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J Serviere

Publications and source records attributed to J Serviere.

7 recordsLinked to original sources

[Understanding the action of the circadian clock: from phenomenologic ideas to molecular activity].

The focus of the present review is to present recent studies of the mammalian circadian clock located in the suprachiasmatic nuclei (SCN) of the hypothalamus. The main questions in circadian neuroscience are: how many oscillators are implicated, how are their daily oscillations generated and synchronized to the external environment and how does the central clock send timed signals to the whole organism. The review is introduced by a presentation of circadian system properties and by a description of the responses to manipulations of the main entraining factor, i.e. the light-dark cycle. The anatomy of the SCN and its major afferents from the retina (glutamate, Substance P), raphe (serotonin) and intergeniculate leaflet (neuropeptide Y) of the thalamus are presented with a special emphasis on the interaction of these inputs with the circadian timekeeping mechanism. The arguments related to the issue of whether the retina contain an endogenous oscillator are exposed. What is known of the endogenous mechanism(s) of this small structure containing 10,000 or so "self-oscillating neurons" is reviewed through: i) the anatomical distribution and functional significance of clock-peptides (VIP, PHI, GRP, VP or SS), ii) the putative involvement of the SCN astrocytic population in coordinating neuronal activities, iii) the various aspects of cellular activity (electrical activity, energy metabolism, protein or peptide synthesis) and iv) the participation of immediate early genes in light-driven phase shifts. The present understanding of molecular timekeeping mechanism is exposed in light of the growing list of candidate clock-genes described within the SCN as well as in peripheral tissues of mammals and also in the clock-systems of phylogenetically lower species. Efferents from the SCN are also discussed with an interest toward understanding how the central circadian information is transmitted to the rest of the brain in order to impulse or/and coordinate the numerous rhythmic activities of the organism. Finally, cellular disturbances in peptide expression or content, reduction in the amplitude of a given functional index or even astrocytic proliferation are viewed along the line of pathologies observed with aging.

Afferent Pathways↗

Neurotoxic effects of neonatal injections of monosodium L-glutamate (L-MSG) on the retinal ganglion cell layer of the golden hamster: anatomical and functional consequences on the circadian system.

In rodents, daily injection of neurotoxic monosodium L-glutamate (MSG) during the postnatal period induces retinal lesions, optic nerve degeneration with an alteration of visual pathway and an absence of the b-wave in the electroretinogram. Despite this damage, electrophysiological responses subsist in the lateral geniculate bodies and synchronization of circadian rhythms to the light/dark cycle can still occur. Using two formal properties of the circadian system (entrainment and phase-shift by light), we assessed the functionality of retinal projections to the circadian clock in MSG-treated hamsters. Displaced amacrine and ganglion cell populations were quantified and retinal terminals in the suprachiasmatic nuclei were estimated. Animals received daily doses of glutamate during the first ten days after birth according to two protocols. The two treatments similarly destroyed 56% of the overall population of the ganglion cell layer: 30% of displaced amacrine and 89% of ganglion cells. Surviving ganglion neurons (7,500 cells) were evenly distributed across the entire retina except in one area of high cell density located in the temporoventral quadrant. Retinal projections of the "image-forming" pathway were drastically reduced in the dorsal lateral geniculate bodies, less in their ventral part. The "nonimage-forming" pathway was also affected since the volume of labeled terminals in the suprachiasmatic nuclei was reduced by one-half to one-third. Nevertheless, treated hamsters exhibited a free-running locomotor activity rhythm after several months in constant darkness, could be entrained by the light/dark cycle and phase-shifted by light pulses. These results suggest that a damaged retinohypothalamic tract can still assume the photic entrainment of the circadian clock.

Animals↗

Vomeronasal activation by urine in the primate Microcebus murinus: a 2 DG study.

The 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.

Animals↗

Deoxyglucose demonstration of in-utero hearing in the guinea pig foetus.

2-Deoxyglucose (2-[14C]DG) autoradiography was used to demonstrate central auditory function in the foetal guinea pig in-utero. The major advantage of this approach is that the experiment is carried out with the foetuses within the intact amniotic sac. Using pure tone stimuli at around 100 dB SPL, isofrequency bands of elevated metabolic activity were observed in the inferior colliculus of the majority of foetuses within the last 10 days of gestation.

Acoustic Stimulation↗

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.

Animals↗

Uncrossed and crossed inhibition in the inferior colliculus of the cat: a combined 2-deoxyglucose and electrophysiological study.

The cat inferior colliculus (IC) was studied with 2-deoxyglucose (2-DG). By presenting high-frequency tone bursts to one ear and white noise bursts simultaneously to the other, a band of reduced or inhibitory labeling was revealed in the central nucleus (ICC) of the IC ipsilateral to the ear receiving the tone bursts. It was concluded that this ipsilateral inhibition might be related to the organization of excitatory/inhibitory units in ICC. In the opposite ICC, narrow bands of increased labeling were seen. In some animals, the positions of single units were marked, and tone frequencies were presented under 2-DG, which were the same as these units' characteristic frequencies (CFs). The positions of the units coincided with the position of the inhibitory bands, indicating that they were functional isofrequency-inhibitory contours. Unlike higher auditory centers, the binaural inhibitory areas were in register with and not orthogonal to the excitatory isofrequency contours. The inhibitory contours were generally larger than the excitatory contours and became even larger in more caudal sections. Both the inhibitory and excitatory contours extended into dorsal cortex areas of IC. In two other cats, high-frequency tone bursts and white noise bursts were presented to the same ear, and both a band of increased and a band of reduced labelling were found in the IC contralateral to this ear. The inhibitory band was always lateral to the excitatory band and was often smaller. They did not become larger in more caudal sections. The position of a unit in one cat was marked by pontamine sky blue, and the position of the unit coincided with the position of the excitatory band. It was concluded that this lateral inhibitory band represents high-frequency inhibitory sidebands of cells with CFs lower than the stimulating tone. It is concluded that the 2-DG method might reveal hitherto unknown inhibitory systems if stimuli could be combined with diffuse stimuli that raised the general background activity of sensory systems.

Acoustic Stimulation↗

Decrease of [14C]2-deoxyglucose uptake at the intracerebellar nuclei during cerebellar cortex stimulation.

The effect of electrical stimulation of the cerebellar cortex at 10-30 c/s on metabolism in the intracerebellar nuclei has been studied using the [14C]2-deoxyglucose method. The experiments, performed on anesthetized or immobilized animals did not produce any detectable changes in the radioautographic labeling of the intracerebellar nuclei compared with controls. Experiments were also performed in animals pretreated with 3-acetylpyridine neurotoxin which selectively destroys the inferior olive and produces an intense labeling of the intracerebellar nuclei. Less marking was observed in restricted regions of the intracerebellar nuclei receiving the axon terminals of the stimulated Purkinje cells if the experiments were done within the first few hours. Following 3-acetylpyridine intoxication, in this early phase, destruction of the inferior olivary cell bodies occurs, but the climbing fibers remain intact. At 2 days or more following 3-acetylpyridine, changes in marking with stimulation could no longer be obtained. The finding is interpreted as being due to an actual reduction of the Purkinje cell activity upon stimulation of the cerebellar cortex, leading to a reduction of the metabolic activity at their presynaptic terminals.

Animals↗