Biomedical subjects

R Y Moore

Publications and source records attributed to R Y Moore.

At least 55 records · Page 3Linked to original sources

PubMed1994

Intergeniculate leaflet: an anatomically and functionally distinct subdivision of the lateral geniculate complex.

The intergeniculate leaflet (IGL) in the rat is a distinctive subdivision of the lateral geniculate complex that participates in the regulation of circadian function through its projections to the circadian pacemaker, the suprachiasmatic nucleus (SCN) of the hypothalamus. The present investigation was undertaken to provide a precise definition of the IGL and a characterization of its neuronal organization including neuronal morphology, chemical phenotype, connections, and synaptic organization. The IGL extends the entire rostrocaudal length of the geniculate complex and contains a distinct population of small to medium neurons. In Golgi preparations, the neurons are multipolar with dendrites largely confined to the IGL. The neurons can be subdivided into three groups on the basis of neurotransmitter content and projections: (1) neurons that contain GABA and neuropeptide Y and project to the SCN; (2) neurons that contain GABA and enkephalin and project to the contralateral IGL; and (3) a small group of neurons that projects to the SCN but not characterized as yet by neurotransmitter content. The IGL receives dense, bilateral input from retinal ganglion cells and dense substance P input of unknown origin. A number of neurons in the anterior hypothalamic area and, particularly, the retrochiasmatic area project to the IGL, and there are sparse projections from brainstem monoamine and cholinergic neurons. The synaptic organization of the IGL is complex with afferents terminating in glomerular complexes that include axoaxonic synaptic interactions. Virtually all IGL afferents synapse upon dendrites and spines, with the densest synaptic input occurring on the distal portions of the dendritic arbor. The organization of the IGL and its connections as revealed in this analysis is in accord with its role in the integration of visual input with other information to provide feedback regulation of the SCN pacemaker.

Animals↗

PubMed1994

Responses of rat suprachiasmatic nucleus neurons to substance P and glutamate in vitro.

The suprachiasmatic nucleus (SCN), a circadian pacemaker in the mammalian brain, receives photic information directly from the retina via the retinohypothalamic tract (RHT). Although the neurotransmitters of the RHT have not yet been identified, it is known that glutamate (Glu) and substance P (SP) are present in RHT axons. We report the responses of spontaneously firing SCN neurons to Glu and SP examined in isolated brain slices. 43% of the neurons show an excitatory response (an increase in firing rate) and 11% an inhibitory response to bath-applied SP at a concentration of 10(-7) M. Glu evokes excitatory responses from SCN neurons in a dose-dependent manner (10(-6)-10(-4) M). No day-night difference is observed in the response of SCN neurons either to 10(-7) M SP or to 10(-4) M Glu. Bath-applied SP has additive effects on Glu-evoked responses and pressure-ejected SP at a concentration of 0.8 mM strongly potentiates Glu responses. These results are consistent with the view that Glu and/or SP function as neurotransmitters, or modulators, in the RHT and suggest that cellular processes downstream of the activation of SP or Glu receptors mediate time-dependent phase responses of SCN neurons.

Animals↗

PubMed1994

Morphological correlates of circadian rhythm restoration induced by transplantation of the suprachiasmatic nucleus in hamsters.

A compelling body of evidence indicates that the suprachiasmatic nucleus (SCN) of the hypothalamus is a pacemaker in the rodent circadian timing system. Two important components of this evidence are studies showing that SCN lesions abolish circadian rhythms and others demonstrating restoration of circadian activity rhythms after transplantation of fetal SCN into the brains of arrhythmic hosts. In the present study, we evaluated what has remained a persisting issue in this transplant literature, the extent to which the exact localization and organization of the transplants is critical to their capacity to restore circadian function in the hamster. The data obtained indicate that the location of the graft in the ventricular system is not crucial to outcome. Grafts in the lateral ventricle, dorsal third ventricle, interventricular foramen, and caudal third ventricle are as capable of restoring circadian function as ones placed in the ventral third ventricle in the vicinity of the lesion. Restoration of rhythmicity does require that the grafts contain a minimum volume of SCN-like tissue as defined by cytoarchitecture and the presence of vasopressin--and vasoactive intestinal polypeptide (VIP)--immunoreactive cells and fibers. There is also an indication that VIP-immunoreactive elements are the component critical to functional recovery. Connections between graft and host are evident in the immunohistochemical material but are quite variable in extent and often very limited. Thus, the data obtained in this study are consistent with the view that restoration of circadian function by fetal grafts requires the presence of SCN, and probably VIP-containing neurons, but does not depend upon the exact location of the graft or the presence of specific connections between graft and host.

Animals↗

PubMed1994

Projections of the suprachiasmatic nuclei, subparaventricular zone and retrochiasmatic area in the golden hamster.

The patterns of projections from the hamster suprachiasmatic nucleus, retrochiasmatic area and subpraventricular hypothalamic zone were examined using anterograde tracing with the plant lectin, Phaseolus vulgaris leucoagglutinin. Suprachiasmatic nucleus efferents comprise four major fiber groups: (i) an anterior projection to the ventral lateral septum, the bed nucleus of the stria terminalis and anterior paraventricular thalmus; (ii) a periventricular hypothalamic projection extending from the preoptic region to the premammillary area; (iii) a lateral thalamic projection to the intergeniculate leaflet and ventral lateral geniculate; and (iv) a posterior projection to the posterior paraventricular thalamus, precommissural nucleus and olivary pretectal nucleus. The retrochiasmatic area showed a similar projection pattern with several major exceptions. There are projections to endopiriform cortex, fundus striati, ventral pallidum, horizontal limb of the nucleus of the diagonal band and three separate routes to the amygdala. There are also projections laterally with fibers of the supraoptic commissures, which enter the superior thalamic radiation and innervate the caudal dorsomedial thalamic nuclei. Other fibers traveling with the commissures terminate in the ventral zona incerta. The subparaventricular zone projects to most targets of the suprachiasmatic nucleus, but not to the intergeniculate leaflet. There is a substantial input to both the subparaventricular zone and retrochiasmatic area from the suprachiasmatic nucleus, but little apparent reciprocity. There is extensive overlap of suprachiasmatic nuclei and retrochiasmatic efferents, and between retrochiasmatic and known medial amygdaloid efferents. The anatomical information is discussed in the context of circadian rhythm regulation, photoperiodism and chemosensory pathways controlling male hamster reproductive behavior.

Animals↗

PubMed1994

Calmodulin inhibitors produce phase shifts of circadian rhythms in vivo and in vitro.

The effect of calmodulin inhibitors on the circadian rhythm of locomotor activity and on the rhythm of suprachiasmatic nuclear (SCN) neuron firing rate recorded in vitro from hypothalamic slices was examined. Trifluoperazine produces changes in a dose-dependent manner in the phase of the activity rhythm, with phase advances throughout most of the subjective day extending into the subjective night. These phase changes in the activity rhythm occur rapidly and without induction of locomotor activity at the time of treatment. Similarly, trifluoperazine and the naphthalenesulfonamide W-7 produce changes in phase delays in the subjective night extending into early subjective day. The effects are greater with respect to amplitude when measured acutely after treatment than in the next cycle, and both the acute and next-day effects are greater than those observed in vivo, indicating that data from in vitro studies need to be interpreted with caution. These observations indicate that calmodulin inhibitors affect rhythms directly in vivo by altering SCN neuron pacemaker function, as this reflects involvement of calcium-calmodulin binding with activation of a calmodulin-dependent kinase, either to alter intracellular cAMP levels or to alter gene expression directly to modulate the phase of the SCN clock.

Animals↗

PubMed1993

Retinohypothalamic tract development in the hamster and rat.

The development of the retinohypothalamic tract (RHT) in the albino rat and golden hamster was studied using anterograde transport of cholera toxin conjugated to horseradish peroxidase (CT-HRP). The RHT has three components in the adult: (1) a dense projection to the ventrolateral subdivision of the suprachiasmatic nucleus (SCN) with some fibers extending into the dorsomedial SCN; (2) a projection to adjacent areas, the anterior hypothalamic area (AHA) and retrochiasmatic area (RCA) and in the hamsters, into the preoptic area (POA); (3) a projection to the lateral hypothalamic area (LHA). In the rat, the projection to the SCN and adjacent areas first appears as scattered varicosities at the ventral border of the SCN at postnatal day 1 (P1) and gradually increases until the adult pattern is achieved at approximately P10. The projections to the AHA and RCA are seen first at P2-P3 and gradually increase to the adult appearance by P15. Both the projection to the SCN and adjacent areas and to the LHA, initially are more extensive than in the adult. Many of the axons extend well beyond the zone of the adult pattern but these anomalous fibers are eliminated by P6-P10. The LHA projection first appears at embryonic day 21-22 (E 21-22) and gradually increases in density from P1-P6. In the hamster the projections to the SCN, AHA and LHA appear first on P4 and gradually increase in density to reach the adult pattern by P15. The projections to the RCA and POA are present by P6 and reach the adult pattern by P15. None of the RHT projections in the hamster has the initial extended growth followed by pruning back that characterizes RHT development in the rat. Thus, the development of the RHT in both the rat and the hamster is complex with components of the projection appearing at different times with differing patterns of development that indicate specialized interactions of the developing axons with their target neurons. Synaptogenesis in the hamster hypothalamus was analyzed using an antiserum to synapsin I. Few synapses are present at E16, the last day of gestation, in the LHA, SCN and AHA. From P1-P3, synaptogenesis proceeds rapidly and the adult pattern is achieved in all three areas by P4.

Animals↗

PubMed1993

Principles of synaptic transmission.

Neurons in the central nervous system communicate almost exclusively by the production and release at synapses of a series of molecules that are designated transmitters. Three such molecules make up the major transmitters, GABA, glutamate, and acetylcholine. GABA neurons are the principal inhibitory neurons and, as such, are the major local circuit neurons of the brain. They also are projection neurons in a number of systems. Glutamate neurons are excitatory projection neurons, particularly of the cerebral cortex, thalamus and retina. Acetylcholine neurons are excitatory neurons in ascending brainstem and basal forebrain systems and in cranial and spinal motor neurons and neurons of the sympathetic and parasympathetic systems. The catecholamines, dopamine and norepinephrine, are transmitters in several systems in brain. Dopamine is present in midbrain neurons projecting to the neostriatum, basal forebrain and cerebral cortex. It is also produced by hypothalamic neurons projecting to the median eminence and pituitary. These systems are highly topographically organized in contrast to the norepinephrine systems. The locus coeruleus norepinephrine system projects principally to thalamus, cerebral cortex and cerebellar cortex whereas the lateral tegmental system projects primarily to basal forebrain, hypothalamus, brainstem and spinal cord. The serotonin neurons of the brainstem raphe also project widely over the neuraxis, midbrain raphe neurons primarily to diencephalon and telencephalon and pontine medullary neurons to brainstem and spinal cord. There are smaller neuronal groups that produce glycine or histamine. At the present time, it appears that most, if not all, CNS neurons produce one of these small molecule transmitters. In many instances, these molecules are colocalized with one or more peptides that appear to modify the postsynaptic action of the small molecule transmitter.

Acetylcholine↗

PubMed1993

Neuropeptide Y and optic chiasm stimulation affect suprachiasmatic nucleus circadian function in vitro.

The retinohypothalamic tract (RHT) is a direct pathway from the retina to the suprachiasmatic nucleus (SCN). Electrical stimulation of the optic nerve or optic chiasm activates the RHT and produces shifts in phase of a circadian rhythm in SCN neuron activity in rat hypothalamic slices in vitro. The phase response curve (PRC) for this effect is very similar to that obtained from administration of light pulses to intact animals maintained in constant darkness. The effect of optic chiasm stimulation is blocked by tetrodotoxin. In addition to the RHT, there is a second entraining pathway, the geniculohypothalamic tract, which arises from neuropeptide Y (NPY)-containing neurons of the intergeniculate leaflet of the lateral geniculate complex. In contrast to optic chiasm stimulation. NPY produces phase shifts in the rhythms of SCN neuron firing rate in vitro with a PRC that similar to that for NPY infusion into the SCN in intact animals as well as that produced by a series of treatments that induce locomotor activity. These results indicate that phase shifts of the circadian rhythm of SCN neuron activity may be produced by activation of two different entraining pathways and that the physiological actions of these pathways on pacemaker function are markedly different.

Animals↗

PubMed1993

Tetrodotoxin does not affect circadian rhythms in neuronal activity and metabolism in rodent suprachiasmatic nucleus in vitro.

Single unit activity of suprachiasmatic nucleus (SCN) neurons recorded from hamster and rat hypothalamic slices in vitro exhibits a circadian rhythm in firing rate. Tetrodotoxin (TTX) produces electrical silence during the period of administration but has no effect on the oscillatory activity of the circadian pacemaker in both hamster and rat SCN. TTX does not affect either the phase of the rhythm in firing rate at any time of the circadian day, or that of the rhythm in glucose metabolism as demonstrated by the 2-deoxyglucose method. These data are in accord with the view that SCN neuron firing rate and glucose utilization is an expression of pacemaker activity but that pacemaker function is maintained in the SCN independent of neuronal function manifested by sodium dependent action potentials.

Animals↗

PubMed1993

GABA is the principal neurotransmitter of the circadian system.

The circadian timing system imposes a temporal organization on physiological processes and behavior. The two major nuclei of the system are the intergeniculate leaflet (IGL) of the lateral geniculate complex and the suprachiasmatic nucleus (SCN) of the hypothalamus. In this study, we demonstrate that neurons of both nuclei colocalize GABA with peptides. In the IGL, GABA is colocalized with neuropeptide Y in neurons projecting to the SCN and with enkephalin in neurons projecting to the contralateral IGL. In the SCN, GABA is colocalized with vasopressin and vasoactive intestinal polypeptide. All, or nearly all, of the neurons in the IGL and SCN are GABA-producing. Thus, GABA should be considered the principal neurotransmitter of the circadian system.

Animals↗

PubMed1993

Organization of the primate circadian system.

The circadian timing system has three principal elements: the retina, the intergeniculate leaflet (IGL) of the thalamus, and the suprachiasmatic nucleus (SCN). Since the human circadian timing system cannot be studied experimentally, we have used another primate, the macaque monkey, to help provide insight into the organization of the human circadian system. The retinohypothalamic tract (RHT) in the monkey projects to the SCN, the anterior and lateral hypothalamic areas, and the retrochiasmatic area in a pattern very similar to that in the rat. The monkey SCN has a population of vasoactive intestinal polypeptide-containing (VIP+) neurons in a zone that overlaps the RHT termination and the termination of neuropeptide Y-containing (NPY+) axons arising in the IGL. This zone is surrounded by a population of vasopressin-containing (VP+) neurons. The human SCN is similar to that of other mammals with populations of VIP+ and VP+ neurons, but it differs in having a large population of neurotensin-containing (NT+) neurons that extends over the entire nucleus, and a moderate population of NPY+ neurons located centrally in the nucleus in the presumed area of RHT termination. The lateral geniculate nucleus in the monkey and human is quite different from that in rodents, but contains an area in the pregeniculate nucleus that receives bilateral retinal projections in the monkey and is characterized in both the monkey and human by a population of NPY+ neurons and a plexus of enkephalin- and substance P-containing axons. This nucleus appears homologous to the rodent IGL.

Animals↗

PubMed1992

Morphological and functional development of the suprachiasmatic nucleus in transplanted fetal hypothalamus.

The development of the suprachiasmatic nucleus (SCN) in fetal rat hypothalamus transplanted to the adult brain was studied using morphological and functional methods. Anterior hypothalamic tissue was transplanted into the third ventricle, lateral ventricle or subarachnoid space of intact, adult hosts from E17 fetuses. These transplants developed the cytoarchitectonic and immunohistochemical staining characteristics of SCN, clusters of parvocellular neurons expressing vasopressin- and vasoactive intestinal polypeptide-like immunoreactivity in adjacent cellular populations, irrespective of the exact location of the transplanted tissue in the host brain. The functional status of the transplants placed in the rostral third ventricle and the foramen of Monroe was analyzed and compared to host SCN using in vitro recording of neuronal firing rate and measurement of metabolism using the 2-deoxyglucose (2-DG) technique. During subjective day, neuronal firing rates and 2-DG uptake were high in discrete cell groups within the transplants which were subsequently demonstrated to exhibit the cytoarchitectonic and immunohistochemical characteristics of SCN. The firing rates and 2-DG uptake in these areas were lower during the subjective night. This pattern of activity closely resembles that of the intact SCN. In contrast, neither transplanted anterior hypothalamic area, lacking an identifiable SCN-like structure, nor posterior hypothalamic area showed day-night differences in firing rate or 2-DG uptake. These observations indicate that SCN transplanted into intact adult hosts exhibits morphological and functional differentiation nearly identical to the host and that the transplanted SCN maintains circadian function which is probably entrained to the host SCN.

Action Potentials↗

PubMed1992

Intergeniculate leaflet and suprachiasmatic nucleus organization and connections in the golden hamster.

The intergeniculate leaflet (IGL) is a distinct subdivision of the lateral geniculate complex which receives retinal input and projects upon a circadian pacemaker, the suprachiasmatic nucleus (SCN). In the present study, we have analyzed the organization of the IGL and its connections in the hamster, a species commonly used in circadian rhythm studies. The location of the IGL is defined by the presence of retinal afferents demonstrated by anterograde transport of cholera toxin-HRP, neuropeptide Y-containing neurons and axons, cells retrogradely labeled from the regions of the SCN and contralateral IGL, and substance P-containing axons. It is a long nucleus extending the entire rostrocaudal axis of the geniculate. The most rostral IGL lies between the lateral dorsal thalamus, ventrolateral part, and the horizontal cerebral fissure. It then enlarges ventral to the rostral dorsal lateral geniculate, medial to the optic tract. The mid-portion of the leaflet is a thin lamina intercalated between the dorsal and ventral geniculate nuclei. The extended caudal portion of the nucleus lies lateral and ventral to the medial geniculate and is contiguous with the zona incerta and the lateral terminal nucleus. The IGL contains populations of neuropeptide Y (NPY+) and enkephalin (ENK+) neurons which project to the retinorecipient portion of the SCN. In addition to the immunoreactive perikarya, the IGL contains plexuses of NPY+, ENK+, substance P-, serotonin-, and glutamic acid decarboxylase-immunoreactive axons. Retrograde transport studies demonstrate that, in addition to the NPY+ neurons, there is a population of non-NPY+ neurons projecting upon the SCN.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗

PubMed1992

Behavioral and morphological studies of fetal neural transplants into SCN-lesioned rats.

We have studied the effects of fetal neuronal grafts on the temporal pattern of drinking behavior of suprachiasmatic nuclei (SCN)-lesioned adult rats. Additionally, in an independent set of animals, the immunohistochemical staining for vasopressin, vasoactive intestinal polypeptide, and neuropeptide Y and the retinal connections to the hypothalamus were studied. The behavioral experiments indicate that anterior hypothalamic transplants induced reorganization of the temporal pattern of drinking behavior when placed in the third ventricle of adult hosts bearing complete SCN lesions, but not when placed in a cavity in the occipital cortex. Such rhythmicity persists only when the animals were recorded under constant darkness but not under constant light, indicating that the restored rhythmicity was generated endogenously but that the oscillator was extremely sensitive to light. Fetal occipital cortex induced reorganization of the temporal pattern of previously arrhythmic hosts, but it disappeared when the animals were recorded under constant light or constant darkness. It is clear that this rhythmicity was exogenous. In contrast to the cortical transplants, the hypothalamic transplants showed a morphological organization similar to that found in the normal hypothalamus regardless of their placement in the host brain. From these observations it is concluded that development of neocortex is more affected by environmental factors than that of the hypothalamus. Both hypothalamic and cortical transplants induced sprouting of retinal fibers into the anterior hypothalamus and the grafted tissue. It is possible that such fibers could be the neuroanatomical substrate by which rhythmicity is induced by cortical tissue.

Animals↗

PubMed1992

The fourth C.U. Ariëns Kappers lecture. The organization of the human circadian timing system.

The mammalian circadian timing system has three principal components; (1) photoreceptors and visual pathways mediating entrainment; (2) a pacemaker, the suprachiasmatic nucleus of the hypothalamus; and (3) efferent pathways coupling the suprachiasmatic nucleus to effector systems exhibiting circadian function. In most mammals there are two visual entraining pathways, a direct retinohypothalamic pathway terminating in the suprachiasmatic nucleus, for which the transmitter is unknown, and a secondary visual pathway, the geniculohypothalamic tract, from the intergeniculate leaflet of the lateral geniculate to the suprachiasmatic nucleus that is neuropeptide Y-producing. These pathways end in a distinct subdivision of the suprachiasmatic nucleus characterized by the presence of vasoactive intestinal polypeptide neurons. A second suprachiasmatic nucleus division does not receive visual afferents and is characterized by vasopressin neurons. The efferent projections of the suprachiasmatic nucleus are very restricted, predominantly to the hypothalamus. Although we have much less information on the human circadian timing system than on that of other animals, it seems clear that the human conforms to the general animal pattern in most features. There are, however, two significant differences. First, the largest neural component of the human suprachiasmatic nucleus is a population of neurotensin neurons found throughout the nucleus. Few, if any, neurotensin neurons are found in monkey or other mammals. Second, the human suprachiasmatic nucleus contains a large number of neuropeptide Y neurons located where the plexus arising from geniculate neuropeptide Y neurons is found in other mammals. This is unique and suggests that the geniculohypothalamic projection may be bypassed in the human. It also may imply that the functional organization of the human SCN is fundamentally different from that of other mammals. The function of the circadian timing system is to coordinate the activities of a series of homeostatic regulatory mechanisms with the control of behavioral state in a temporal pattern that facilitates adaptive behavior, including reproduction (Fig. 9). The function of this system, then, is to provide the appropriate physiological and behavioral background to facilitate adaptation and survival.

Animals↗

PubMed1992

Analysis of in vitro glucose utilization in a circadian pacemaker model.

An in vitro glucose utilization method, based upon 14C-2-deoxyglucose kinetics in brain slices, has been used to study circadian rhythms in hypothalamic slices containing the suprachiasmatic nucleus (SCN). Spontaneous SCN metabolic activity in vitro is similar to that observed in vivo with higher metabolic rates in subjective daytime and lower rates during subjective night. However, in vitro SCN metabolic activity during late subjective day is above that seen when glucose utilization is measured in vivo, suggesting that an inhibitory influence normally active in vivo is lost during slice isolation. Incubation of slices containing SCN in the presence of TTX exposes a TTX-insensitive component of metabolic activity in early subjective day, supporting prior suggestions that glucose utilization by the circadian oscillator continues in the absence of Na(+)-dependent action potentials. Studies with high Mg2+ concentrations are consistent with the hypothesis that most metabolic activity above the basal level observed with the glucose utilization method is related to synaptic activity. Pharmacological studies of the SCN brain slice model with radiotracers offer potential for analysis of both circadian rhythmicity and neural regulation.

Animals↗

PubMed1991

Immunocytochemical characterization of the suprachiasmatic nucleus and the intergeniculate leaflet in the diurnal ground squirrel, Spermophilus lateralis.

The suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) are retinorecipient structures that play important roles in the expression of circadian rhythmicity. We examined these two structures in a diurnal ground squirrel, Spermophilus lateralis, using immunohistochemical techniques, and cholera toxin-bound horseradish peroxidase. A number of immunoreactive substances are distributed within the ground squirrel SCN in a pattern similar to that reported in many other mammals. These include vasopressin, vasoactive intestinal polypeptide, serotonin, neuropeptide Y (NPY), and glial fibrillary acidic protein. The squirrel SCN differs from that of most other species examined to date in two respects. First, a dense cluster of cells containing immunoreactive L-enkephalin (L-ENK-IR) is observed in the center of the SCN. Second, there is a contralateral, but no ipsilateral, projection from the retina to the SCN. In the lateral geniculate region there is a substantial region that contains NPY-immunoreactive cells and receives a bilateral retinal projection. This region is assumed to be homologous with the IGL described in other mammals. Cells containing L-ENK-IR are distributed throughout the LGN in groups that overlap, but which have a distinctly different distribution than the more extensive groups of NPY-IR cells.

Animals↗

PubMed1991

Lateral hypothalamic regulation of circadian rhythm phase.

The suprachiasmatic nuclei generate a circadian rhythm which can be described by period, phase and amplitude variables. Evidence is accumulating that the three descriptors of circadian rhythmicity can be modulated independently by several brain structures. This report describes the effects of lateral hypothalamic (LHA) damage on control of period, phase and amplitude of the hamster locomotor rhythm. Adult male hamsters received bilateral electrolytic lesions of the far lateral LHA. These lesions had no effect on the circadian period in constant dim, but significantly advanced the onset of nocturnal wheel running and lengthened the duration of the activity phase. Rate of reentrainment after a 6-h phase advance or delay was not affected by the lesion. Rhythm amplitude, as indicated by the number of wheel revolutions per day, was not affected by the lesions. The results support the view that different brain regions can exert independent modulatory control over the basic circadian rhythm generated by the suprachiasmatic nucleus.

Animals↗