Fos-immunoreactive Cells Research Articles

Induction of uterine activity with oxytocin in late pregnant rats replicates the expression of c-fos in neuroendocrine and brain stem neurons as seen during parturition.

We investigated whether delivery could be induced with pulsatile oxytocin and whether such treatment activated neurons in the supraoptic nucleus (SON) and putative afferent neurons in the nucleus tractus solitarii and ventrolateral medulla, as seen during spontaneous parturition. Rats were implanted with a jugular venous cannula 1 day before the expected term and on the next morning were given a pulse of oxytocin or saline every 10 min for 4 h. Pulses of 10 and 20 mU oxytocin induced delivery in 77% (14 of 18) of rats, whereas none of the control animals (0 of 9) gave birth during the treatment. Lower doses of oxytocin were not effective at this time in inducing delivery. Animals were killed either before (prepartum groups) or during (parturient groups) delivery, and the brains were processed for immunocytochemistry. Oxytocin treatment induced Fos expression in SON and brain stem neurons in both parturient rats and rats in which parturition was not induced. Fos expression in all sites was significantly higher than that in control prepartum rats, but was similar in extent and distribution to that in spontaneous parturient rats. In the brain stem, a substantial proportion of Fos-immunoreactive cells contained tyrosine hydroxylase-like immunoreactivity, and the number of these cells was increased in response to oxytocin treatment. As only very few Fos-immunoreactive nuclei in either the SON or the nucleus tractus solitarii were observed in virgin rats injected with oxytocin, we suggest that intermittent oxytocin injections in late pregnant rats induce strong uterine activity, which can stimulate magnocellular and putative afferent neurons even before the expulsion of pups.

NMDA receptor-mediated expression of Fos protein in the rat striatum following methamphetamine administration: relation to behavioral sensitization

In order to clarify the possible involvement of N-methyl- d-aspartate (NMDA) receptors in mediating striatal Fos protein induction and behavioral sensitization after methamphetamine administration, we examined the effects of non-competitive NMDA receptor antagonist MK-801 on these phenomena in rats. A single administration of 1.0 and 5.0 mg/kg methamphetamine resulted in a dose-dependent increase in Fos-immunoreactive cells in the medial striatum. Prior exposure to 5.0 mg/kg methamphetamine enhanced ipsilateral rotational behavior in response to subsequent methamphetamine administration in unilateral nigral-lesioned rats (sensitization). Pretreatment with 1.0 mg/kg MK-801 completely prevented both the expression of striatal Fos protein and the development of acute behavioral sensitization following a single injection of 5.0 mg/kg methamphetamine. These results suggest that NMDA receptor-mediated mechanisms contribute to the expression of striatal Fos protein associated with behavioral sensitization that follows exposure to methamphetamine.

C-fos expression in the hypothalamo-pituitary system induced by electroacupuncture or noxious stimulation.

In the anaesthetized rat, low frequency electrical stimulation of the Zusanli acupoint (S36) or noxious thermal stimulation caused by immersing the footpad in water at 52 degrees C caused marked expression of c-fos in the anterior lobe of the pituitary gland, as well as in the arcuate and some nearby hypothalamic nuclei. A similar anterior lobe response was caused by immobilization stress in awake rats but in this case Fos-immunoreactive cells extended into the intermediate lobe and were very abundant in the paraventricular nucleus. It is suggested that the anterior pituitary cells that respond to stress are also activated by acupuncture or painful stimulation. However, the mechanisms of pituitary cell activation seem distinct from those occurring in stress, since different hypothalamic nuclei are involved.

Cortical stimulation induces fos expression in intrastriatal striatal grafts

Innervation of intrastriatal grafts of fetal striatal tissue by host corticostriatal projections has been shown in a number of previous studies in rats. In the work reported here, induction of Fos protein in grafted striatal neurons by electrical stimulation of the host frontoparietal cortex has been used as cell-level marker of corticostriatal postsynaptic responses within the striatal grafts. Unilateral cortical stimulation 30 min before sacrifice led to bilateral widespread and intense Fos induction throughout the normal striatum, although the response was somewhat more intense ipsilaterally and in the dorsolateral rostral striatum. In adult rats whose striatum had been lesioned with ibotenic acid 10–12 days prior to implantation of fetal striatal tissue, 3- and 18-month-old striatal grafts showed Fos immunoreactivity in a considerable number of cells after either bilateral, or ipsilateral (∼30–40% of the density of Fos-immunoreactive cells in the normal striatum) or contralateral cortical stimulation. Double-Fos and -DARPP-32 immunohistochemistry revealed that the Fos-immunoreactive nuclei were concentrated in the DARPP-32-positive (i.e. striatum-like) patches, which contained ∼60% of the density of Fos-positive nuclei in the normal striatum after either ipsilateral or bilateral stimulation. However, Fos-immunoreactive nuclei were unevenly distributed within the DARPP-32-positive compartment of the graft, with some clusters of Fos-immunoreactive nuclei at 2−3 × the density observed in the normal striatum and other areas with Fos-immunoreactive nuclei present at lower density or absent. Fos induction was also observed in 4-week-old grafts, indicating that functional corticostriatal synaptic contacts develop rapidly. Striatal grafts implanted either in non-lesioned host striatum or in long-term (18 months) lesioned striatum, similarly showed Fos-positive nuclei after cortical stimulation, indicating that host corticostriatal fibers are equally capable of establishing functional synaptic contacts under these conditions. These results indicate that host corticostriatal fibres not only form an axonal network within the graft but also induce postsynaptic responses which may contribute to the observed graft-induced amelioration of lesion-induced behavioural deficits.

Estradiol and progesterone influence the response of ventromedial hypothalamic neurons to tactile stimuli associated with female reproduction

Stimulation of the vagina and cervix, provided by the male during copulation or manually with a probe, causes many behavioral and endocrine changes associated with female reproduction in rats. Previously, we found that vaginal-cervical stimulation (VCS), by mating or manual probing, increases the expression of Fos-immunoreactivity (Fos-IR) in discrete populations of neurons in the preoptic area, mediobasal hypothalamus and midbrain, suggesting that these neurons respond to VCS. The purpose of the present study was to determine if hormonal priming would increase the number of Fos-IR cells following VCS. Contrary to our hypothesis, in Experiment 1 priming animals with a behaviorally effective dose of 17β-estradiol benzoate followed 48 h later by progesterone caused a trend towards a decrease in the number of VCS-induced Fos-IR cells in the ventromedial hypothalamus. In Experiment 2, which was done to confirm this decrease in VCS-induced Fos-IR neurons by hormones, this effect was found to be statistically significant. Furthermore, this hormone-induced decrease in VCS-responsive cells was localized to the ventromedial nucleus of the hypothalamus, an area rich in estrogen and progestin receptors. No effects of hormone treatment on VCS-induced Fos-IR were observed in any other brain regions analyzed. These findings suggest that steroid hormones may elicit some of their effects on female reproductive behavior and physiology by altering the responsiveness of ventromedial nucleus neurons to vaginal-cervical stimulation.

Neural Substrate of a Cerebellar Movement Disorder Induced by Intracerebroventricular Injection of Propidium Iodide in the Rat: A Fos Immunocytochemical Study

Intracerebroventricular (icv) injection of propidium iodide (PI) in the rat results in a transient movement disorder characterized by nystagmus, ataxia, and shaking. In the present study we used c-Fos as a marker for neuronal activation to investigate the neural substrate underlying this movement disorder. PI was injected into the lateral cerebral ventricle of freely moving rats through a previously implanted cannula. Animals were perfused 3 h after the injection and the brains were processed for c-Fos immunocytochemistry. Paired control animals were injected with saline. After PI injection, a significant Fos expression was seen in the cerebral cortex, thalamic midline nuclei, thalamic intralaminar nuclei, hypothalamus, central gray, pontine nuclei, locus coeruleus, vestibular complex, inferior olive, ventrolateral medulla, nucleus of solitary tract, and deep cerebellar nuclei. Few or no Fos immunoreactive cells were seen in the above structures of the control animals. The present study indicates that a large number of neurons located in many different neural structures are activated following icv injection of PI. Second, consistent with the cerebellar feature of the movement disorder, a major Fos expression was found in the cerebellar circuitry (deep cerebellar nuclei, pontine nuclei, vestibular complex, and inferior olive). It reinforces further the assumption that the movement disorder is due to cerebellar dysfunction caused by PI.

Local administration of EAA antagonists blocks light-induced phase shifts and c-fos expression in hamster SCN.

Syrian hamsters were fitted with guide cannulas stereotaxically aimed at the suprachiasmatic nuclei (SCN) and housed in constant darkness in cages equipped with running wheels. Animals received 300-nl injections of either vehicle, CNQX, or MK-801 into the region of the SCN 5 min before a brief (10 min at 20 lx) light exposure. Local administration of either 1 mM CNQX or 1 mM MK-801 at circadian time (CT) 18 significantly inhibited light-induced phase advances (vehicle = 52 +/- 9 min; CNQX = 12 +/- 7 min; MK-801 = 12 +/- 5 min; P < 0.05 relative to vehicle+light group). The effects of both drugs were reversible and dose related. Injection of 1 mM MK-801 at CT13.5 resulted in a 71% inhibition of light-induced phase delays (vehicle = -51 +/- 6 min; MK-801 = -15 +/- 5 min; P < 0.05), while CNQX failed to significantly inhibit light-induced phase delays (-39 +/- 10 min). Local administration of either 1 mM CNQX or MK-801 into the SCN region reduced the number of Fos-immunoreactive cells relative to vehicle-injected controls by approximately 32 and 44%, respectively (vehicle = 951 +/- 79; CNQX = 643 +/- 135, P < 0.05; MK-801 = 533 +/- 143, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

C-Fos proto-oncogene activity induced by mating in the preoptic area, hypothalamus and amygdala in the female rat: role of afferent input via the pelvic nerve

In order to identify brain areas which receive afferent genitosensory input important for mating-induced prolactin release, we compared numbers of Fos-immunoreactive (Fos-IR) cells in brains of intact estrous females 1 h after differential mating stimulation. Numbers of Fos-IR cells were approximately 3-fold higher in the preoptic area (POA), medial amygdala (mAMYG) and bed nucleus of the stria terminalis (BNST) when females received intromissions (I) from males than when they received mounts-without-intromission (M) or were taken directly from their home cage. In the ventrolateral portion of the ventromedial nucleus (VL-VMN), the paraventricular nucleus (PVN) of the hypothalamus and the midbrain central tegmental field (CTF) numbers of Fos-IR cells were significantly higher than home cage levels in groups of females exposed to males regardless of type of mating stimulation received. Bilateral transection of the pelvic nerve eliminated the increases in Fos-IR in POA and mAMYG which occurred in sham-transected females in these areas after intromissions from males. These data demonstrate that afferent input via the pelvic nerve activates cell groups within the POA, mAMYG and BNST and suggests that these areas may be involved in initiation of mating-induced prolactin surges.

Fos expression in the rat brain following vaginal-cervical stimulation by mating and manual probing.

Vaginal-cervical stimulation (VCS), provided by mating or manual probing, induces many reproductive behavioral and endocrine changes in female rats. These changes include an increase in lordosis duration, heat termination and pseudopregnancy. Electrophysiological and [14C]2-deoxy-D-glucose studies collectively show that neurons in the medial preoptic area, ventromedial hypothalamus and midbrain central gray respond to manual VCS. In the present study we immunocytochemically labeled brain sections for Fos, the protein product of the immediate early gene c-fos, to detect VCS-responsive neurons in hormone-primed animals receiving VCS by mating or manual probing. In Experiment 1, females receiving mounts and intromissions were compared to: 1) vaginally-masked females receiving mounts but no VCS, 2) females exposed to an intact anesthetized male or 3) females not exposed to males or the testing arena. Those animals receiving VCS showed a dramatic increase in the number of Fos-immunoreactive cells in the medial preoptic area, posterodorsal portion of the medial amygdala and bed nucleus of the stria terminalis, as well as the dorsomedial hypothalamus, ventromedial hypothalamus and midbrain central gray. These effects of VCS were confirmed in Experiment 2 in animals receiving manual vaginal-cervical probing. These findings extend previous electrophysiological and [14C]2-deoxy-D-glucose studies by providing evidence that additional brain areas respond to VCS by mating, as well as manual probing.

Immunohistochemical study of the pattern of rapid expression of c‐fos protein in the visual cortex of dark‐reared kittens following initial exposure to light

Brief alterations to the nature of the visual input during critical periods in the early life of cats and monkeys can result in rapid anatomical and physiological changes in the central visual pathways. The immediate early genes (IEGs) represent a possible way in which these changes could be mediated since the protein products of a number of these genes have been shown to be induced rapidly in neurons in response to a variety of transsynaptic stimuli. Immunohistochemical methods were employed to examine the tempo and pattern of expression of Fos, the protein product of the c-fos gene, induced in the visual cortex of kittens dark-reared from birth to 30 days of age by brief periods of binocular visual exposure. In visual cortical area 17, the number of Fos immunoreactive cells increased rapidly from virtually zero in control kittens that received no visual exposure, to reach high levels in animals that received between 1 and 2 hours of visual experience. Immunoreactive cells were absent in the dorsal lateral geniculate nucleus, but were numerous in the ventral lateral geniculate nucleus, and in area 17, were most numerous in the extragranular layers (2, 3 and 6) but sparse in lower layer 4 and layer 5, and virtually absent in layer 1. Substantial constitutive Fos immunoreactivity was observed in area 17 of normal 30-day-old kittens but very few immunopositive cells were evident in adult animals. However, Fos immunoreactivity was observed in the visual cortex of a dark-reared (for 30 days) adult animal following a brief period of visual exposure, a finding that suggests that Fos might serve other roles in the visual cortex in addition to those it might play uniquely during development. It is suggested that Fos, in combination with the protein products of a select number of other IEGs, may mediate a variety of rapid changes in the visual cortex including those that underlie visual system plasticity during early postnatal life.

Mating-induced increases in FOS protein in preoptic area and medial amygdala of cycling female rats

Genitosensory stimulation received during mating initiates neural and endocrine changes necessary for pregnancy. The present study examined sites of induction of the protoncogene, c- Fos, after mating in the cycling female rat to determine neural sites activated by such stimulation that might be involved in pregnancy initiation. Two groups of cycling female rats were exposed to males on the evening of proestrus and remained with the male until receiving either 14 mounts-with-intromission including ejaculations (Intromissions) or a control number of mounts-without-intromission (Mounts-Only). These two mating treatments were previously shown to induce pregnancy/pseudopregnancy in 100% and 0% of the animals, respectively. Seventy-five minutes after mating, females were perfused intracardially with 2% paraformaldehyde/2.5% acrolein, and the brains were processed for FOS immunocytochemistry using standard procedures. FOS-immunoreactive cells (FOS-IR) were counted in standard template quadrilaterals in the preoptic area (POA), medial amygdala (mAMYG), and the paraventricular (PVN), ventromedial (VMN), and dorsomedial (DMN) nuclei of the hypothalamus at 50× magnification using a camera lucida. Significantly higher numbers of FOS-IR cells were seen in Intromissions females above Mounts-Only females in the POA and mAMYG, demonstrating that c- Fos expression in these areas depended upon cervical-vaginal stimulation rather than on cutaneous somatosensory input received in Mounts-Only tests. The cells within the POA and mAMYG that are activated in response to the intromittive stimulus may be directly involved in pathways triggering one or several of the neuroendocrine responses to mating in the female rat.

Fos-like immunoreactivity in the rat hypothalamic-pituitary axis after immobilization stress.

The effect of immobilization stress on the expression of the protooncogene c-fos in the rat pituitary and hypothalamus was investigated immunohistochemically using different polyclonal antibodies raised against the c-fos protein (Fos). After a 4 h immobilization, Fos-like immunoreactivity (Fos-LI) increased substantially in the parvocellular part of the paraventricular nucleus and in the intermediate and anterior lobe of the pituitary. The majority of the Fos-immunoreactive cells in the pituitary contained corticotropin, which was demonstrated by immunohistochemical double-staining. Since the paraventricular nucleus contains a large number of glucocorticoid receptor immunoreactive cells, the effect of a synthetic glucocorticoid, dexamethasone, on the induction of Fos-LI was studied. Dexamethasone treatment before immobilization considerably reduced the stress-induced expression of Fos-LI in the anterior and intermediate lobe of the pituitary but did not alter the induction of Fos-LI in the paraventricular nucleus. The present results demonstrate that immobilization stress induces Fos-LI both in the hypothalamus and in the pituitary, suggesting that Fos may be involved in regulating the synthesis of different mediators of stress response, such as CRF- and POMC-derived peptides. Apparently glucocorticoids do not directly repress c-fos expression, since dexamethasone did not affect the induction of Fos-LI in the paraventricular nucleus. The reduction of stress-induced Fos-LI in the pituitary by dexamethasone is possibly due to the diminished release of CRF factor from the paraventricular neurons.

Different populations of cells in the suprachiasmatic nuclei express c- fos in association with light-induced phase delays and advances of the free-running activity rhythm in hamsters

Circadian rhythmicity is controlled by a light-entrainable pacemaker located in the suprachiasmatic nuclei (SCN) of the mammalian hypothalamus. Brief light exposure during the subjective night causes phase shifts of the free-running activity rhythm and expression of c- fos-related proteins (Fos) among a population of cells in the hamster SCN. Light exposure (30 lux for 15 min) during the early subjective night (CT13) causes phase delays (−60 ± 12 min), while exposure at mid-subective night (CT18) causes phase advances (114 ± 48 min) of t free-running activity rhythm. Light exposure at mid-subjective day (CT6) does not cause phase alterations of the rhythm. Similarity, only light exposure at CT13 or CT18 induces Fos expression in the SCN. The distributi on of Fos-immunoreactive cells in the SCN is more widespread in animals stimulated with light at CT18. In addition, a group of cells located dorsal and anterior to the SCN express Fos only after stimulation at CT18. The data are consistent with the hypothesis that Fos expression represents an event in the signal transduction pathway leading to light-induced alterations in circadian pacemaker function. Furthermore, the data raise the possibility that different populations of cells in the suprachiasmatic hypothalamus may participate in light-induced phase advances and delays of the circadian pacemaker.

Dopaminergic transplants normalize amphetamine- and apomorphine-induced Fos expression in the 6-hydroxydopamine-lesioned striatum

Dopamine receptor-mediated Fos protein expression in the striatum has been used to monitor dopamine receptor activation at the cellular level after dopaminergic denervation and reinnervation by fetal nigrat transplants. The pattern of striatal Fos expression after systemic administration of either the dopamine receptor agonist, apomorphine, or the dopamine-releasing agent, amphetamine, was studied in rats which had received cell suspension grafts of fetal ventrat mesencephalic neurons into the striatum after a complete 6-hydroxydopamine lesion of mesostriatal dopaminergic projection. Grafted animals, and normal and lesioned controls were killed 2 h after administration of either d-amphetamine (5 mg/kg, i.p.) or apomorphine (0.25 mg/kg, s.c.). Fos protein was detected immunohistochemically, and the density of Fos-immunoreactive cell nuclei was measured in 12 selected areas of caudate-putamen, nucleus accumbens and globus pallidus by computerized image analysis. Consistent with previous studies, amphetamine induced high Fos expression in the medial and dorsal parts of the intact caudate-putamen and significantly lower expression in the denervated caudate-putamen. A significant difference between lesioned and intact striata was present also in globus pallidus, but not in nucleus accumbens. In grafted rats, amphetamine-induced Fos activation was restored to normal or supranormal levels in the anterior and centrat caudate-putamen (i.e. close to the graft deposits), whereas in the tail of caudate-putamen Fos expression was significantly lower than normal. The side-to-side difference in globus pallidus seen in lesioned rats was no longer present in the grafted animals. Apomorphine led to high Fos activation throughout the dopamine-depleted caudate-putamen, whereas only very few immunopositive cells were observed in the intact caudate-putamen. Also in globus pallidus and nucleus accumbens, a significantly higher number of Fos-immunoreactive cells was detected on the denervated side. In the grafted rats, apomorphine-induced Fos activation was similar to normal in all striatal areas sampled, as well as in the globus pallidus. The graft-induced effect extended over a considerably larger area than that covered by the graft-derived tyrosine hydroxylase-immunoreactive innervation. These findings indicate that fetal ventrat mesencephalic transplants normalize dopamine receptor mediated function in the 6-hydroxydopamine-lesioned caudate-putamen and nucleus accumbens, as well as in a primary target of the striatal output neurons, the globus pallidus. The results support the idea that dopamine released from the grafted neurons, both under baseline conditions and after amphetamine administration, exerts functional effects over a larger volume of the striatum than that reached by the graft-derived fibers.

C-fos Induction in the Spinal Cord after Peripheral Nerve Lesion.

Immunocytochemical localization of a product of the proto-oncogene c-fos, Fos protein, was used to map the activity of a subset of rat spinal neurons at 3 days, 3 weeks and 3 months following section of the sciatic nerve. In a well-established experimental paradigm, the gene was induced by activation of primary afferent fibres with brief noxious sensory stimulation under anaesthetic. Central sciatic projections were demonstrated with isolectin B4 counterstain and GAP-43 immunocytochemistry. In Rexed's lamina II of the spinal cord, in which there is somatotopic organization of afferent terminals, Fos-positive neurons were largely restricted to the projection area of intact peripheral nerves. Three days after a sciatic nerve lesion, the number of Fos-positive neurons in a cord region innervated by the saphenous nerve was similar to control levels, but was markedly increased by 3 weeks, remaining elevated at 3 months. Three weeks after sciatic nerve section the lectin stain in the area of sciatic representation had almost completely disappeared, and conversely GAP-43 staining had greatly intensified. There was no evidence of invasion by Fos-immunoreactive cells of the area of sciatic representation. After 3 months both the size and the intensity of the lectin gap, and of the corresponding area of increased GAP-43 immunoreactivity, appeared reduced. Thus a peripheral nerve lesion was followed by a delayed increase in excitability of the spinal cord as assessed by c-fos expression, so that greater numbers of second-order neurons were activated by sensory stimulation of an adjacent intact nerve. These changes may be related to the sensory abnormalities which follow nerve damage.

Fos expression in GHB– induced generalized absence epilepsy in the thalamus of the rat

Using the model of gamma-hydroxybutyrate (GHB)-induced generalized absence epilepsy, the present work investigated the distribution of fos oncoprotein expression in the rat thalamus with fos antibody immunohistochemistry. Thirty minutes after absence-like seizures, some fos-immunoreactive cell nuclei were found in bilateral thalamic paraventricular nuclei (PV). After a further 30 min, a massive bilateral induction of fos was observed in the lateral habenular nucleus (LHb), the PV, the rhomboid thalamic nucleus, and the intralaminar nuclei of the thalamus. These results suggest that the LHb and the midline and intralaminar thalamic nuclei may very likely be involved in the pathophysiology of absence seizures.

Circadian rhythm in c- fos protein expression in the rat adrenal cortex

The circadian variation in the expression of c- fos protein(s) in the adrenal cortex of adult rats was investigated immunocytochemically. The animals were maintained in standard laboratory facilities with a 12 : 12 h light : dark schedule (07.00–19.00 h) until sacrificed. The number of c- fos immunoreactive (c- fos IR) cells was statistically constant in the zona fasciculata and zona reticulata at 20.00 h and 24.00 h, and 04.00 h, but was decreased to 52% at 08.00 h and to 18% at 12.00 h, respectively, when compared to the 24.00 h value. At 16.00 h, the number of c- fos IR cells was increased again to 63% of the 24.00 h value. In the zona granulosa c- fos IR was observed only at 20.00 h and 24.00 h. Administration of dexamethasone, a potent inhibitor of ACTH release, significantly reduced the number of c- fos IR cells. As the circadian rhythm of c- fos expression in the adrenal cortex correlates to that reported for ACTH secretion from the pituitary, the results suggest that c- fos gene is involved in mediating physiological ACTH-induced responses in the adrenal cortical cells.

Light increases Fos-related protein immunoreactivity in the rat suprachiasmatic nuclei

Fifteen minutes of bright, white light exposure at midsubjective night resulted in a marked increase in both the number and stain density of c-fos protein (Fos)-immunoreactive neurons in the suprachiasmatic nuclei (SCN). In all cells, peroxidase reaction product was confined to the nucleus. Most Fos-immunoreactive cells were concentrated in the ventrolateral third of the SCN, although a few immunoreactive cells were also observed diffusely distributed along the dorsal border of the nucleus and into the surrounding hypothalamus. Along the rostro-caudal extent of the SCN, the greatest density of Fos-immunoreactive cells was found at a level approximately 300–400 μm caudal of the rostral pole of the nucleus. The population of Fos-immunoreactive cells in the SCN lies within the terminal fields of both the retinohypothalamic and geniculohypothalamic tracts. In addition, a few Fos-immunoreactive cells were observed in the ventral lateral geniculate nucleus. The results suggest that retinal illumination induces transsynaptic c-fos expression in a select population of SCN neurons.