Jacques Servière

Vomeronasal activation by urine in the primateMicrocebus murinus: A 2 DG study

SummaryThe vomeronasal system (VNS) seems to be functional in some primates and involved in the detection of urinary signals. Anterograde tracing (WGA-HRP) and evoked metabolic activity (2-DG method) were used in order to clarify the conditions under which the VNS is activated in the prosimian mouse lemur. After WGA-HRP deposition at one of the oral entries of the nasopalatine duct, reaction product was observed within the accessory bulb (AOB). 2-DG experiments show that urine in the volatile phase stimulates the main but not the accessory bulb (AOB). Liquid urine produced bilateral or unilateral activation of AOB depending on whether the stimulation was exclusively unilateral or not; under the same conditions distilled water could not produce 2-DG labelling. It is concluded that VNS is activated by urine in the liquid but not the volatile phase. The biological implications of these results are discussed.

Direct retinal projections of the "non-image forming" system to the hypothalamus, anterodorsal thalamus and basal telencephalon of mink (Mustela vison) brain.

SummaryThe retinal projections of the “non-image forming” system to the hypothalamus, anterodorsal thalamus and basal telencephalon were visualized in adult mink using the anterograde transport of cholera toxin conjugated to horseradish peroxidase injected intraocularly. A major and nearly symmetrical bilateral input of labeled retinal fibers to the suprachiasmatic nuclei was observed. A dense innervation was also evident in both paraventricular nuclei, and in the anterior, lateral and mediobasal hypothalamus on the side contralateral to the injection. Two projections leaving the optic tract at the level of the lateral hypothalamus or after crossing the geniculate body entered the anterior thalamus and ran in a ventro-dorsal or a caudorostral direction before terminating in the stria terminalis. Fibers were also observed in the horizontal limb of the diagonal band of Broca. These observations are compared to those in other mammalian species and discussed according to their possible implication in photoperiodic signal processing.

Daily changes of cytochrome oxidase activity within the suprachiasmatic nucleus of the Syrian hamster

Cytochrome oxidase (CO) activity was studied over a 24-h period in the Syrian hamster suprachiasmatic nucleus (SCN) (site of the biological clock), anterior hypothalamic area (AHA), and motor cortex. The SCN CO activity was highest at the middle of the day (Zeitgeber time (ZT) 05), decreased at the end of the light period (ZT 10) and continued at a low level during the night (ZT 13, 16, 21.5 and 24). AHA and motor cortex showed a similar profile of CO activity and no changes of CO activity were found in animals maintained under darkness (DD). We propose that photic input plays a role in the SCN neuronal activity that modulates metabolic activity on this area.

Increase of rat medial habenular mast cell numbers by systemic administration of cyclophosphamide.

Cyclophosphamide administration generates systemic toxicity having immune and nervous consequences. After focusing on nervous consequences by studying neuronal activity, we now consider cyclophosphamide impact on diencephalic mast cells as part of the brain immune system. Diencephalon, the ultimate sensory relay before neocortical processing, is the only brain structure containing mast cells. Single cyclophosphamide administration (100 mg/(kg 1 ml ip)) was performed in naturally behaving rats and diencephalic mast cell numbers were analyzed once all drug effects had developed (4 h postinjection). Significant increases were observed only in the medial habenular nucleus--bilaterally and especially in its caudal portion. Mast cell increase is temporally related to behavioral impairment and evoked neuronal activity in a restricted number of visceral/limbic extrathalamic structures. The medial habenular nucleus belongs to the limbic system involved in processing emotional reactions and regulation of the autonomic nervous system. Its involvement during toxic challenge is highly compatible with its presumed function in the maintenance of vital functions.

Both [1-14C]glucose and 2-[1-14C]deoxyglucose produce selective iso-frequency labelling in the inferior colliculus of the cat with short stimulation periods

Both [1-14C]glucose and 2-[1-14C]deoxyglucose (2-DG) revealed selective autoradiographic labelling to tones in the inferior colliculus of the cat with short stimulation periods (5-15 min). With longer periods of stimulation (45 min), the selectivity disappeared with glucose but remained with 2-DG. At all stimulation intervals, 2-DG labelling was always more selective than that obtained with glucose. However, the selectivity seen with glucose was good enough to indicate that isotopes of glucose with short half-lives could still be employed to study human functional activity with the positron emission tomography technique, provided that short stimulation periods were used.

Evidence for serotonin influencing the thalamic infiltration of mast cells in rat

Serotonin (5-HT) is involved in neuroimmunomodulation. We analyzed the effects of sumatriptan, a 5-HT(1B/1D) receptor agonist, and ondansetron, a 5-HT(3) receptor antagonist, on thalamic mast cell (TMC) population, the only immunocytes known to infiltrate the brain in physiological conditions. Only sumatriptan was effective, significantly increasing TMC numbers versus controls, and especially those containing 5-HT. 5-HT(1B) receptors are concentrated in the median eminence on non-serotonergic axonal endings, probably hypothalamic terminal fibers, involved in hypothalamic-pituitary neuroendocrine modulating processes. TMC variations could reflect serotonergic actions on these fibers. TMCs would thus be cellular interfaces mediating immune action in the nervous system in relation with the hormonal status of the organism.

Host resets phase of grafted SCN: influence of implant site, tissue specificity and pineal secretion

The suprachiasmatic nuclei (SCN) have daily fluctuations in energy consumption with glucose utilization high in the day, and low at night. In a previous study, we used [14C]2-deoxyglucose (2-DG) uptake to index the phase of the SCN, and found that in intact hamsters bearing SCN grafts in the third ventricle (3V), the native and grafted SCN, which were initially 12 h out of phase, became synchronized to the phase of the host clock [32]. In the present study, adult males (host animals) and pregnant females (source of donor tissue) were housed in opposite light-dark cycles. Host animals were sacrificed 14 days after implantation with either (1) SCN grafts into the lateral ventricle (LV), or (2) cortical grafts into 3V, or (3) SCN grafts in 3V of pinealectomized hamster. The results indicate that rhythms of 2-DG uptake are not induced in cortical tissue grafts, that the host SCN does not entrain SCN grafts located in the LV, and that entrainment of the grafted SCN (located in 3V) by the host circadian system occurs in the absence of pineal secretions.

Host resets phase of grafted suprachiasmatic nucleus : a 2-DG study of time course of entrainment

The object of the present experiment was to examine whether in an intact animal implanted with a hypothalamic graft, the phase of the host and grafted suprachiasmatic nucleus (SCN) would become synchronized. To this end, we first established the time at which daily fluctuations in local cerebral glucose utilization were maximal in the SCN in our population of adult hamsters. Next, we verified that rhythms of (14C)2-deoxyglucose uptake could be measured on the day after birth in pups that were to provide donor tissue. Host and donor animals were housed in opposite light:dark cycles. We then transplanted fetal SCN tissue into the third ventricle of intact hamsters, placed the grafted animals in constant darkness with access to running wheels and examined the phase of metabolic activity in host and donor SCN. For several days after grafting, there was no circadian fluctuation in the metabolic activity of either the host SCN or of the grafted SCN. During this time, the circadian locomotor rhythms were not disrupted, suggesting that pacemaker activity was not interrupted. By day 14 after transplantation, metabolic activity in the host SCN was elevated during subjective day and host and donor SCN were in synchrony, invariably with the phase of the host animal. We conclude that a signal from the host SCN resets the grafted SCN and not vice versa and that pacemaker cells communicate with each other rather than exerting independent effects on target sites.

Effect of Aging on Circadian Activity in Gray Mouse Lemurs

Microcebus murinus s a very photoperiod-dependent primate with a potentially extended longevity (13 years). Reduction of artificial seasonal cycles allows acceleration of the aging process. Under these conditions, age is defined according to the number of seasonal cycles. We conducted experiments in order to assess the effects of aging upon (1) the main parameters (period: τ duration: α) of the circadian activity–rest rhythm; and (2) the plasticity of the response to light, which is the main entraining factor of the internal clock. We studied the evolution of τ and α through two types of experiments: a transverse one comparing 36 males of various ages (1–13 seasonal cycles) and a longitudinal one following 2 pairs of males from the same litter (one from each pair was maintained under natural cycle while the other was submitted to a shortened cycle) over 54 months. Results from transverse experiments demonstrated no statistical difference in τ and α with age except in 4 senescent (>10 cycles) subjects in which these two parameters were decreased. Longitudinal experiments confirmed this tendency. The plasticity of responses to light, resynchronization after a shift of the day–night cycle, or shift of activity onset after presentation of a light pulse at various circadian times was unaffected by aging. Taken together, the data demonstrate that the parameters of the circadian activity–rest rhythm remain stable over a long span of life and/or that light remains a powerful entraining parameter even in very old individuals.

The effects of viscero-somatic interactions on thalamic mast cell recruitment in rat developing cystitis

Recently, we reported the involvement of brain cyclooxygenase (COX) in centrally administered corticotropin-releasing factor (CRF)-induced activation of the sympatho-adrenomedullary outflow in rats. In this study, we examined the expression of brain COX isozymes in the spinally projecting neurons using rats injected with monosynaptic retrograde tracer into the spinal intermediolateral cell column. Retrogradely labeled cells were detected in the paraventricular hypothalamic nucleus (PVN), locus coeruleus (LC), raphe nuclei and rostral ventrolateral medulla (RVLM). After central administration of CRF, co-expression of COX-1/c-Fos in the PVN-spinal neurons and of COX-2/c-Fos in the LC-spinal neurons were observed, while co-expression of COXs/c-Fos was not observed in the rapheand RVLM-spinal neurons. These data suggest that COX-1 in the PVN and COX-2 in the LC play roles in the CRF-induced activation of the central sympatho-adrenomedullary outflow in rats.