the circadian system to the external photoperiod. Serotonergic neurons in the mesencephalic median raphe nucleus (MnR) also give rise to a major SCN afferent projection. The present study was designed to determine the extent to which MnR serotonergic projections regulate sensitivity of the circadian rhythm system to light. Serotonergic neurons in the MnR were destroyed by the direct application of the neurotoxin, 5,7-dihydroxytryptamine. Animals in constant darkness were given 5-min white light pulses at circadian time 19. Light intensity varied from 0.0011 to 70 microW/cm2. Assessment of rhythm phase response to light by lesioned and control animals revealed that animals lacking the MnR serotonergic projection are considerably more sensitive to light at high irradiances. The results are consistent with behavioral and physiological evidence implicating serotonin as an inhibitory modulator of the effects of light on circadian rhythmicity.

5,7-Dihydroxytryptamine↗

PubMed2005

Binocular contributions to the responsiveness and integrative capacity of the circadian rhythm system to light.

The retinohypothalamic tract (RHT), a monosynaptic retinal projection to the SCN, is the major path by which light entrains the circadian system to the external photoperiod. The circadian system of rodents effectively integrates or counts photons, and the magnitude of the rhythm phase response is proportional to the total energy of the photic stimulus. In the present studies, responsiveness to light and integrative capacity of the circadian system were tested in hamsters after reduction of retinal photoreceptor input by 50%. At CT 19, animals in constant darkness with or without unilateral retinal occlusion were exposed to 1 of 6 irradiances of 5-min white-light pulses ranging from 0.0011 to 70 microW/cm(2) or 5 white-light pulses of 0.6 microW/cm(2) with durations ranging from 0.25 to 150.0 min. Assessment of light-induced circadian rhythm phase response and Fos expression in the SCN by these animals revealed that a 50% reduction in input from photoreceptors stimulated directly with light caused a decrease in responsiveness to the longest duration and highest irradiance pulses presented. Despite this effect, both the magnitude of Fos induction in the SCN and phase-shift response remained directly proportional to the total energy in the photic stimuli. The results support the view that a reciprocal relationship between stimulus irradiance and duration persists despite the 50% reduction in retinal photoreceptor input. The mechanism of integration neither resides in the retina nor in the RHT.

Animals↗

PubMed2004

Intergeniculate leaflet and ventral lateral geniculate nucleus afferent connections: An anatomical substrate for functional input from the vestibulo-visuomotor system.

The intergeniculate leaflet (IGL) has widespread projections to the basal forebrain and visual midbrain, including the suprachiasmatic nucleus (SCN). Here we describe IGL-afferent connections with cells in the ventral midbrain and hindbrain. Cholera toxin B subunit (CTB) injected into the IGL retrogradely labels neurons in a set of brain nuclei most of which are known to influence visuomotor function. These include the retinorecipient medial, lateral and dorsal terminal nuclei, the nucleus of Darkschewitsch, the oculomotor central gray, the cuneiform, and the lateral dorsal, pedunculopontine, and subpeduncular pontine tegmental nuclei. Intraocular CTB labeled a retinal terminal field in the medial terminal nucleus that extends dorsally into the pararubral nucleus, a location also containing cells projecting to the IGL. Distinct clusters of IGL-afferent neurons are also located in the medial vestibular nucleus. Vestibular projections to the IGL were confirmed by using anterograde tracer injection into the medial vestibular nucleus. Other IGL-afferent neurons are evident in Barrington's nucleus, the dorsal raphe, locus coeruleus, and retrorubral nucleus. Injection of a retrograde, trans-synaptic, viral tracer into the SCN demonstrated transport to cells as far caudal as the vestibular system and, when combined with IGL injection of CTB, confirmed that some in the medial vestibular nucleus polysynaptically project to the SCN and monosynaptically to the IGL, as do cells in other brain regions. The results suggest that the IGL may be part of the circuitry governing visuomotor activity and further indicate that circadian rhythmicity might be influenced by head motion or visual stimuli that affect the vestibular system.

Animals↗

PubMed2003

Crossed and uncrossed retinal projections to the hamster circadian system.

The hamster suprachiasmatic nucleus (SCN), site of the circadian clock, has been thought to be equally and completely innervated by each retina. This issue was studied in animals that had received an injection of the tracer cholera toxin subunit B (CTb) conjugated to Alexa 488 into the vitreous of one eye, with CTb-Alexa 594 injected into the other. Retinal projections to the SCN and other nuclei of the circadian system were simultaneously evaluated by using confocal laser microscopy. Each retina provides completely overlapping terminal fields throughout each SCN. Although SCN innervation by the contralateral retina is slightly denser than that from the ipsilateral retina, there are distinct SCN regions where input from one side is predominant, but not exclusive. A dense terminal field from the contralateral retina encompasses, and extends dorsally beyond, the central SCN subnucleus identified by calbindin-immunoreactive neurons. Surrounding the dense terminal field, innervation is largely derived from the ipsilateral retina. The densest terminal field in the intergeniculate leaflet is from the contralateral retina, which completely overlaps the ipsilateral projection. Most nuclei of the pretectum receive innervation largely, but not solely, from the contralateral retina, although the olivary pretectal nucleus has very dense patches of innervation derived exclusively from one retina or the other. Retina-dependent variation in terminal field density within the three closely examined nuclei may indicate areas of specialized function not previously appreciated. This issue is discussed in the context of the melanopsin-containing retinal ganglion cell projections to several nuclei in the circadian visual system.

Animals↗

PubMed2003

Retinal ganglion cell projections to the hamster suprachiasmatic nucleus, intergeniculate leaflet, and visual midbrain: bifurcation and melanopsin immunoreactivity.

The circadian clock in the suprachiasmatic nucleus (SCN) receives direct retinal input via the retinohypothalamic tract (RHT), and the retinal ganglion cells contributing to this projection may be specialized with respect to direct regulation of the circadian clock. However, some ganglion cells forming the RHT bifurcate, sending axon collaterals to the intergeniculate leaflet (IGL) through which light has secondary access to the circadian clock. The present studies provide a more extensive examination of ganglion cell bifurcation and evaluate whether ganglion cells projecting to several subcortical visual nuclei contain melanopsin, a putative ganglion cell photopigment. The results showed that retinal ganglion cells projecting to the SCN send collaterals to the IGL, olivary pretectal nucleus, and superior colliculus, among other places. Melanopsin-immunoreactive (IR) ganglion cells are present in the hamster retina, and some of these cells project to the SCN, IGL, olivary pretectal nucleus, or superior colliculus. Triple-label analysis showed that melanopsin-IR cells bifurcate and project bilaterally to each SCN, but not to the other visual nuclei evaluated. The melanopsin-IR cells have photoreceptive characteristics optimal for circadian rhythm regulation. However, the presence of moderately widespread bifurcation among ganglion cells projecting to the SCN, and projection by melanopsin-IR cells to locations distinct from the SCN and without known rhythm function, suggest that this ganglion cell type is generalized, rather than specialized, with respect to the conveyance of photic information to the brain.

Animals↗