Some cortical and subcortical fiber projections to the accessory optic nuclei in the cat

The terminal nuclei of the accessory optic system receive a dense fiber projection from the contralateral retina and have recently been implicated in visuo-vestibular aspects of oculomotor function. The present anatomical study, based on anterograde tracer experiments with³H-labeled amino acids or horseradish peroxidase, provides evidence for a diverse set of non-retinal inputs to the accessory optic nuclei arising in both the neocortex and the brainstem. Corticofugal fiber projections to the terminal nuclei originate in several areas of the visual cortex; those from the medial Clare-Bishop area may be especially dense. Subcortical inputs to the terminal nuclei include fiber projections arising in (a) the pretectal region; (b) the ventral mesencephalon, probably including the substantia nigra; and (c) more dorsal or caudal parts of the mesencephalic reticular formation. The source of the pretectal projection to the terminal nuclei appears to be the nucleus of the optic tract or the underlying posterior pretectal nucleus. Fiber projections from the ventral mesencephalic tegmentum were labeled by injections infiltrating the substantia nigra, but these deposits all involved, at least marginally, either interstitial cells of the transpeduncular limb of the accessory optic tract or the perinigral tegmentum. The part of the midbrain reticular formation giving rise to an accessory optic projection was not precisely delimited, but it appears to lie outside the substantia nigra proper.Although these afferent projections to the accessory optic nuclei appear individually to be much weaker than the input from the contralateral eye, their presence clearly suggests that transmission of visual information through the terminal nuclei may involve a complex modulation of retinal input by non-retinal pathways.     

The accessory optic fiber system of the golden hamster with special reference to retinohypothalamic projection

The hamster accessory optic fiber system has been investigated with the use of de Olmos-Ingram and Fink-Heimer silver methods following the production of unilateral ocular enucleation. It was found that this fiber system consists of both crossed and uncrossed inferior and superior fasciculi. The fibers of the inferior fasciculus (anterior accessory optic tract) run along the medial edge of the cerebral peduncle and terminate within the medial terminal nucleus of the accessory optic system. The fibers of the superior fasciculus (posterior accessory optic tract) leave the main optic tract, pass superficially over the medial geniculate nucleus and the cerebral peduncle; they synapse within the dorsal, the lateral and the medial terminal accessory optic nuclei. The presence of a retinohypothalamic tract could not be confirmed.     

Entrainment of circadian rhythms: Retinofugal pathways and unilateral suprachiasmatic nucleus lesions

The role of retinohypothalamic input to the suprachiasmatic nuclei (SCN) as well as SCN afferents from the ventrolateral geniculate nuclei (LGN_v) in the entrainment of circadian drinking rhythms was investigated in the rat. Bilateral lesions of the LGN_v and the primary optic tracts had no affect on the entrainment of drinking rhythms to a light-dark cycle, the response to a 12 hr phase shift of the light-dark cycle, or on the period of the free-running circadian rhythm in constant light or constant darkness. Unilateral blinding in rats with or without LGN_v lesions retarded the rate of phase shifting by 2 days and decreased the period of the free-running rhythm in constant light. For rats with unilateral SCN lesions, or such lesions combined with either ipsi- or contra-lateral blinding, the rate of re-entrainment was intermediate between intact and unilaterally blinded rats indicating that unilateral SCN lesions partially reversed the effects of unilateral blinding. Unilateral SCN lesions had no effect on the period of the free-running rhythm in constant light or darkness. These results are consistent with the interpretation that the asymmetrical innervation of the two SCN by the RHT in unilaterally blinded rats delays re-entrainment by changing the phase response curve of the circadian system. This change may be mediated by neural connections between the two SCN.     

Interaction between inhibitory pathways to principal cells in the lateral geniculate nucleus of the cat

Summary Inhibitory interactions between interneurones of the lateral geniculate nucleus (LGN) of the cat were studied with an indirect method based on intracellular recordings of synaptic responses in principal cells. Recurrent inhibitory postsynaptic potentials (IPSPs), evoked by antidromic activation of principal cell axons in the visual cortex, were depresse by a preceding stimulation of the optic tract or the visual cortex. Disynaptic feed-forward IPSPs, evoked by optic tract stimulation, were likewise depressed after cortex stimulation. The duration of the depression was in both cases about 100 ms. The effect was not due to conductance changes in the recorded principal cells or to activation of corticogeniculate fibres. The observations indicate that perigeniculate neurones, the recurrent inhibitory interneurones of the LGN, have mutual inhibitory connexions and that they also project to intrageniculate interneurones, the inhibitory cells in the feed-forward pathway to principal cells. These conclusions were supported by intracellular recordings from a few interneurones. No evidence was found for interaction between feed-forward interneurones activated from separate eyes or for a projection from intrageniculate interneurones to perigeniculate cells. The results point to an unexpected similarity in the organization of the recurrent inhibitory system of principal cells in the LGN and of spinal motoneurones. It is suggested that the recurrent system of the LGN serves as a variable gain regulator in analogy with a recently proposed model for the spinal system.     

光照对哺乳类动物生物钟的调节机制

人体结构不仅存在于空间,而且存在于时间中。由于地球每24h自转一周,因此生物体内的各种功能都有明显的24h昼夜节律。在长期生物进化过程中,生物机体内发育分化出一个特殊的器官——生物钟来协调各种不同组织与器官的昼夜节律。人体的生物钟位于下丘脑的视交叉上核。由于体内生物钟是在地球昼夜环境周期性的变化中进化形成的,因此光照是影响生物钟节律最重要的因素。外界环境的光照信息是由一条独特的神经通路。从视网膜直接投射到视交叉上核,称为视网膜．下丘脑束。这条神经通路不同于经典的视觉成像通路,它不参与视觉成像功能。视锥细胞与视杆细胞全都退化的盲人或动物毫无光感,但他们的生物节律仍然受光照调节。这一现象有很重要的临床意义。本文主要讨论光照对哺乳类动物生物钟调节的神经生物学机制。     

PLEIOTROPIC EFFECTS OF CRYPTOCHROMES 1 AND 2 ON FREE-RUNNING AND LIGHT-ENTRAINED MURINE CIRCADIAN RHYTHMS

Cryptochromes function in both light entrainment of circadian rhythms and in a peripheral circadian clock mechanism in Drosophila . Mice have two closely related cryptochrome genes ( mCry1 and mCry2 ). To further understand the roles of mammalian cryptochromes, we bred mice to carry all possible combinations of wild-type and cryptochrome knockout alleles, and tested these mice for free-running and entrained circadian rhythmicity. We find that a single wild-type copy of mCry1 , but not mCry2 , is sufficient for free running circadian rhythmicity; however, these mice show markedly variable free-running periods. Two wild-type copies of either mCry1 or mCry2 are sufficient to establish a stable free-running clock. A subset of mCry1 ? / mCry ? ; mCry2 ? / mCry2 ? mice have a diurnal activity preference, suggesting that cryptochromes function in light-dependent behavioral masking. We also analyzed mice lacking both cryptochromes and carrying the homozygous rd retinal degeneration mutation. These mice have markedly depressed behavioral photoresponses in light-dark conditions, despite having an anatomically intact retinohypothalamic tract and normal expression of melanopsin. These results suggest that, similar to insect cryptochromes, mammalian cryptochromes function pleiotropically in both circadian rhythm generation and in photic entrainment and behavioral responses.     

Pleiotropic effects of cryptochromes 1 and 2 on free-running and light-entrained murine circadian rhythms

Cryptochromes function in both light entrainment of circadian rhythms and in a peripheral circadian clock mechanism in Drosophila. Mice have two closely related cryptochrome genes (mCry1 and mCry2). To further understand the roles of mammalian cryptochromes, we bred mice to carry all possible combinations of wild-type and cryptochrome knockout alleles, and tested these mice for free-running and entrained circadian rhythmicity. We find that a single wild-type copy of mCry1, but not mCry2, is sufficient for free running circadian rhythmicity; however, these mice show markedly variable free-running periods. Two wild-type copies of either mCry1 or mCry2 are sufficient to establish a stable free-running clock. A subset of mCry1-/mCry-; mCry2-/mCry2- mice have a diurnal activity preference, suggesting that cryptochromes function in light-dependent behavioral masking. We also analyzed mice lacking both cryptochromes and carrying the homozygous rd retinal degeneration mutation. These mice have markedly depressed behavioral photoresponses in light-dark conditions, despite having an anatomically intact retinohypothalamic tract and normal expression of melanopsin. These results suggest that, similar to insect cryptochromes, mammalian cryptochromes function pleiotropically in both circadian rhythm generation and in photic entrainment and behavioral responses.     

Involvement of the retinohypothalamic tract in the photic-like effects of the serotonin agonist quipazine in the rat

Light is the major synchronizer of the mammalian circadian pacemaker located in the suprachiasmatic nucleus. Photic information is perceived by the retina and conveyed to the suprachiasmatic nucleus either directly by the retinohypothalamic tract or indirectly by the intergeniculate leaflet and the geniculohypothalamic tract. In addition, serotonin has been shown to affect the suprachiasmatic nucleus by both direct and indirect serotonin projections from the raphe nuclei. Indeed, systemic as well as local administrations of the serotonin agonist quipazine in the region of the suprachiasmatic nucleus mimic the effects of light on the circadian system of rats, i.e. they induce phase-advances of the locomotor activity rhythm as well as c-FOS expression in the suprachiasmatic nucleus during late subjective night. The aim of this study was to localize the site(s) of action mediating those effects. Phase shifts of the locomotor activity rhythm as well as c-FOS expression in the suprachiasmatic nucleus after s.c. injection of quipazine (10 mg/kg) were assessed in Lewis rats, which had received either radio-frequency lesions of the intergeniculate leaflet or infusions of the serotonin neurotoxin 5,7-dihydroxytryptamine into the suprachiasmatic nucleus (25 microg) or bilateral enucleation. Lesions of intergeniculate leaflet and serotonin afferents to the suprachiasmatic nucleus did not reduce the photic-like effects of quipazine, whereas bilateral enucleation and the subsequent degeneration of the retinohypothalamic tract abolished both the phase-shifting and the FOS-inducing effects of quipazine. The results indicate that photic-like effects of quipazine are mediated via the retinohypothalamic tract.     

Central visual pathways and the distribution of sleep in 24-hr and 1-hr light-dark cycles

The role of the central visual pathways in determining the distribution of sleep in light-dark (LD) cycles in the circadian and ultradian range was examined. EEG, EMG, and brain temperature were recorded under 24-hr (LD 12:12 or LD 10:14) and 1-hr (LD 0.5:0.5) cycles in rats which received either (1) no lesion, (2) primary optic tract lesions, (3) lesions of dorsal and lateral terminal nuclei of the accessory optic system, (4) lesions of medial terminal nucleus of the accessory optic system, or (5) retinohypothalamic tract-suprachiasmatic nucleus lesions. Under 24-hr cycles, about 40% of sleep occurred in the dark in intact rats. Retinohypothalamic tract-suprachiasmatic nucleus lesions abolished this entrainment of sleep to the LD cycle. Under 1-hr cycles, 90% of REM sleep occurred in the dark periods in intact rats. While primary optic tract lesions attenuated this response, it was not completely abolished by any of the visual system lesions. The characteristic LD distributions of sleep in circadian and ultradian cycles may therefore be under separate neural control by the central visual system.     

Development of retinohypothalamic projections in the chick embryo

The retinal projection to the hypothalamus was investigated in embryonic as well as hatched chick using wheat germ agglutinin-conjugated horseradish peroxidase as an anterograde tracer. The presence of an aggregation of anterogradely labeled terminals in the hypothalamus was used to identify the suprachiasmatic nucleus (SCN).

The first clear labeling of retinal fibers in the SCN was found on embryonic day 16, whereas labeling was found in the other primary visual projections, in the diencephalon and mesencephalon, several days earlier. Thus, the retinohypothalamic projection is the last primary visual pathway to develop in the chick embryo.     

Effects of nucleus prepositus hypoglossi lesions on visual climbing fiber activity in the rabbit flocculus

The caudal dorsal cap (dc) of the inferior olive is involved in the control of horizontal compensatory eye movements. It provides those climbing fibers to the vestibulocerebellum that modulate optimally to optokinetic stimulation about the vertical axis. This modulation is mediated at least in part via an excitatory input to the caudal dc from the pretectal nucleus of the optic tract and the dorsal terminal nucleus of the accessory optic system. In addition, the caudal dc receives a substantial GABAergic input from the nucleus prepositus hypoglossi (NPH). To investigate the possible contribution of this bilateral inhibitory projection to the visual responsiveness of caudal dc neurons, we recorded the climbing fiber activity (i.e., complex spikes) of vertical axis Purkinje cells in the flocculus of anesthetized rabbits before and after ablative lesions of the NPH. When the NPH ipsilateral to the recorded flocculus was lesioned, the spontaneous complex spike firing frequency did not change significantly; but when both NPHs were lesioned, the spontaneous complex spike firing frequency increased significantly. When only the contralateral NPH was lesioned, the spontaneous complex spike firing frequency decreased significantly. Neither unilateral nor bilateral lesions had a significant influence on the depth of complex spike modulation during constant velocity optokinetic stimulation or on the transient continuation of complex spike modulation that occurred when the constant velocity optokinetic stimulation stopped. The effects of the lesions on the spontaneous complex spike firing frequency could not be explained when only the projections from the NPH to the inferior olive were considered. Therefore we investigated at the electron microscopic level the nature of the commissural connection between the two NPHs. The terminals of this projection were found to be predominantly GABAergic and to terminate in part on GABAergic neurons. When this inhibitory commissural connection is taken into consideration, then the effects of NPH lesions on the spontaneous firing frequency of floccular complex spikes are qualitatively explicable in terms of relative weighting of the commissural and caudal dc projections of the NPH. In summary, we conclude that in the anesthetized rabbit the inhibitory projection of the NPH to the caudal dc influences the spontaneous firing frequency of floccular complex spikes but not their modulation by optokinetic stimulation.     

Entrainment of circadian rhythm to a photoperiod reversal shows retinal dystrophy in RPE65(-/-) mice

Light entrainment of circadian rhythms is mediated by classical "visual" photoreceptors (rods and cones) as well as "nonvisual" photoreceptive elements (light-detecting cells that do not contribute to classical "vision"). This paper aimed to assess whether light entrainment of locomotor circadian rhythms in mice with impaired rods and cones differs from normal controls and whether this technique, alongside existing techniques, could be used to assess visual function. The study was primarily interested in differences between the entrainment of circadian rhythms of normal-sighted C57Bl/6J mouse and the C57Bl/RPE65 knockout mouse (RPE65(-/-)), although C3H/HeJ (rd/rd) mice were included as a preexisting model of retinal degeneration. Circadian rhythms of motor activity before and after a 12-h light reversal were assessed in custom-built cages that continuously monitored movement. The controls showed a significantly higher mesor and amplitude when compared to the RPE65(-/-) and rd/rd mice. Despite the loss of rods and cones, the RPE65(-/-) and rd/rd maintained a 24-h circadian rhythm entrained to light similar to controls and were capable of circadian reentrainment to a 12-h light reversal. Importantly, this light reentrainment of the circadian phase occurred at a significantly slower rate in the retinal degenerate models than in the controls. The RPE65(-/-) model demonstrates a retinal degenerate reentrainment phenotype when compared to the rd/rd model. It is suggested that these retinal degenerate mice retain the ability to detect light for the purposes of circadian rhythm entrainment. However, alterations of specific parameters of the circadian rhythm with loss of rods and cones may provide measures of loss of visual function (sight).     

Maternal entrainment in the circadian activity rhythm of laboratory mouse (C57BL/6J)

Maternal entrainment of circadian activity rhythm was studied in the laboratory mouse (C57BL/6J). Pregnant mice gave birth in constant dim light and the mother raised the pups until Postnatal Day 18 (weaning). The wheel running activity of these pups was individually monitored from Day 18. It was found that the phases of pups' activity on the day of weaning were similar to the phases of their mother's rhythm (p < 0.001), indicating that maternal entrainment occurs in the C57BL/6J pups. When the mother mouse was cyclically presented to the pups for 12 h of a day, thereby creating presence-absence (PA) cycles of 12:12 h, it was found that the pups' activity rhythm entrained to the imposed cycles. The onset of activity of the pups coincided with the beginning of the mother's 12-h absence period. It is proposed that the social contact between the mother and the pups is taken by the pups as subjective day (rest time) and absence of the mother as subjective night (activity time). This maternal (nonphotic) entrainment, however, does not continue beyond Postnatal Days 23-26, despite ongoing PA cycles. These results indicate that the PA cycles of the mother are a transient zeitgeber, and are effective in entraining the rhythm of pups only for about 4 weeks after birth.     

Visual thalamocortical projections in the flying fox: parallel pathways to striate and extrastriate areas

We studied thalamic projections to the visual cortex in flying foxes, animals that share neural features believed to resemble those present in the brains of early primates. Neurones labeled by injections of fluorescent tracers in striate and extrastriate cortices were charted relative to the architectural boundaries of thalamic nuclei. Three main findings are reported: First, there are parallel lateral geniculate nucleus (LGN) projections to striate and extrastriate cortices. Second, the pulvinar complex is expansive, and contains multiple subdivisions. Third, across the visual thalamus, the location of cells labeled after visual cortex injections changes systematically, with caudal visual areas receiving their strongest projections from the most lateral thalamic nuclei, and rostral areas receiving strong projections from medial nuclei. We identified three architectural layers in the LGN, and three subdivisions of the pulvinar complex. The outer LGN layer contained the largest cells, and had strong projections to the areas V1, V2 and V3. Neurones in the intermediate LGN layer were intermediate in size, and projected to V1 and, less densely, to V2. The layer nearest to the origin of the optic radiation contained the smallest cells, and projected not only to V1, V2 and V3, but also, weakly, to the occipitotemporal area (OT, which is similar to primate middle temporal area) and the occipitoparietal area (OP, a "third tier" area located near the dorsal midline). V1, V2 and V3 received strong projections from the lateral and intermediate subdivisions of the pulvinar complex, while OP and OT received their main thalamic input from the intermediate and medial subdivisions of the pulvinar complex. These results suggest parallels with the carnivore visual system, and indicate that the restriction of the projections of the large- and intermediate-sized LGN layers to V1, observed in present-day primates, evolved from a more generalized mammalian condition.     

A direct projection from the nucleus oculomotorius to the retina in rats

The centrifugal projection to the eye has been studied in rats with anterograde and retrograde tracing techniques. As a retrograde tracer Nuclear Yellow (NY) was used. Following NY injections into the vitreous body of the eye, labeled neurons were exclusively found bilaterally in nucleus oculomotorius. The course and termination site of the retinopetal fibers were studied with the anterograde tracer Phaseolus vulgaris-leucoagglutinin (PHA-L). Iontophoretic injections of PHA-L in nucleus oculomotorius resulted in labeling of retinopetal fibers which reach the eye via the optic tract and optic nerve. Preterminal arborizations were found in the inner nuclear layer of the retina. In addition, labeled fibers have been observed which seem to terminate within the optic tract and optic nerve. It is suggested that the projection from the nucleus oculomotorius to the retina constitutes a link in the multisynaptic efferent pathway from the visual cortex to the eye, by which the visual cortex can influence the functioning of the retina.     

Residual tectal projection from the contralateral central retina of the frog after homolateral optic nerve and main optic tract section

Summary After homolateral (right) optic nerve and main optic tract section a residual visual activity originating from the contralateral (left) central retina was recorded in the right optic tectum. Units were classified in three groups according to their receptive field properties: (1) slow-adapting units analogous to class 3 retinal ganglion cells; (2) fast-adapting post-synaptic units; (3) visual neurons. All of these units have in common a receptive field located near the projection of the left eye optic axis. Evidence that these units belong to the same visual pathway (i.e., the axial optic tract) is discussed.Supported by a grant from the CNRS (AI 3313)     

Retinofugal projections in the rufous horseshoe bat, Rhinolophus rouxi

Summary The retinal projections in the horseshoe bat were studied with anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase. Retinal fibers clearly terminate bilaterally in the lateral geniculate nuclei, superior colliculus, pretectal area, and nucleus of the optic tract. The suprachiasmatic nucleus and the lateral terminal nucleus of the accessory optic tract receive extremely weak, though bilateral retinal input. No projections to medial and dorsal accessory optic nuclei were found. There was a limited retinal projection to the ipsilateral dorsal geniculate nucleus. The focus of the ipsilateral projection corresponded to a less densely labeled region on the contralateral side. In this study an ipsilateral retinal projection to the anterior superior colliculus is documented for the first time in a Microchiropteran bat. In the contralateral superior colliculus retinal fibers terminate in a patch-like pattern at caudal levels.Abbreviations BSC brachium of the SC - CH optic chiasm - CP cerebral peduncle - IGL intergeniculate leaflet - dLGN dorsal lateral geniculate nucleus - vLGN ventral lateral geniculate nucleus: d dorsal, i intermediate, v ventral subdivision - LTN lateral terminal nucleus of accessory optic system - MGN medial geniculate nucleus - NOT nucleus of the optic tract - NSCH suprachiasmatic nucleus - ON optic nerve - OT optic tract - PA pretectal area - PON pretectal olivary nucleus - Rh.r. Rhinolophus rouxi - SC superior colliculus     

Axonal bifurcation of cat retinal ganglion cells as demonstrated by retrograde double labelling with fluorescent dyes

The projections of cat retinal ganglion cells were investigated using fluorescent tracers. After injection of one fluorochrome into the lateral geniculate nucleus (LGN) and the other into the superior colliculus (SC), members of all three ganglion cell classes showed double-labelled somata, indicating axonal bifurcations in the optic tract. No bifurcations were found in the optic chiasm.     

A specific projection of retinal displaced ganglion cells to the nucleus of the basal optic root in the chicken.

The displaced ganglion cells of Dogiel are a class of retinal ganglion cells whose perikarya are located along the inner margin of the inner nuclear layer. Found in all vertebrate classes, they are particularly conspicuous in avians. Recently, Karten, Fite &; Brecha (1977) found that these cells in the pigeon gave rise to a seemingly exclusive projection to the contralateral nucleus of the basal optic root, the major component of the avian accessory optic system. In the present work, the projections of displaced ganglion cells were investigated in hatchling and adult chickens. The cells were found to project to the nucleus of the basal optic root but not to the tectum. Labeled displaced ganglion cells following injections of horseradish peroxidase into the nucleus of the basal optic root were 15 × 20μm in size in both hatchlings and adults. Labeled cells tended to have a higher concentration in the peripheral than in the central retina. Cells were widely but irregularly spaced, with adjacent cells seldom closer than 100 μm. Up to 7700 displaced ganglion cells were labeled in the adult chicken.These results, together with those of Kartenet al. (1977), suggest that in birds, displaced ganglion cells may constitute a unique class of retinal ganglion cells that project exclusively to the nucleus of the basal optic root. In light of the projections of the nucleus of the basal optic root to the oculomotor complex and vestibulocerebellum, the displaced ganglion cells may be an initial link in a visual pathway involved in the control of oculomotor reflexes.