Hilmar Meissl

Bio: Hilmar Meissl is an academic researcher from Max Planck Society. The author has contributed to research in topics: Melatonin & Pineal gland. The author has an hindex of 24, co-authored 50 publications receiving 1836 citations. Previous affiliations of Hilmar Meissl include Shizuoka University & Goethe University Frankfurt.

The pineal organ of teleost fishes

Abstract: The pineal organ of teleost fish is a directly photosensory organ that contains photoreceptor cells similar to those of the retina. It conveys photoperiod information to the brain via neural pathways and by release of indoleamines, primarily melatonin, into the circulation. The photoreceptor cells respond to changes in ambient illumination with a gradual modulation of neurotransmission to second-order neurons that innervate various brain centres, and by modulation of indoleamine synthesis. Melatonin is produced rhythmically, and melatonin synthesis may be regulated either directly by ambient photoperiod, or by an endogenous circadian oscillator that is entrained by the photoperiod. During natural conditions, melatonin is produced at highest levels during the night. Although the pineal organ undoubtedly influences a variety of physiological parameters, as assessed by experimental removal of the pineal organ and/or administration of exogenous indoleamines, its role in any physiological situation is not clear cut. The effects of any interference with pineal functions appear to vary with the time of year and experimental photothermal regimes. There are strong indications that the pineal organ is one component in a central neural system that constitutes the photoperiod-responding system of the animal, i.e. the system that is responsible for correct timing of daily and seasonal physiological rhythms. It is important to envisage the pineal organ as a part of this system; it interacts with other photosensory structures (the retina, possibly extraretinal non-pineal photoreceptors) and circadian rhythm generators

Responses of neurones of the rat suprachiasmatic nucleus to retinal illumination under photopic and scotopic conditions

Abstract: The suprachiasmatic nuclei (SCN) of the anterior hypothalamus have been identified as a major pacemaker of the circadian system in mammals. The endogenous circadian rhythmicity of their neural activity can be directly entrained to the environmental light-dark cycle via the retina and the retinohypothalamic tract. Neurophysiological studies using both single-unit and multi-unit recordings have shown that a subpopulation of SCN cells is influenced by retinal illumination (Groos & Mason, 1980) with a responsiveness to changes in both duration and intensity of illumination (Meijer et al. 1986). The identity of the photoreceptor type that mediates the responsiveness of the circadian system of rodents to light remains, however, unknown. Involvement of either a cone opsin-based mechanism (Nelson & Takahashi, 1991) or rhodopsin (Bronstein et al. 1987) has been suggested. An involvement of at least one photoreceptor with cone-like characteristics has been proposed (Provencio & Foster, 1995; David-Gray et al. 1998) and recently the possibility of non-rod, non-cone photoreceptors has also been suggested (Freedman et al. 1997; reviewed by Foster, 1998). A previous study from this laboratory demonstrated an input via both retinal rod and cone pathways to the pineal gland of mammals (Thiele & Meissl, 1987), raising the prospect that more than one photoreceptor may be involved in transmitting a photic signal to the circadian system. In the present study we have examined the spectral sensitivity and other response characteristics of SCN neurones under scotopic and photopic conditions to evaluate the possible mechanisms underlying photoreception in the circadian system. Recently, a novel cone photopigment has been identified using immunohistochemical methods (Szel & Rohlich, 1992). From electroretinographic recordings it appears that it has a maximal sensitivity in the near ultraviolet (UV) part of the spectrum and minimal sensitivity in the ‘visible’ part (Deegan & Jacobs, 1993). Whether this photopigment is used in visual processing remains unclear. It may have a local homeostatic function in the retina and may not necessarily be involved in the transmission of visual signals to brain centres. In that case, central neurones should show no spectral sensitivity changes in response to short wavelength (SW) or long wavelength (LW) chromatic adaptation. Therefore, an additional aim of this study was to determine whether SCN neurones had any unusual properties in the ultraviolet range that might indicate that the novel SW photopigment is used in higher visual processes.

Evolution of photosensory pineal organs in new light: the fate of neuroendocrine photoreceptors

Abstract: Pineal evolution is envisaged as a gradual transformation of pinealocytes (a gradual regression of pinealocyte sensory capacity within a particular cell line), the so-called sensory cell line of the pineal organ. In most non-mammals the pineal organ is a directly photosensory organ, while the pineal organ of mammals (epiphysis cerebri) is a non-sensory neuroendocrine organ under photoperiod control. The phylogenetic transformation of the pineal organ is reflected in the morphology and physiology of the main parenchymal cell type, the pinealocyte. In anamniotes, pinealocytes with retinal cone photoreceptor-like characteristics predominate, whereas in sauropsids so-called rudimentary photoreceptors predominate. These have well-developed secretory characteristics, and have been interpreted as intermediaries between the anamniote pineal photoreceptors and the mammalian non-sensory pinealocytes. We have re-examined the original studies on which the gradual transformation hypothesis of pineal evolution is based, and found that the evidence for this model of pineal evolution is ambiguous. In the light of recent advances in the understanding of neural development mechanisms, we propose a new hypothesis of pineal evolution, in which the old notion 'gradual regression within the sensory cell line' should be replaced with 'changes in fate restriction within the neural lineage of the pineal field'.

Suprachiasmatic Nuclei Grafts Restore the Circadian Rhythm in the Paraventricular Nucleus of the Hypothalamus

Abstract: The mammalian suprachiasmatic nucleus (SCN) controls the circadian rhythm of many physiological and behavioral events by an orchestrated output of the electrical activity of SCN neurons. We examined the propagation of output signals from the SCN into the hypothalamus, especially into the region of the paraventricular nucleus, through multimicroelectrode recordings using acute and organotypic brain slices. Circadian rhythms in spontaneous firing rate with a period close to 24 hr were demonstrated in the SCN, in directly adjacent hypothalamic regions, and in the region of the paraventricular nucleus of the hypothalamus, an important center for the integration of neuroendocrine, homeostatic, and autonomic functions. The activity rhythms recorded from structures outside of the SCN were in phase with the rhythms in the SCN. Cyclic information in the hypothalamus was lost after ablation of the SCN but could be restored by SCN grafts, indicating that a humoral factor is responsible for the restoration of circadian rhythmicity in the absence of neural connections. Periodic application of arginine-vasopressin (AVP) provided evidence that AVP can induce rhythmicity in the hypothalamus. These data indicate that the SCN uses a dual (neuronal and humoral) mechanism for communication with its targets in the brain.

The photosensory function of the pineal organ of the pike (Esox lucius L.) Correlation between structure and function

Abstract: Electrical recordings from the exposed pineal organ of the pike (Esox lucius L.) were performed in order to localize the photoreceptive structures. Extracellular recordings showed a maintained activity of nerve fibers from the pineal tract and of single neurons from the distal region of the pineal organ. At increasing levels of steady exposure to white light, the impulse frequency decreased. Illumination of the organ with wavelengths between 380 and 710 nm resulted in an inhibition of the spike activity (achromatic response), associated with slow graded responses (electropinealogram, EPG). Sensitivity curves exhibited maxima at 530 and 620 nm in the light adapted, and one maximum at 530 nm in the dark adapted organ. In rare occasions, inhibitory (λmax 380 nm) and excitatory (λmax 620 nm) responses were recorded from single ganglion cells (chromatic response). Some observations (dark adaptation curves; intensity-duration relationship) suggest that the spike potentials and graded responses are probably not generated by the same structures. Moreover, slow potentials without spike potentials were recorded from isolated medial regions of the pineal where no nerve cells are observed. The pineal organ of the pike appears to be a functional photoreceptive organ that may act as a dosimeter of solar radiation, and as an indicator of day-length. The morphological differentiation of its epithelium is closely related to its function, no electrical activity being propagated from the medial region to the brain.

Phototransduction by retinal ganglion cells that set the circadian clock.

Abstract: Light synchronizes mammalian circadian rhythms with environmental time by modulating retinal input to the circadian pacemaker-the suprachiasmatic nucleus (SCN) of the hypothalamus. Such photic entrainment requires neither rods nor cones, the only known retinal photoreceptors. Here, we show that retinal ganglion cells innervating the SCN are intrinsically photosensitive. Unlike other ganglion cells, they depolarized in response to light even when all synaptic input from rods and cones was blocked. The sensitivity, spectral tuning, and slow kinetics of this light response matched those of the photic entrainment mechanism, suggesting that these ganglion cells may be the primary photoreceptors for this system.

Melanopsin-Containing Retinal Ganglion Cells: Architecture, Projections, and Intrinsic Photosensitivity

Abstract: The primary circadian pacemaker, in the suprachiasmatic nucleus (SCN) of the mammalian brain, is photoentrained by light signals from the eyes through the retinohypothalamic tract. Retinal rod and cone cells are not required for photoentrainment. Recent evidence suggests that the entraining photoreceptors are retinal ganglion cells (RGCs) that project to the SCN. The visual pigment for this photoreceptor may be melanopsin, an opsin-like protein whose coding messenger RNA is found in a subset of mammalian RGCs. By cloning rat melanopsin and generating specific antibodies, we show that melanopsin is present in cell bodies, dendrites, and proximal axonal segments of a subset of rat RGCs. In mice heterozygous for tau-lacZ targeted to the melanopsin gene locus, beta-galactosidase-positive RGC axons projected to the SCN and other brain nuclei involved in circadian photoentrainment or the pupillary light reflex. Rat RGCs that exhibited intrinsic photosensitivity invariably expressed melanopsin. Hence, melanopsin is most likely the visual pigment of phototransducing RGCs that set the circadian clock and initiate other non-image-forming visual functions.

The mammalian circadian timing system: organization and coordination of central and peripheral clocks.

Abstract: Most physiology and behavior of mammalian organisms follow daily oscillations. These rhythmic processes are governed by environmental cues (e.g., fluctuations in light intensity and temperature), an internal circadian timing system, and the interaction between this timekeeping system and environmental signals. In mammals, the circadian timekeeping system has a complex architecture, composed of a central pacemaker in the brain's suprachiasmatic nuclei (SCN) and subsidiary clocks in nearly every body cell. The central clock is synchronized to geophysical time mainly via photic cues perceived by the retina and transmitted by electrical signals to SCN neurons. In turn, the SCN influences circadian physiology and behavior via neuronal and humoral cues and via the synchronization of local oscillators that are operative in the cells of most organs and tissues. Thus, some of the SCN output pathways serve as input pathways for peripheral tissues. Here we discuss knowledge acquired during the past few years on the complex structure and function of the mammalian circadian timing system.

Action Spectrum for Melatonin Regulation in Humans: Evidence for a Novel Circadian Photoreceptor

Abstract: The photopigment in the human eye that transduces light for circadian and neuroendocrine regulation, is unknown. The aim of this study was to establish an action spectrum for light-induced melatonin suppression that could help elucidate the ocular photoreceptor system for regulating the human pineal gland. Subjects (37 females, 35 males, mean age of 24.5 +/- 0.3 years) were healthy and had normal color vision. Full-field, monochromatic light exposures took place between 2:00 and 3:30 A.M. while subjects' pupils were dilated. Blood samples collected before and after light exposures were quantified for melatonin. Each subject was tested with at least seven different irradiances of one wavelength with a minimum of 1 week between each nighttime exposure. Nighttime melatonin suppression tests (n = 627) were completed with wavelengths from 420 to 600 nm. The data were fit to eight univariant, sigmoidal fluence-response curves (R(2) = 0.81-0.95). The action spectrum constructed from these data fit an opsin template (R(2) = 0.91), which identifies 446-477 nm as the most potent wavelength region providing circadian input for regulating melatonin secretion. The results suggest that, in humans, a single photopigment may be primarily responsible for melatonin suppression, and its peak absorbance appears to be distinct from that of rod and cone cell photopigments for vision. The data also suggest that this new photopigment is retinaldehyde based. These findings suggest that there is a novel opsin photopigment in the human eye that mediates circadian photoreception.