Specificity of Circadian Function Suprachiasmatic Nucleus

Total Page:16

File Type:pdf, Size:1020Kb

Specificity of Circadian Function Suprachiasmatic Nucleus The Journal of Neuroscience, August 1989. g(8): 2671-2677 Specificity of Circadian Function Transplants of the Fetal Suprachiasmatic Nucleus David J. Earnest, Celia D. Sladek, Don M. Gash, and Stanley J. Wiegand Department of Neurobiology and Anatomy, University of Rochester School of Medicine, Rochester, New York 14642 Fetal tissues obtained from specific regions of the develop- and locomotor activity (Drucker-Colin et al., 1984; DeCoursey ing hypothalamus were transplanted to determine wheth- and Buggy, 1986; Lehman et al., 1987). However, little is known er the precursor neurons of the suprachiasmatic nucleus about the mechanismsby which thesetransplants restore rhyth- (SCN) can be distinguished from those of the presumptive micity. One possibility is that the grafted neuronsrestore rhyth- paraventricular nucleus (PVN) on the basis of the functional micity by providing a specific trophic factor(s) which induces capacity to generate circadian rhythms. The presumptive plasticity in the neural organization of the circadian systemand SCN, the PVN, and a portion of the neocortical primordium enablesother neurons in the host brain to assumethis time- were dissected from the developing forebrains of normal keepingfunction in the absenceofthe in situ SCN. Alternatively, Long-Evans fetuses, separated, and selectively transplant- the transplanted hypothalamic neurons may intrinsically func- ed into the periventricular-third ventricle region of adult, tion as a circadian pacemakerand restore rhythmicity in SCN- vasopressin (VP)-deficient Srattleboro rats. In host animals lesioned hosts through neurohumoral signalsand/or the estab- that received grafts containing the precursor population of lishment of neuralconnections with the host brain. In this regard, SCN neurons, the temporal profile of VP levels in the cere- if the transplanted neuronsare functioning as a circadian pace- brospinal fluid (CSF) oscillated with a circadian periodicity maker, then endogenousbiological activities cxpresscdby these in a manner similar to that observed in normal Long-Evans neurons should oscillate with a circadian periodicity. This hy- rats. CSF collected serially from animals with grafts of the pothesis is basedon observations that indices of SCN activity presumptive PVN also contained VP, but no circadian vari- such as neuronal firing rate and secretory activity oscillate in a ation was manifested in peptide levels. VP was undetectable circadian fashion and that the oscillatory nature of these activ- in CSF samples obtained from Srattleboro rats with cortical ities is an endogenousfeature of SCN neurons (Green and Gil- grafts. In association with their circadian functional capacity, lette, 1982; Inouyc and Kawamura, 1982; Earnest and Sladek, grafts of the SCN primordium were characterized by clusters 1987; Gillette and Reppert, 1987). Consequently, the present of parvicellular neurons immunopositive for VP or vasoactive investigation was conducted to determine whether grafts of the intestinal polypeptide (VIP) that resembled the cell groups primordial SCN develop the distinctive capacity to function as of the in situSCN. In contrast, transplants of the presumptive a circadian clock. PVN did not contain neurons immunoreactive for VIP, and Since the circadian patterns of vasopressin (VP) secretion the VP neurons in these grafts resembled the neurosecretory observed in vivo and in vitro (Schwartz and Reppert, 1985; cells of the PVN. These results demonstrate that grafts con- Earnest and Sladek, 1987; Gillette and Reppert, 1987) appear taining VP neurons derived from the primordial SCN develop to directly reflect the intrinsic activity ofa prominent population not only the cytological and neurochemical features which of VP neurons located in the SCN (Vandesandeet al., 1975; distinguish this population from the VP neurons of the PVN Moore, 1983), the presentstudy utilized VP releaseas an index in situ but also the unique functional capacity of a circadian of the activity of transplanted SCN neurons. Experiments were pacemaker to generate endogenous rhythms in secretory designedto determine whether grafts containing the precursor activity. populations of SCN neuronsdevelop the capacity to releaseVP into the cerebrospinalfluid (CSF’) in a circadian fashion. Brat- The suprachiasmatic nucleus (SCN) of the hypothalamus is an tleboro rats were utilized as transplant recipients becausethe integral neural locus for the generation of circadian rhythms in genetic deficiency in brain VP in this strain (Sokol et al., 1976) mammals. Recent applications of the neural transplantation allows unequivocal identification of vasopressinergicneural technique to the study of the mammalian circadian organization processesand VP in the CSF asemanating from grafts of normal have served to corroborate evidence for this function of the tissue. SCN. Specifically, transplants of fetal hypothalamus containing Based on reports indicating that grafts of the fetal anterior the SCN have been reported to restore circadian rhythms in hypothalamus frequently contain 2 or more cytologically dis- behavioral activities of SCN-lesioned hosts, such as drinking tinct populations of VP neurons that resemblethe normal com- plements found in the in situ paraventricular, supraoptic and suprachiasmaticnuclei (Boer et al., 1985; Wiegand and Gash, Received July 29, 1988; revised Nov. 8, 1988; accepted Jan. 18, 1989. 1987, 1988a), this study was designedto provide for the trans- Correspondence should be addressed IO David J. Earnest, Department of Neu- robiology and Anatomy, University of Rochester School of Medicine, 601 Elm- plantation of a more homogeneouspopulation of SCN-like VP wood Ave., Rochester, NY 14642. neurons. Our approach entailed the selective transplantation of Copyright 0 1989 Society for Neuroscience 0270-6474/89/082671-07$02.00/O topographically discrete regionsof the developing hypothalamus 2672 Earnest et al. - Circadian Activity of Transplanted Suprachiasmatic Neurons containing the anlagen of either the SCN or paraventricular at least 2 times greater than the nadir value for the cycle. Using this nucleus (PVN; Altman and Bayer, 1978a, b) so as to evaluate phase reference point, the time interval between consecutive reference points was measured so as to determine period length and, ultimately, specificity in the capacity of the grafts to generate circadian VP whether the peak in CSF VP recurred with a circadian periodicity. rhythms. The relationship between the functional capacities and Statistical analvsis was oerformed on the means for VP levels usina a the snecific cvtoloaical and immunohistochemical features of one-way analysis of valance with repeated measures to determine Lhe grafts was also evaluated. significance of sampling time. Group means in this analysis were ob- tained by arbitrarily aligning the highest value for CSF VP in individual animals because the individual profiles expressed bv SCN (or PVN) Materials and Methods grafts were not phase-coordinated with each other. Differences in VP levels between sampling intervals within a given circadian day were Animals and housing conditions. Young adult male rats of the Brattle- tested post hoc for significance using the Newman-Keuls sequential boro strain (Blue Spruce Farms), homozygous for diabetes insipidus, range test. were utilized as transplant recipients. Age-matched male Long-Evans Histological procedures. Following the completion of CSF sampling, rats (Charles Rivers Laboratories) served as nontransplanted controls. animals were killed with a lethal dose of sodium uentobarbital and Throughout this study, experimental and control animals were housed perfused with fixative solution (4% paraformaldehyhe or 2% parafor- individually and maintained in a temperature-controlled environment maldehyde and 0.1% glutaraldehyde), and the brains were sectioned and (21°C) with food and water provided ad libitum. Except where noted prepared for immunohistochemical processing as described previously otherwise, the animals were exposed to a 12-hr: 12-hr light-dark cycle (Watson et al., 1986). A few of the animals with neural grafts were (lights on 06.00 to 18.00). Donor tissue of known gestational age was perfused and subsequently injected with opaque gelatin-ink solutions obtained from the fetuses of Long-Evans females (Charles Rivers Lab- for the visualization of microvasculature (Wiegand and Gash, 1988a). oratories) that had been bred with males of the same strain. The preg- A l-in-6 series of 30-wrn sections was processed for localization of nancies were timed by considering the morning of sperm detection in arginine VP. Additional series were processed for localization of va- the vaginal lavage as day 0 of gestation. soactive intestinal polypeptide (VIP) or were stained with thionin. The Preparation and transplantation ofdonor tissue. Fetuses were removed remaining series of sections were reserved for further immunohisto- from Long-Evans dams, killed on days 15, 16, or 17 of gestation and chemical analysis. Peptides were detected by means of an avidin-biotin placed in an ice-cold chamber moistened with Eagle’s medium. The immunoperoxidase procedure (Watson et al., 1986; Wiegand and Gash, fetal brain was removed and a coronal section containing the anterior 1988b). The primary antiseraagainst VP (ICN Immunobiologicals)and hypothalamus was obtained by making incisions just anterior to the VIP (ICN Immunobiologicals) were raised in rabbits and used at di- optic chiasm and at the midpoint between the chiasm and the developing
Recommended publications
  • The Superior Colliculus–Pretectum Mediates the Direct Effects of Light on Sleep
    Proc. Natl. Acad. Sci. USA Vol. 95, pp. 8957–8962, July 1998 Neurobiology The superior colliculus–pretectum mediates the direct effects of light on sleep ANN M. MILLER*, WILLIAM H. OBERMEYER†,MARY BEHAN‡, AND RUTH M. BENCA†§ *Neuroscience Training Program and †Department of Psychiatry, University of Wisconsin–Madison, 6001 Research Park Boulevard, Madison, WI 53719; and ‡Department of Comparative Biosciences, University of Wisconsin–Madison, Room 3466, Veterinary Medicine Building, 2015 Linden Drive West, Madison, WI 53706 Communicated by James M. Sprague, The University of Pennsylvania School of Medicine, Philadelphia, PA, May 27, 1998 (received for review August 26, 1997) ABSTRACT Light and dark have immediate effects on greater REM sleep expression occurring in light rather than sleep and wakefulness in mammals, but the neural mecha- dark periods (8, 9). nisms underlying these effects are poorly understood. Lesions Another behavioral response of nocturnal rodents to of the visual cortex or the superior colliculus–pretectal area changes in lighting conditions consists of increased amounts of were performed in albino rats to determine retinorecipient non-REM (NREM) sleep and total sleep after lights-on and areas that mediate the effects of light on behavior, including increased wakefulness following lights-off (4). None of the rapid eye movement sleep triggering by lights-off and redis- light-induced behaviors (i.e., REM sleep, NREM sleep, or tribution of non-rapid eye movement sleep in short light–dark waking responses to lighting changes) appears to be under cycles. Acute responses to changes in light conditions were primary circadian control: the behaviors are not eliminated by virtually eliminated by superior colliculus-pretectal area le- destruction of the suprachiasmatic nucleus (24) and can be sions but not by visual cortex lesions.
    [Show full text]
  • Molecular and Cellular Networks in the Suprachiasmatic Nuclei
    International Journal of Molecular Sciences Review Molecular and Cellular Networks in The Suprachiasmatic Nuclei Lama El Cheikh Hussein, Patrice Mollard and Xavier Bonnefont * Institut de Génomique Fonctionnelle (IGF), University Montpellier, CNRS, INSERM, 34094 Montpellier, France; [email protected] (L.E.C.H.); [email protected] (P.M.) * Correspondence: [email protected]; Tel.: +33-4-3435-9306 Received: 1 April 2019; Accepted: 23 April 2019; Published: 25 April 2019 Abstract: Why do we experience the ailments of jetlag when we travel across time zones? Why is working night-shifts so detrimental to our health? In other words, why can’t we readily choose and stick to non-24 h rhythms? Actually, our daily behavior and physiology do not simply result from the passive reaction of our organism to the external cycle of days and nights. Instead, an internal clock drives the variations in our bodily functions with a period close to 24 h, which is supposed to enhance fitness to regular and predictable changes of our natural environment. This so-called circadian clock relies on a molecular mechanism that generates rhythmicity in virtually all of our cells. However, the robustness of the circadian clock and its resilience to phase shifts emerge from the interaction between cell-autonomous oscillators within the suprachiasmatic nuclei (SCN) of the hypothalamus. Thus, managing jetlag and other circadian disorders will undoubtedly require extensive knowledge of the functional organization of SCN cell networks. Here, we review the molecular and cellular principles of circadian timekeeping, and their integration in the multi-cellular complexity of the SCN.
    [Show full text]
  • Cholinergic Regulation of the Suprachiasmatic Nucleus Circadian Rhythm Via a Muscarinic Mechanism at Night
    The Journal of Neuroscience, January 15, 1996, 16(2):744-751 Cholinergic Regulation of the Suprachiasmatic Nucleus Circadian Rhythm via a Muscarinic Mechanism at Night Chen Liul and Martha U. Gillette’,2,3 1Neuroscience Program, and Departments of 2Cell and Structural Biology and 3Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 6 180 I In mammals, the suprachiasmatic nucleus (SCN) is responsible for agonists, muscarine and McN-A-343 (Ml-selective), but not by the generation of most circadian rhythms and for their entrainment nicotine. Furthermore, the effect of carbachol was blocked by the to environmental cues. Carbachol, an agonist of acetylcholine mAChR antagonist atropine (0.1 PM), not by two nicotinic antag- (ACh), has been shown to shift the phase of circadian rhythms in onists, dihydro-6-erythroidine (10 PM) and d-tubocurarine (10 PM). rodents when injected intracerebroventricularly. However, the site The Ml -selective mAChR antagonist pirenzepine completely and receptor type mediating this action have been unknown. In blocked the carbachol effect at 1 PM, whereas an M3-selective the present experiments, we used the hypothalamic brain-slice antagonist, 4,2-(4,4’-diacetoxydiphenylmethyl)pyridine, partially technique to study the regulation of the SCN circadian rhythm of blocked the effect at the same concentration. These results dem- neuronal firing rate by cholinergic agonists and to identify the onstrate that carbachol acts directly on the SCN to reset the receptor subtypes involved. We found that the phase of the os- phase of its firing rhythm during the subjective night via an Ml -like cillation in SCN neuronal activity was reset by a 5 min treatment mAChR.
    [Show full text]
  • Suprachiasmatic Modulation of Noradrenaline Release in the Ventrolateral Preoptic Nucleus
    6412 • The Journal of Neuroscience, June 13, 2007 • 27(24):6412–6416 Brief Communications Suprachiasmatic Modulation of Noradrenaline Release in the Ventrolateral Preoptic Nucleus Benoıˆt Saint-Mleux,1 Laurence Bayer,1 Emmanuel Eggermann,1 Barbara E. Jones,2 Michel Mu¨hlethaler,1 and Mauro Serafin1 1De´partement de Neurosciences Fondamentales, Centre Me´dical Universitaire, 1211 Gene`ve 4, Switzerland, and 2Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4 As the major brain circadian pacemaker, the suprachiasmatic nucleus (SCN) is known to influence the timing of sleep and waking. We thus investigated here the effect of SCN stimulation on neurons of the ventrolateral preoptic nucleus (VLPO) thought to be involved in promoting sleep. Using an acute in vitro preparation of the rat anterior hypothalamus/preoptic area, we found that whereas single-pulse stimulations of the SCN evoked standard fast ionotropic IPSPs and EPSPs, train stimulations unexpectedly evoked a long-lasting inhi- bition (LLI). Such LLIs could also be evoked in VLPO neurons by pressure application of NMDA within the SCN, indicating the specific activation of SCN neurons. This LLI was shown to result from the presynaptic facilitation of noradrenaline release, because it was ␣ suppressed in presence of yohimbine, a selective antagonist of 2-adrenoreceptors. The LLI depended on the opening of a potassium conductance, because it was annulled at EK and could be reversed below EK. These results show that the SCN can provide an LLI of the sleep-promoting VLPO neurons that could play a role in the circadian organization of the sleep–waking cycle.
    [Show full text]
  • Retinal Afferents to the Dorsal Raphe Nucleus in Rats and Mongolian Gerbils
    THE JOURNAL OF COMPARATIVE NEUROLOGY 414:469–484 (1999) Retinal Afferents to the Dorsal Raphe Nucleus in Rats and Mongolian Gerbils KATHERINE V. FITE,1* SKIRMANTAS JANUSˇ ONIS,1 WARREN FOOTE,2 AND LYNN BENGSTON1 1Neuroscience and Behavior Program, University of Massachusetts, Amherst, Massachusetts 01003 2Massachusetts General Hospital, Boston, Massachusetts 02114 ABSTRACT A direct pathway from the retina to the dorsal raphe nucleus (DRN) has been demonstrated in both albino rats and Mongolian gerbils. Following intraocular injection of cholera toxin subunit B (CTB), a diffuse stream of CTB-positive, fine-caliber optic axons emerged from the optic tract at the level of the pretectum/anterior mesencephalon. In gerbils, CTB-positive axons descended ventromedially into the periaqueductal gray, moving caudally and arborizing extensively throughout the DRN. In rats, the retinal-DRN projection com- prised fewer, but larger caliber, axons, which arborized in a relatively restricted region of the lateral and ventral DRN. Following injection of CTB into the lateral DRN, retrogradely labeled ganglion cells (GCs) were observed in whole-mount retinas of both species. In gerbils, CTB-positive GCs were distributed over the entire retina, and a nearest-neighbor analysis of CTB-positive GCs showed significant regularity (nonrandomness) in their distribution. The overall distribution of gerbil GC soma diameters ranged from 8 to 22 µm and was skewed slightly towards the larger soma diameters. Based on an adaptive mixtures model statistical analysis, two Gaussian distributions appeared to comprise the total GC distribution, with mean soma diameters of 13 (SEM Ϯ1.7) µm, and 17 (SEM Ϯ1.5) µm, respectively. In rats, many fewer CTB-positive GCs were labeled following CTB injections into the lateral DRN, and nearly all occurred in the inferior retina.
    [Show full text]
  • Role of the Suprachiasmatic Nucleus
    Brain Research Reviews 49 (2005) 429–454 www.elsevier.com/locate/brainresrev Review Circadian regulation of sleep in mammals: Role of the suprachiasmatic nucleus Ralph E. MistlbergerT Department of Psychology, Simon Fraser University, 8888 University Drive, Burnaby, Canada BC V5A 1S6 Accepted 7 January 2005 Available online 8 March 2005 Abstract Despite significant progress in elucidating the molecular basis for circadian oscillations, the neural mechanisms by which the circadian clock organizes daily rhythms of behavioral state in mammals remain poorly understood. The objective of this review is to critically evaluate a conceptual model that views sleep expression as the outcome of opponent processes—a circadian clock-dependent alerting process that opposes sleep during the daily wake period, and a homeostatic process by which sleep drive builds during waking and is dissipated during sleep after circadian alerting declines. This model is based primarily on the evidence that in a diurnal primate, the squirrel monkey (Saimiri sciureus), ablation of the master circadian clock (the suprachiasmatic nucleus; SCN) induces a significant expansion of total daily sleep duration and a reduction in sleep latency in the dark. According to this model, the circadian clock actively promotes wake but only passively gates sleep; thus, loss of circadian clock alerting by SCN ablation impairs the ability to sustain wakefulness and causes sleep to expand. For comparison, two additional conceptual models are described, one in which the circadian clock actively promotes sleep but not wake, and a third in which the circadian clock actively promotes both sleep and wake, at different circadian phases. Sleep in intact and SCN-damaged rodents and humans is first reviewed, to determine how well the data fit these conceptual models.
    [Show full text]
  • The Role of the Intergeniculate Leaflet in Entrainment of Circadian
    The Journal of Neuroscience, January 1, 1999, 19(1):372–380 The Role of the Intergeniculate Leaflet in Entrainment of Circadian Rhythms to a Skeleton Photoperiod Kim Edelstein and Shimon Amir Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, Montreal, Quebec, Canada H3G 1M8 Mammalian circadian rhythms are synchronized to environmen- by 12 hr of darkness, but exhibited free-running rhythms when tal light/dark (LD) cycles via daily phase resetting of the circa- housed under an SPP consisting of two 1 hr light pulses given dian clock in the suprachiasmatic nucleus (SCN). Photic infor- at times corresponding to dusk and dawn. Despite IGL lesions mation is transmitted to the SCN directly from the retina via the and other damage to the visual system, the SCN displayed retinohypothalamic tract (RHT) and indirectly from the retinore- normal sensitivity to the entraining light, as assessed by light- cipient intergeniculate leaflet (IGL) via the geniculohypotha- induced Fos immunoreactivity. In addition, all IGL-lesioned, lamic tract (GHT). The RHT is thought to be both necessary and free-running rats showed masking of the body temperature sufficient for photic entrainment to standard laboratory light/ rhythm during the SPP light pulses. These results show that the dark cycles. An obligatory role for the IGL–GHT in photic en- integrity of the IGL is necessary for entrainment of circadian trainment has not been demonstrated. Here we show that the rhythms to a lighting schedule like that experienced by noctur- IGL is necessary for entrainment of circadian rhythms to a nal rodents in the natural environment.
    [Show full text]
  • No Slide Title
    Laboratory 11: Cartoons Chiyeko Tsuchitani, Ph.D. NOTE: These illustrations are NOT to be reproduced in the public domain For the visually challenged, cartoons that may help you remember some hypothalamic nuclei and limbic structures. You can study the figures and the review questions in Lab 11 of the Laboratory Guide to learn the connections and functions of these structures.. PS #26 For PS24: Two Cows 1. What is the cow at the left eating? 2. What is hanging off the chin of the cow at the left ? 3. What is forming the chin of the cow at the left? 4. What is hanging over the nose of the cow at the left? 5. What is forming the dark nose of the cow at the right? 6. What is forming the chin of the cow at the right? 7. What is forming the hollow “bump” on the forehead of the cow at the right? 8. Is the thalamus present in this picture? 9. Can you locate the supraoptic and suprachiasmatic nuclei? For PS24: Two Cows 1. The anterior commissure 2. The optic chiasm 3. The preoptic nucleus of the hypothalamus 4. The column of the fornix 5. The postcommissural fornix 6. The anterior nucleus of the hypothalamus 7. The terminal vein 8. The thalamus is not present in this picture. 9. The supraoptic nucleus is above the optic tract (right) and suprachiasmatic nucleus is above the optic chiasm. PS #25 For PS25: Armadillo 1. The nose of the armadillo is what structure? 2. What hypothalamic nucleus forms the snout (above the nose) ? 3.
    [Show full text]
  • Diencephalon and Hypothalamus
    Diencephalon and Hypothalamus Objectives: 1) To become familiar with the four major divisions of the diencephalon 2) To understand the major anatomical divisions and functions of the hypothalamus. 3) To appreciate the relationship of the hypothalamus to the pituitary gland Four Subdivisions of the Diencephalon: Epithalamus, Subthalamus Thalamus & Hypothalamus Epithalamus 1. Epithalamus — (“epi” means upon) the most dorsal part of the diencephalon; it forms a caplike covering over the thalamus. a. The smallest and oldest part of the diencephalon b. Composed of: pineal body, habenular nuclei and the caudal commissure c. Function: It is functionally and anatomically linked to the limbic system; implicated in a number of autonomic (ie. respiratory, cardio- vascular), endocrine (thyroid function) and reproductive (mating behavior; responsible for postpartum maternal behavior) functions. Melatonin is secreted by the pineal gland at night and is concerned with biological timing including sleep induction. 2. Subthalamus — (“sub” = below), located ventral to the thalamus and lateral to the hypothalamus (only present in mammals). a. Plays a role in the generation of rhythmic movements b. Recent work indicates that stimulation of the subthalamus in cats inhibits the micturition reflex and thus this nucleus may also be involved in neural control of micturition. c. Stimulation of the subthalamus provides the most effective treatment for late-stage Parkinson’s disease in humans. Subthalamus 3. Thalamus — largest component of the diencephalon a. comprised of a large number of nuclei; -->lateral geniculate (vision) and the medial geniculate (hearing). b. serves as the great sensory receiving area (receives sensory input from all sensory pathways except olfaction) and relays sensory information to the cerebral cortex.
    [Show full text]
  • Projections of the Paraventricular and Paratenial Nuclei of the Dorsal Midline Thalamus in the Rat
    THE JOURNAL OF COMPARATIVE NEUROLOGY 508:212–237 (2008) Projections of the Paraventricular and Paratenial Nuclei of the Dorsal Midline Thalamus in the Rat ROBERT P. VERTES* AND WALTER B. HOOVER Center for Complex Systems and Brain Sciences, Florida Atlantic University, Boca Raton, Florida 33431 ABSTRACT The paraventricular (PV) and paratenial (PT) nuclei are prominent cell groups of the midline thalamus. To our knowledge, only a single early report has examined PV projections and no previous study has comprehensively analyzed PT projections. By using the antero- grade anatomical tracer, Phaseolus vulgaris leucoagglutinin, and the retrograde tracer, FluoroGold, we examined the efferent projections of PV and PT. We showed that the output of PV is virtually directed to a discrete set of limbic forebrain structures, including ‘limbic’ regions of the cortex. These include the infralimbic, prelimbic, dorsal agranular insular, and entorhinal cortices, the ventral subiculum of the hippocampus, dorsal tenia tecta, claustrum, lateral septum, dorsal striatum, nucleus accumbens (core and shell), olfactory tubercle, bed nucleus of stria terminalis (BST), medial, central, cortical, and basal nuclei of amygdala, and the suprachiasmatic, arcuate, and dorsomedial nuclei of the hypothalamus. The posterior PV distributes more heavily than the anterior PV to the dorsal striatum and to the central and basal nuclei of amygdala. PT projections significantly overlap with those of PV, with some important differences. PT distributes less heavily than PV to BST and to the amygdala, but much more densely to the medial prefrontal and entorhinal cortices and to the ventral subiculum of hippocampus. As described herein, PV/PT receive a vast array of afferents from the brainstem, hypothalamus, and limbic forebrain, related to arousal and attentive states of the animal, and would appear to channel that information to structures of the limbic forebrain in the selection of appropriate responses to changing environmental conditions.
    [Show full text]
  • Distinct Iprgc Subpopulations Mediate Light's Acute and Circadian
    RESEARCH ARTICLE Distinct ipRGC subpopulations mediate light’s acute and circadian effects on body temperature and sleep Alan C Rupp1, Michelle Ren2, Cara M Altimus1, Diego C Fernandez1†, Melissa Richardson1, Fred Turek2, Samer Hattar1,3†, Tiffany M Schmidt2* 1Department of Biology, Johns Hopkins University, Baltimore, United States; 2Department of Neurobiology, Northwestern University, Evanston, United States; 3Department of Neuroscience, Johns Hopkins University, Baltimore, United States Abstract The light environment greatly impacts human alertness, mood, and cognition by both acute regulation of physiology and indirect alignment of circadian rhythms. These processes require the melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs), but the relevant downstream brain areas involved remain elusive. ipRGCs project widely in the brain, including to the central circadian pacemaker, the suprachiasmatic nucleus (SCN). Here we show that body temperature and sleep responses to acute light exposure are absent after genetic ablation of all ipRGCs except a subpopulation that projects to the SCN. Furthermore, by chemogenetic activation of the ipRGCs that avoid the SCN, we show that these cells are sufficient for acute changes in body temperature. Our results challenge the idea that the SCN is a major relay for the acute effects of light on non-image forming behaviors and identify the sensory cells that initiate light’s profound effects on body temperature and sleep. *For correspondence: DOI: https://doi.org/10.7554/eLife.44358.001 [email protected] Present address: †National Institute of Mental Health, Introduction Bethesda, United States Many essential functions are influenced by light both indirectly through alignment of circadian Competing interests: The rhythms (photoentrainment) and acutely by a direct mechanism (sometimes referred to as ‘masking’) authors declare that no (Mrosovsky et al., 1999; Altimus et al., 2008; Lupi et al., 2008; Tsai et al., 2009; LeGates et al., competing interests exist.
    [Show full text]
  • Contributions of the Lateral Habenula to Circadian Timekeeping
    Otalora, B. B., & Piggins, H. (2017). Contributions of the lateral habenula to circadian timekeeping. Pharmacology, Biochemistry and Behavior, 162, 46-54. https://doi.org/10.1016/j.pbb.2017.06.007 Publisher's PDF, also known as Version of record License (if available): CC BY Link to published version (if available): 10.1016/j.pbb.2017.06.007 Link to publication record in Explore Bristol Research PDF-document This is the final published version of the article (version of record). It first appeared online via Elsevier at DOI: 10.1016/j.pbb.2017.06.007. Please refer to any applicable terms of use of the publisher. University of Bristol - Explore Bristol Research General rights This document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/red/research-policy/pure/user-guides/ebr-terms/ Pharmacology, Biochemistry and Behavior 162 (2017) 46–54 Contents lists available at ScienceDirect Pharmacology, Biochemistry and Behavior journal homepage: www.elsevier.com/locate/pharmbiochembeh Review Contributions of the lateral habenula to circadian timekeeping MARK ⁎ Beatriz Baño-Otálora, Hugh D. Piggins Faculty of Biology, Medicine and Health, University of Manchester, M13 9PT, UK ARTICLE INFO ABSTRACT Keywords: Over the past 20 years, substantive research has firmly implicated the lateral habenula in myriad neural pro- Lateral habenula cesses including addiction, depression, and sleep. More recently, evidence has emerged suggesting that the Suprachiasmatic lateral habenula is a component of the brain's intrinsic daily or circadian timekeeping system. This system Circadian rhythm centers on the master circadian pacemaker in the suprachiasmatic nuclei of the hypothalamus that is synchro- Clock genes nized to the external world through environmental light information received directly from the eye.
    [Show full text]