Functional anatomy of the thalamus in the blind mole rat Spalax ehrenbergi: An architectonic and electrophysiologically controlled tracing study

The occipital cortex of the naturally blind mole rat, Spalax ehrenbergi, is occupied by an area of somatosensory representation. To date, no visual cortex has been identified electrophysiologically. In order to determine whether there are corresponding modifications in the thalamus, thalamocortical connections were studied with neuroanatomical tracing methods. Three different fluorescent tracers were injected under electrophysiological control into distinct cortical areas. Injections into the somatosensory head/face and hindlimb/trunk areas of representation revealed a posteromedial ventral nucleus and a posterolateral ventral nucleus, respectively. Additional somatotopic labeling was found in an area dorsomedial to the two ventral nuclei. This structure may be equivalent to the posterior nuclear complex in the laboratory rat. Injections into the auditory cortex of the mole rat resulted in labeling of the medial geniculate body. In contrast to the situation in the laboratory rat, in which a prominent dorsolateral geniculate body and a ventrolateral geniculate body assume dorsolateral positions, the somatosensory thalamus of the mole rat almost reaches the dorsolateral surface. This finding is corroborated by the results of the architectonic study, which failed to reveal a differentiated lateral geniculate body. Our observations suggest that the thalamocortical visual system in the mole rat is minute, whereas the somatosensory system is expanded. This situation fits the mode of life of this subterranean animal, for which touch is more important than vision. © 1994 Wiley-Liss, Inc.     

Auditory activation of "visual" cortical areas in the blind mole rat (Spalax ehrenbergi)

The mole rat (Spalax ehrenbergi) is a subterranean rodent whose adaptations to its fossorial life include an extremely reduced peripheral visual system and an auditory system suited for the perception of vibratory stimuli. We have previously shown that in this blind rodent the dorsal lateral geniculate nucleus, the primary visual thalamic nucleus of sighted mammals, is activated by auditory stimuli. In this report we focus on the manifestation of this cross-modal compensation at the cortical level. Cyto- and myeloarchitectural analyses of the occipital area showed that despite the almost total blindness of the mole rat this area has retained the organization of a typical mammalian primary visual cortex. Application of the metabolic marker 2-deoxyglucose and electrophysiological recording of evoked field potentials and single-unit activity disclosed that a considerable part of this area is activated by auditory stimuli. Previous neuronal tracing studies had revealed the origin of the bulk of this auditory input to be the dorsal lateral geniculate nucleus which itself receives auditory input from the inferior colliculus.     

Adaptive loss of ultraviolet-sensitive/violet-sensitive (UVS/VS) cone opsin in the blind mole rat (Spalax ehrenbergi)

In previous studies, fully functional rod and long-wavelength-sensitive (LWS) cone photopigments have been isolated from the eye of the subterranean blind mole rat (Spalax ehrenbergi superspecies). Spalax possesses subcutaneous atrophied eyes and lacks any ability to respond to visual images. By contrast this animal retains the ability to entrain circadian rhythms of locomotor behaviour to environmental light cues. As this is the only known function of the eye, the rod and LWS photopigments are thought to mediate this response. Most mammals are dichromats possessing, in addition to a single rod photopigment, two classes of cone photopigment, LWS and ultraviolet-sensitive/violet-sensitive (UVS/VS) with differing spectral sensitivities which mediate colour vision. In this paper we explore whether Spalax is a dichromat and has the potential to use colour discrimination for photoentrainment. Using immunocytochemistry and molecular approaches we demonstrate that Spalax is a LWS monochromat. Spalax lacks a functional UVS/VS cone photopigment due to the accumulation of several deleterious mutational changes that have rendered the gene nonfunctional. Using phylogenetic analysis we show that the loss of this class of photoreceptor is likely to have arisen from the visual ecology of this species, and is not an artefact of having an ancestor which lacked a functional UVS/VS cone photopigment. We conclude that colour discrimination is not a prerequisite for photoentrainment in this species.     

Auditory pathway and auditory activation of primary visual targets in the blind mole rat (Spalax ehrenbergi): I. 2-deoxyglucose study of subcortical centers

The blind mole rat Spalax ehrenbergi is a subterranean rodent that shows striking behavioral, structural, and physiological adaptations to fossorial life including highly degenerated eyes and optic nerves and a behavioral audiogram that indicates high specialization for low-frequency hearing. A 2-deoxyglucose functional mapping of acoustically activated structures, in conjunction with Nissl/Klüver-Barrera-stained material, revealed a typical mammalian auditory pathway with some indications for specialized low-frequency hearing such as a poorly differentiated lateral nucleus and a well-developed medial nucleus in the superior olive complex. The most striking finding was a marked 2-deoxyglucose labeling of the dorsal lateral geniculate body and of cortical regions that correspond to visual areas in sighted rodents. The results render the blind mole rat a good model system for studying natural neural plasticity and intermodal compensation. In this report, we confine ourselves to the subcortical levels. The cortical level will be dealt comprehensively in a following paper.     

The visual system of a Palaeognathous bird: Visual field,retinal topography and retino‐central connections in the Chilean Tinamou (Nothoprocta perdicaria)

Most systematic studies of the avian visual system have focused on Neognathous species, leaving virtually unexplored the Palaeognathae, comprised of the flightless ratites and the South American tinamous. We investigated the visual field, the retinal topography, and the pattern of retinal and centrifugal projections in the Chilean tinamou, a small Palaeognath of the family Tinamidae. The tinamou has a panoramic visual field with a small frontal binocular overlap of 20°. The retina possesses three distinct topographic specializations: a horizontal visual streak, a dorsotemporal area, and an area centralis with a shallow fovea. The maximum ganglion cell density is 61,900/ mm², comparable to Falconiformes. This would provide a maximal visual acuity of 14.0 cycles/degree, in spite of relatively small eyes. The central retinal projections generally conform to the characteristic arrangement observed in Neognathae, with well‐differentiated contralateral targets and very few ipsilateral fibers. The centrifugal visual system is composed of a considerable number of multipolar centrifugal neurons, resembling the “ectopic” neurons described in Neognathae. They form a diffuse nuclear structure, which may correspond to the ancestral condition shared with other sauropsids. A notable feature is the presence of terminals in deep tectal layers 11–13. These fibers may represent either a novel retinotectal pathway or collateral branches from centrifugal neurons projecting to the retina. Both types of connections have been described in chicken embryos. Our results widen the basis for comparative studies of the vertebrate visual system, stressing the conserved character of the visual projections' pattern within the avian clade. J. Comp. Neurol. 523:226–250, 2015. © 2014 Wiley Periodicals, Inc.     

Responses of cells in the rat supraoptic nucleus in vivo to stimulation of afferent pathways are different at different times of the light/dark cycle

To determine whether the daily rhythms of spike activity in the supraoptic nucleus (SON) were accompanied by changes in the behaviour of its inputs, we used conventional extracellular single cell recordings from cells in the SON of anaesthetized rats while stimulating the contralateral optic nerve and the ipsilateral suprachiasmatic nucleus (SCN). Neurones in the SON region were identified by antidromic activation and classified as oxytocin or vasopressin cells, on the basis of their spontaneous firing patterns. Approximately 27% of both oxytocin (29/108) and vasopressin (39/147) neurones were excited by stimulation of the optic nerve, and the majority of responses had a long latency (>20 ms). Very few oxytocin (3/108) and vasopressin cells (2/147) were inhibited by stimulation of the optic nerve. The pattern of the responses (excitatory, inhibitory or nonresponsive) of oxytocin and vasopressin cells to stimulation of the optic nerve was significantly related to the time of day (chi-square test; P = 0.012, oxytocin cells; P = 0.006, vasopressin cells). The proportion of oxytocin cells excited by stimulation of the optic nerve was highest at ZT 4-8 and lowest at ZT 20-24. For vasopressin cells, it was highest at ZT 12-16 and lowest at ZT 20-24. The proportion of excitatory, inhibitory and complex responses seen in oxytocin and vasopressin cells following stimulation of the SCN also changed and was significantly different at different times of day (oxytocin cells: highest proportion of excitatory responses at ZT 12-16, P = 0.029; chi-square test; vasopressin cells: highest proportion of excitatory responses at ZT 0-4, P = 0.005; chi-square test). Thus, inputs to oxytocin and vasopressin neurones from the optic nerve and some outputs from the SCN changed during the light/dark cycle. Such changes may contribute to the generation of 24-h rhythms in activity of oxytocin and vasopressin neurones and release of the peptides.     

Neuroglobin expression in the rat suprachiasmatic nucleus: Colocalization,innervation, and response to light

Neuroglobin (Ngb) is a myoglobin‐like (Mb) heme‐globin, belonging the globin family located only in neuronal tissue of the central nervous system. Ngb has been shown to be upregulated in and to protect neurons from hypoxic and ischemic injury, but the function of Ngb—in particular how Ngb may protect neurons—remains largely elusive. We have previously described the localization of Ngb in the rat brain and found it to be expressed in areas primarily involved in sleep/wake, circadian, and food regulation. The present study was undertaken, using immunohistochemistry, to characterize the localization, colocalization, innervation, and response to light of Ngb‐immunoreactive (IR) cells in the rat suprachiasmatic nucleus (SCN). Our results demonstrate that the majority of Ngb‐expressing neurons in the SCN belong to a cell group not previously characterized by neurotransmitter content; only a small portion was found to co‐store GRP in the ventral SCN. Furthermore, some Ngb‐containing neurons were responsive to light stimulation at late night evaluated by the induction of cFOS and only a few cells were found to express the core clock gene PER1 during the 24‐hour light/dark cycle. The Ngb‐containing cells received input from neuropeptide Y (NPY)‐containing nerve fibers of the geniticulo‐hypothalamic tract (GHT), whereas no direct input from the eye or the midbrain raphe system was demonstrated. The results indicate that the Ngb could be involved in both photic and nonphotic entrainment via input from the GHT. J. Comp. Neurol. 518:1556–1569, 2010. © 2009 Wiley‐Liss, Inc.     

The use of kainic acid for tracing neuroanatomical connections in the septohabenvilointerpeduncular system of the rat

Intracerebral injections of the neuron-destroying agent, kainic acid, and electron microscopic examination of the injected and the target areas, have been used in order to confirm some controversial anatomical connections in the Septohabenulointerpeduncular system. Kainic acid injections in the lateral habenula (LHb) caused the selective degeneration of several LHb neurons, sparing the neurons of the medial habenula (MHb). Degenerating terminals were found in well-known target areas of the LHb (dorsal and median raphe nuclei) and, in addition, in the interpeduncular nucleus (IPN), thus confirming the existence of a small LHb-IPN projection. Kainic acid injections in the nucleus of the diagonal band of Broca (NDBB) resulted in severe ncuronal degeneration in the nucleus itself and in terminal degeneration in the LHb and MHb as well as, to a lesser extent, in the IPN. No evidence of distant neuronal damage was apparent by light (conventional and cupric-silver stain) and electron microscopic examination, in nuclei receiving afferent inputs from the injected areas and projecting in turn to the target areas. Furthermore, terminal degeneration was not observed in the Hb and IPN after injections of kainic acid in areas not projecting toward these nuclei (hippocampus and striatum). In the present study, therefore, problems of interpretation due to the possible occurrence of distant neuronal damage could be overcome by control tests. On the basis of the selectivity and sensitivity of its action, kainic acid seems particularly useful in the study of small projections and in attempts to discriminate between differential connections of adjacent neuronal populations.     

Topographical and ultrastructural investigation of the habenulo-interpeduncular pathway in the rat: a wheat germ agglutinin-horseradish peroxidase anterograde study

The topographical and ultrastructural organization of the habenular projection to the interpeduncular nucleus (IPN) of the rat was examined employing the anterogradely transported tracer wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and the chromogen tetramethylbenzidine (TMB). Unilateral placements of WGA-HRP in the habenular complex resulted in heavy terminal labelling in the rostral, central, and intermediate subnuclei bilaterally, and in the lateral subnuclei ipsilaterally. The apical subnucleus possessed only a sparse amount of label. Placements confined to the medial habenula (mH) produced similar results to those observed when the entire habenula was filled, suggesting that the afferent contribution made by the lateral habenula (lH) to the IPN is small. Unilateral placements of WGA-HRP in the dorsal portion of the mH resulted in heavy, predominantly ipsilateral labelling in the lateral subnucleus and the dorsal cap of the rostral subnucleus. In the lateral subnucleus labelled habenular terminals consistently contacted single dendritic processes shared by one or more other boutons, possibly of nonhabenular origin. Labelled habenular terminals in the rostral subnucleus normally contacted one or two dendrites. Labelled terminals in both subnuclei possessed clear, spherical vesicles and a variable number of dense-core vesicles. Unilateral placements of WGA-HRP in the ventral portion of the mH resulted in heavy labelling in the rostral half of the rostral subnucleus with a slight ipsilateral predominance, and in the central and intermediate subnuclei bilaterally. Terminal labelling was observed in crest and S synapses in the intermediate and central subnuclei respectively. Crest synapses, which consist of two parallel habenular terminals contacting an attenuated dendritic process, normally possessed label in only one of the two boutons. In the central subnucleus labelled horizontal axons formed several en passant S synapses with dendritic processes of small and medium diameter. These synaptic specializations of habenular axons contained numerous clear, spherical vesicles. This study demonstrates that a major topographically organized projection to the IPN originates from two distinct subpopulations of habenular neurons which comprise a dorsal sector and a ventral sector of the mH. Ultrastructural examination demonstrated that axons originating from neurons in the ventral and dorsal mH form characteristic contacts in the various IPN subnuclei.     

In vivo metabolic activity of a putative circadian oscillator,the rat suprachiasmatic nucleus

The suprachiasmatic nucleus (SCN) has been proposed as a site for an endogenous circadian oscillator in mammals, since lesions of the nucleus abolish a wide spectrum of overt circadian rhythms. To demonstrate that a directly measurable property of the SCN itself in intact (unlesioned) animals is affected by environmental light and exhibits circadian rhythmicity, we used the autoradiographic 2-deoxy-D-[¹⁴C]glucose method to determine glucose utilization of rat SCN under a variety of lighting conditions. Our experiments indicate an important role for the SCN in circadian rhythm organization, and we believe the deoxyglucose method will prove useful as a tool for better understanding the functions and mechanisms of circadian clocks.     

Axonal branching of the olivocerebellar projection in the rat: a double-labeling study

Collateralization of olivocerebellar (climbing) fibers was studied in the rat by means of the fluorochrome double-labeling technique. Most of the olivocerebellar projection is crossed except for a minimal ipsilateral component which arises from the most rostal part of the inferior olivary nucleus (ION). ION neurons in the caudolateral part of the medial accessory olive (MAO) and the dorsal accessory olive (DAO) give off axons that branch to supply both hindlimb areas of the contralateral cerebellar cortex, i.e., the rostral anterior lobe and the caudal paramedian lobule. In addition, neurons in the middle one-third of the contralateral MAO and DAO send axons that divide to terminate in both the caudal part of the anterior lobe and the rostral part of the paramedian lobule (forelimb receiving areas). Neurons within the caudal part of the MAO, the lateral part of the DAO, the ventral lamella of the principal olive (PO), and the dorsomedial cell column (DMCC) send axonal branches that terminate within at least two different areas of the same sagittal zones throughout the contralateral cerebellar cortex. Thus, the ION contains specialized cells that provide a divergence of integrated information from the ION to at least two cerebellar regions.     

Effect of constant light, pinealectomy and guanosine triphosphate gamma-s on the density of melatonin receptors in the rat suprachiasmatic nucleus: a possible implication of melatonin action

We report here the effects of pinealectomy and exposition to constant light on the density of melatonin receptors in the suprachiasmatic nuclei of the rat using quantitative autoradiography. The B(max) values were significantly increased when the animals were maintained in constant light for 3 days (8.22 ± 0.95 fmol/mg protein versus 4.55±0.14 fmol/mg protein in control group, 12 h light/12 h dark cycle (12L/12D), n = 6). A similar increase was also observed in rats pinealectomized 3 days before sacrifice and then maintained either under 12L/12D (B(max) 7.56±0.80 fmol/mg protein) or in constant light (B(max) 7.85±1.02 fmol/mg protein), while K(d) values failed to show any variations after constant light and/or pinealectomy. The effect of GTPγS on the density of rnelatonin binding sites was also investigated in control animals and after 3 days of constant light. In 12L/12D animals, the B(max) shifted from 5.94 ± 0.14 fmol/mg protein in the absence of GTPγS to 3.97±0.22 fmol/ mg protein in the presence of 50μiM GTPγS. In animals maintained for 3 days in constant light, a similar decrease in the B(max) value was observed (8.95 ± 0.25 fmol/mg protein in absence and 5.95 ± 0.22 fmol/mg protein in presence of 50 μ GTPγS). In both cases, K(d) values were not affected by GTPγS. Pinealectomy and constant light exposition are known to induce a suppression of the nocturnal peak of plasma rnelatonin and to keep plasma rnelatonin concentrations at a very low level. These results could suggest a regulatory effect of rnelatonin on the density of its own receptors which are shown here to be also coupled with a G-protein.     

Macaque accessory optic system: I. Definition of the medial terminal nucleus

The organization of the accessory optic system (AOS) has been studied in the macaque monkey following intravitreal injections of tritiated amino acids in one eye. Retinal projections to the dorsal (DTN) and the lateral (LTN) terminal nuclei are identical to those previously described in other primate species. We observed an additional group of retinorecipient cells of the AOS, located between the cerebral peduncle and the substantia nigra, which we define as the interstitial nucleus of the superior fasiculus, medial fibers. In this report, we focus our attention on the medial terminal nucleus (MTN). Although a ventral division of this nucleus (MTNv) was not observed in the macaque, the retina projects to a group of cells in the midbrain reticular formation (MRF), which we argue to be homologous to the dorsal division of the MTN (MTNd). To provide evidence in support of this homology, the retinal projection to the MTNv and MTNd was also examined in 21 additional species from 11 orders of mammals including carnivores, marsupials, lagomorphs, rodents, bats, insectivores, tree shrews, hyraxes, pholidotes, edentates, and five additional species of primates. Whereas the retina projects to both ventral and dorsal divisions in all species studied, in haplorhine primates only the projection to the MTNd is conserved. The relative topological position of the MTNd in the MRF, dorsomedial to the substantia nigra and ventrolateral to the red nucleus, remains constant throughout the mammals. The trajectory of fiber paths innervating the MTNd is also similar in all species. In addition, the MTNd has comparable afferent and efferent connections with retina, pretectum, and vestibular nuclei in all species thus far studied. These results support the unequivocal conclusion that the MTNd is an unvarying feature of the mammalian AOS.     

Connections of the hypothalamic paraventricular necleus with the neurohypophysis, median eminence, amygdala, lateral septum and midbrain periaqueductal gray: An electrophysiological study in the rat

Extracellular recordings were obtained from 555 paraventricular (PVN) nucleus neurons in pentobarbital-anesthetized male rats. Cells were examined for their spontaneous activity patterns and response to single 1-Hz electrical stimulation of the neurohypophysis, median eminence, amygdala, lateral septum (LS) and midbrain periaqueductal gray (PAG).Neurohypophyseal stimulation evokedantidromic activation from 109 neurons. Among spontaneouly active neurohypophyseal neurons, evidence of a recurrent inhibitory pathway usually required pituitary stimulus intensities twice threshold for antidromic activation. Orthodromic excitatory or inhibitory responses followed amygdala and LS stimulation, but not PAG stimulation. The amygdala influence was predominantly inhibitory to ‘phasic’ (putative vasopressin-secreting) PVN neurohypophyseal neurons. Neurohypophyseal stimulation evokedorthodromic responses from 124 PVN cells; some of these neurons were also responsive to stimulation in other sites.Median eminence stimulation evoked antidromic responses from 37 PVN neurons; some of these cells also displayed phasic activity but not evidence for recurrent inhibition. Twelve cells in this group were also activated antidromically from both the median eminence and the neurohypophysis; collision tests suggest that the median eminence innervation may be an axon collateral of a neurohypophyseal pathway. Amygdala stimulation was inhibitory to some cells in this category.Amygdala, LS and PAG stimulation evoked antidromic activation from a small number of PVN cells, but none of these cells appeared to innervate more than one area, including the neurohypophysis, and none displayed phasic activity. Orthodromic responses were recorded among other PVN neurons after stimulation in these sites; however, PAG stimulation was the least effective stimulation area.These observations provide additional electrophysiological data that confirm efferent PVN connections to all areas tested, afferent connections from amygdala and LS but not PAG, and the possibility for coordinated activity among PVN neurons through local recurrent or common afferent connections.     

Interconnections among nuclei of the subcortical visual shell: The intergeniculate leaflet is a major constituent of the hamster subcortical visual system

The intergeniculate leaflet (IGL), a major constituent of the circadian visual system, is one of 12 retinorecipient nuclei forming a “subcortical visual shell” overlying the diencephalic–mesencephalic border. The present investigation evaluated IGL connections with nuclei of the subcortical visual shell and determined the extent of interconnectivity between these nuclei. Male hamsters received stereotaxic, iontophoretic injections of the retrograde tracer, cholera toxin β fragment, or the anterograde tracer, Phaseolus vulgaris-leucoagglutin, into nuclei of the pretectum (medial, commissural, posterior, olivary, anterior, nucleus of the optic tract, posterior limitans), into the superior colliculus, or into the visual thalamic nuclei (lateral posterior, dorsal lateral geniculate, intergeniculate leaflet, ventral lateral geniculate). Retrogradely labeled cell bodies identified nuclei with afferents projecting to the site of injection, whereas the presence of anterogradely labeled fibers with terminals revealed brain nuclei targeted by neurons at the site of injection. The IGL projects bilaterally to all nuclei of the visual shell except the lateral posterior and dorsal lateral geniculate nuclei. The IGL also has afferents from the same set of nuclei, except the nucleus of the optic tract. The extensive bilateral efferent projections distinguish IGL from the ventral lateral geniculate nucleus. The superior colliculus, commissural pretectal, olivary pretectal, and posterior pretectal nuclei also project bilaterally to the majority of subcortical visual nuclei. The IGL has a well-established role in circadian rhythm regulation, but there is as yet no known function for it in the larger context of the subcortical visual system, much of which is involved in oculomotor control. J. Comp. Neurol. 396:288–309, 1998. © 1998 Wiley-Liss, Inc.     

Luminance coding in a circadian pacemaker: the suprachiasmatic nucleus of the rat and the hamster

The hypothalamic suprachiasmatic nuclei (SCN) of mammals function as a pacemaker driving circadian rhythms. This pacemaker is entrained to the daily light-dark cycle in the environment via the retina and central retinal projections to the anterior hypothalamus. We carried out a comparative study of the visual properties of rat and hamster SCN neurons. Extracellular single cell activity was recorded in the SCN of urethane-anaesthetized animals. In both species, visual SCN neurons responded to retinal illumination with a sustained increase or a sustained decrease in electrical discharge. The majority (75%) of these cells were activated by light. In both the rat and the hamster SCN, visually responsive cells altered their discharge rate as a monotonic function of luminance. The intensity-response curve could be described by a Michaelis function with a small working range between threshold and saturation (2-3 log units) and a relatively high threshold. Intensity-response curves in both species were occasionally different for increasing as opposed to decreasing luminance. Thus, hysteresis effects of illumination may occur in the SCN. The spontaneous firing rates as well as the responsiveness of visual SCN cells were subject to marked variations between and within cells. The overall photic responsiveness of SCN neurons, however, indicated that they are specialized for luminance coding in the range of light intensities naturally occurring at dawn and dusk. This property makes these cells suitable to mediate photic entrainment of circadian rhythms as well as the measurement of photoperiod.     

Organization of the circadian system in the subterranean mole rat,Cryptomys hottentotus (Bathyergidae)

The mole rat, Cryptomys hottentotus (Bathyergidae) is a gregarious subterranean rodent, which shows no entrainment to ambient light-dark cycles. The locomotor activity of individuals or of a whole colony, which shows no circadian rhythmicity. Since the lack of both synchronization to light-dark cycle and an endogenous rhythm of locomotor activity could be related to the organization of the circadian system, we have investigated the neuropeptidergic features of the SCN and IGL, and have used pseudorabies viral tracing methods to identify the visual and circadian pathways in this species. The precise topographic distribution of certain neuropeptide populations in the SCN differs from typical rodent pattern of organization and may be correlated with the apparent absence of light entrainment of activity and lack of endogenous rhythmicity. The IGL is highly reduced in size. This structure can nevertheless be identified by the presence of NPY and CALB positive neurons, as well as by a dense network of SP fibers. Viral tracing using intraocular injection of the PRV-Becker and PRV-Bartha strains, leads to differential infection of neurons in circadian and visual structures. With the Bartha strain, infected neurons are principally observed in the SCN, whereas the Becker strain leads primarily to infection of the dLGN and shows an anatomical regression of visual structures. Transsynaptic retrograde infection of the retina contralateral to the injected eye reveals a morphologically homogeneous population, which resemble to retinohypothalamic ganglion cells described in other mammals.     

The diencephalon of the pacific herring,Clupea harengus: Retinofugal projections to the diencephalon and optic tectum

The pattern of retinofugal projections to nuclei in the diencephalon and to the optic tectum was analyzed with horseradish peroxidase and autoradiographic methods in Clupea harengus, a clupeomorph teleost, for comparison with osteoglossomorph, elopomorph, and euteleost teleosts and with non-teleost actinopterygians. Most retinal fibers decussate in the optic chiasm and project to nuclei in the preoptic area, ventral and dorsal thalamus, posterior tuberculum, synencephalon, and pretectum, as well as to the accessory optic nuclei and optic tectum. Some ipsilateral projections do not decussate in the optic chiasm, while others decussate and recross via the supraoptic (minor) and posterior commissures. The pattern of projections is similar to that seen in other actinopterygian fishes with several exceptions. The terminal field usually present lateral to nucleus anterior in the dorsal thalamus is extremely reduced despite the relatively large size of the nucleus. A dense terminal field lies within the cell plate of nucleus corticalis in the pretectum rather than dorsal to it. The tectal hemisphere is composed of two distinct lobules, and the dorsal optic tract projects to the more rostromedial lobule while the ventral optic tract projects to the more caudolateral lobule. The lack of a significant projection to nucleus anterior and the lobular morphology of the optic tectum appear to be apomorphic for Clupea. Other features of the pattern of retinal projections are also analyzed in actinopterygian fishes including Clupea, and several hypotheses are advanced as to which traits are plesiomorphic for actinopterygians and/or for teleosts. © 1993 Wiley-Liss, Inc.     

Melatonin: a clock-output,a clock-input

In mammals, the circadian system is comprised of three major components: the lateral eyes, the hypothalamic suprachiasmatic nucleus (SCN) and the pineal gland. The SCN harbours the endogenous oscillator that is entrained every day to the ambient lighting conditions via retinal input. Among the many circadian rhythms in the body that are driven by SCN output, the synthesis of melatonin in the pineal gland functions as a hormonal message encoding for the duration of darkness. Dissemination of this circadian information relies on the activation of melatonin receptors, which are most prominently expressed in the SCN, and the hypophyseal pars tuberalis (PT), but also in many other tissues. A deficiency in melatonin, or a lack in melatonin receptors should therefore have effects on circadian biology. However, our investigations of mice that are melatonin-proficient with mice that do not make melatonin, or alternatively cannot interpret the melatonin message, revealed that melatonin has only minor effects on signal transduction processes within the SCN and sets, at most, the gain for clock error signals mediated via the retino-hypothalamic tract. Melatonin deficiency has no effect on the rhythm generation, or on the maintenance of the oscillation. By contrast, melatonin is essential for rhythmic signalling in the PT. Here, melatonin acts in concert with adenosine to elicit rhythms in clock gene expression. By sensitizing adenylyl cyclase, melatonin opens a temporally-restricted gate and thus lowers the threshold for adenosine to induce cAMP-sensitive genes. This interaction, which determines a temporally precise regulation of gene expression, and by endocrine-endocrine interactions possibly also pituitary output, may reflect a general mechanism by which the master clock in the brain synchronizes clock cells in peripheral tissues that require unique phasing of output signals.