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

The circadian clock in the suprachiasmatic nucleus (SCN) receives direct retinal input via the retinohypothalamic tract (RHT), and the retinal ganglion cells contributing to this projection may be specialized with respect to direct regulation of the circadian clock. However, some ganglion cells forming the RHT bifurcate, sending axon collaterals to the intergeniculate leaflet (IGL) through which light has secondary access to the circadian clock. The present studies provide a more extensive examination of ganglion cell bifurcation and evaluate whether ganglion cells projecting to several subcortical visual nuclei contain melanopsin, a putative ganglion cell photopigment. The results showed that retinal ganglion cells projecting to the SCN send collaterals to the IGL, olivary pretectal nucleus, and superior colliculus, among other places. Melanopsin-immunoreactive (IR) ganglion cells are present in the hamster retina, and some of these cells project to the SCN, IGL, olivary pretectal nucleus, or superior colliculus. Triple-label analysis showed that melanopsin-IR cells bifurcate and project bilaterally to each SCN, but not to the other visual nuclei evaluated. The melanopsin-IR cells have photoreceptive characteristics optimal for circadian rhythm regulation. However, the presence of moderately widespread bifurcation among ganglion cells projecting to the SCN, and projection by melanopsin-IR cells to locations distinct from the SCN and without known rhythm function, suggest that this ganglion cell type is generalized, rather than specialized, with respect to the conveyance of photic information to the brain.

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The intergeniculate leaflet (IGL) has widespread projections to the basal forebrain and visual midbrain, including the suprachiasmatic nucleus (SCN). Here we describe IGL-afferent connections with cells in the ventral midbrain and hindbrain. Cholera toxin B subunit (CTB) injected into the IGL retrogradely labels neurons in a set of brain nuclei most of which are known to influence visuomotor function. These include the retinorecipient medial, lateral and dorsal terminal nuclei, the nucleus of Darkschewitsch, the oculomotor central gray, the cuneiform, and the lateral dorsal, pedunculopontine, and subpeduncular pontine tegmental nuclei. Intraocular CTB labeled a retinal terminal field in the medial terminal nucleus that extends dorsally into the pararubral nucleus, a location also containing cells projecting to the IGL. Distinct clusters of IGL-afferent neurons are also located in the medial vestibular nucleus. Vestibular projections to the IGL were confirmed by using anterograde tracer injection into the medial vestibular nucleus. Other IGL-afferent neurons are evident in Barrington's nucleus, the dorsal raphe, locus coeruleus, and retrorubral nucleus. Injection of a retrograde, trans-synaptic, viral tracer into the SCN demonstrated transport to cells as far caudal as the vestibular system and, when combined with IGL injection of CTB, confirmed that some in the medial vestibular nucleus polysynaptically project to the SCN and monosynaptically to the IGL, as do cells in other brain regions. The results suggest that the IGL may be part of the circuitry governing visuomotor activity and further indicate that circadian rhythmicity might be influenced by head motion or visual stimuli that affect the vestibular system.

The intergeniculate leaflet (IGL) is an integral part of the circadian visual system. It receives direct retinal input and relays photic information to the circadian clock in the suprachiasmatic nucleus (SCN) through a geniculohypothalamic tract (GHT). In both rat and hamster, neuropeptide Y immunoreactive (NPY-IR) IGL cells project through the GHT to the SCN. However, the hamster GHT also contains enkephalin-IR (ENK-IR) fibers, presumably of IGL origin. In the present investigations, the IGL was examined for NPY-, ENK-, or dual-IR cells. Their projections to the SCN, contralateral IGL and pretectum were also studied. The results show that the hamster IGL contains both NPY-and ENK-IR neurons and that about 50% of these are immunoreactive to both peptides. Double-label retrograde analysis indicates that cells of each peptide class project to the SCN. Similarly, IGL neurons, many of which are NPY-and ENK-IR, project to the pretectum, particularly the posterior limitans nucleus. While numerous IGL neurons project contralaterally, very few are NPY-or ENK-IR.The distribution of SCN-and pretectum-projecting cells, in conjunction with the distribution of peptide-IR neurons, allows expansion of the IGL definition to include the region medial to the ventral lateral geniculate nucleus (VLG). The VLG is ventrolateral to the IGL and does not contain either neurons projecting to the SCN nor NPY-or ENK-IR cells, but does have numerous neurons projecting to the pretectum. The results substantiate and expand the previous definition of the hamster IGL, elaborate the species difference in IGL organization, and demonstrate the increased breadth of the circadian visual system.

The intergeniculate leaflet (IGL) of the lateral geniculate complex has widespread, bilateral, and reciprocal connections with nuclei in the subcortical visual shell. Its function is poorly understood with respect to its role in visual processing. The most well-known IGL projection, and the only one with a clear function, is the geniculohypothalamic tract (GHT) that terminates in the suprachiasmatic nucleus (SCN), site of the primary circadian clock. The hamster GHT is derived, in part, from IGL neurons containing neuropeptide Y and enkephalin. IGL neurons containing these peptides also project to the pretectal region. The present studies used a combination of immunohistochemical, lesion, and retrograde tracing techniques to study neuron types in the IGL and their projections to hamster SCN and pretectum. Two additional neuromodulators, gamma-aminobutyric acid (GABA) and neurotensin, are shown to be present in IGL neurons. The GABA- and neurotensin-immunoreactive neurons project to the SCN with terminal field patterns very similar to those for neuropeptide Y and enkephalin. IGL neurons of all four types also send projections to the pretectum, but rarely do individual cells project to both the SCN and the pretectum. Nearly all neurotensin is colocalized with neuropeptide Y in IGL neurons, although about half of the neuropeptide Y cells do not contain neurotensin. Otherwise, the extent to which the four neuromodulators are colocalized varies from 6% to 54%. Nearly every SCN neuron appears to contain GABA. In the IGL, the majority of cells studied are not identifiable by GABA immunoreactivity. Putative functions of the various neuromodulator projections from the IGL to pretectum or SCN are discussed.

The hamster intergeniculate leaflet (IGL), part of the circadian rhythm regulatory system, has very extensive interconnections with subcortical visual nuclei. The present investigation describes IGL connections with the hamster diencephalon and telencephalon and compares them with ventral lateral geniculate nucleus (VLG) connections and retinal projections. Connections of the geniculate nuclei were evaluated using anterograde transport of iontophoretically injected Phaseolus vulgaris leucoagglutinin and by retrograde transport of cholera toxin beta fragment. The cholera fragment was also injected intraocularly to trace retinal efferents. The IGL has ipsilateral and contralateral projections to the anterior and posterior hypothalamic nuclei, the ventral preoptic, lateral and dorsal hypothalamic areas, but not to the core ventromedial nucleus and very sparsely to the paraventricular nucleus. There are also IGL projections to the medial and lateral zona incerta, anteroventral, anterodorsal, reuniens, parataenial, paraventricular, centrolateral, central medial, and laterodorsal thalamic nuclei. IGL projections to the telencephalon are found in the horizontal limb of the diagonal band, olfactory tubercle, nucleus of the lateral olfactory tract, posterior bed nucleus of the stria terminalis, ventral pallidum, and in nuclei of the medial amygdala. The only substantial VLG projections are to bed nucleus of the stria terminalis, IGL, medial zona incerta, central medial and laterodorsal thalamic nuclei. Several of the IGL targets, the bed nucleus of the stria terminalis and zona incerta in particular, send projections back to the IGL and VLG. In addition, cells are present in the caudal cingulate cortex that project to both nuclei. Retinal projections are found in many of the regions receiving IGL innervation, including nuclei of the medial basal telencephalon, the posteromedial bed nucleus of the stria terminalis, and nuclei of the hypothalamus. A retinal projection is also visible in the lateral olfactory tract from which it extends rostrally, then medially along the base of the rhinal fissure. Fibers also extend caudally, in a superficial location, to perirhinal cortex. The results further demonstrate the widespread connections of the IGL and support the idea that the IGL modulates olfactory, photic, and circadian rhythm regulation of regulatory physiology and behavior.

The mammalian medial vestibular nucleus (MVe) receives input from all vestibular endorgans and provides extensive projections to the central nervous system. Recent studies have demonstrated projections from the MVe to the circadian rhythm system. In addition, there are known projections from the MVe to regions considered to be involved in sleep and arousal. In this study, afferent and efferent subcortical connectivity of the medial vestibular nucleus of the golden hamster (Mesocricetus auratus) was evaluated using cholera toxin subunit-B (retrograde), Phaseolus vulgaris leucoagglutinin (anterograde), and pseudorabies virus (transneuronal retrograde) tract-tracing techniques. The results demonstrate MVe connections with regions mediating visuomotor and postural control, as previously observed in other mammals. The data also identify extensive projections from the MVe to regions mediating arousal and sleep-related functions, most of which receive immunohistochemically identified projections from the lateral hypothalamic hypocretin (orexin) neurons. These include the locus coeruleus, dorsal and pedunculopontine tegmental nuclei, dorsal raphe, and lateral preoptic area. The MVe itself receives a projection from hypocretin cells. CTB tracing demonstrated reciprocal connections between the MVe and most brain areas receiving MVe efferents. Virus tracing confirmed and extended the MVe afferent connections identified with CTB and additionally demonstrated transneuronal connectivity with the suprachiasmatic nucleus and the medial habenular nucleus. These anatomical data indicate that the vestibular system has access to a broad array of neural functions not typically associated with visuomotor, balance, or equilibrium, and that the MVe is likely to receive information from many of the same regions to which it projects.