Biomedical subjects

Gilles Gheusi

Publications and source records attributed to Gilles Gheusi.

7 recordsLinked to original sources

PubMed2004

Nicotinic receptors regulate the survival of newborn neurons in the adult olfactory bulb.

Cholinergic axons and nicotinic receptors are abundant in all layers of the olfactory bulb (OB), the main region of newborn neuron integration in the adult brain. Here, we report that the OB granule cell layer in mice lacking the predominant form of brain high-affinity nicotinic acetylcholine receptors (beta(2)(-/-) mice) displayed nearly 50% more newborn neurons and significantly fewer apoptotic cells than did beta(2)(+/+) mice. Conversely, in vivo chronic nicotine exposure significantly decreased the number of newborn granule cells in beta(2)(+/+) but not beta(2)(-/-) adult mice, confirming that the survival of newborn neurons can be controlled by the activation of beta(2)-containing nicotinic acetylcholine receptors. Unexpectedly, investigating the behavioral consequence of an increased number of granule cells in beta(2)(-/-) mice revealed that these animals have a less robust short-term olfactory memory than their wild-type counterparts. Taken together, these results provide evidence that high-affinity nicotinic receptors are involved in the maturation of adult OB local circuits. They also indicate that an increase in the number of granule cells does not necessarily correlate with better olfactory performance and further highlight the importance of cholinergic afferents for olfactory processing.

Aging↗

PubMed2003

Olfactory processing in a changing brain.

The perception of odorant molecules provides the essential information that allows animals to explore their surrounding. We describe here how the external world of scents may sculpt the activity of the first central relay of the olfactory system, i.e., the olfactory bulb. This structure is one of the few brain areas to continuously replace one of its neuronal populations: the local GABAergic interneurons. How the newly generated neurons integrate into a pre-existing neural network and how basic olfactory functions are maintained when a large percentage of neurons are subjected to continuous renewal, are important questions that have recently received new insights. Furthermore, we shall see how the adult neurogenesis is specifically subjected to experience-dependent modulation. In particular, we shall describe the sensitivity of the bulbar neurogenesis to the activity level of sensory inputs from the olfactory epithelium and, in turn, how this neurogenesis may adjust the neural network functioning to optimize odor information processing. Finally, we shall discuss the behavioral consequences of the bulbar neurogenesis and how it may be appropriate for the sense of smell. By maintaining a constitutive turnover of bulbar interneurons subjected to modulation by environmental cues, we propose that adult ongoing neurogenesis in the olfactory bulb is associated with improved olfactory memory. These recent findings not only provide new fuel for the molecular and cellular bases of sensory perception but should also shed light onto cellular bases of learning and memory.

Animals↗

PubMed2003

Social regulation of reproduction in the female mound-builder mouse (Mus spicilegus).

Social environment influences the reproductive physiology and sexual behaviour of the female house mouse Mus musculus. An all-female environment tends to suppress the oestrous cycles, whereas the presence of a male induces and synchronises sexual receptivity. However, reproductive responses to social environment may differ among the various species of rodents. In mound-builder female mice, Mus spicilegus, periods of sexual receptivity are interrupted by periods where adult females display a vaginal closure. We investigated the influence of different social environments on the vaginal opening and oestrous state of adult female M. spicilegus. Result showed that when females were grouped their vaginas were generally closed but that vaginal opening occurred when they were isolated or housed with a sexual partner. Females became sexually receptive when housed with a male, but when isolated their cervical smears did not reach characteristics of the oestrus. In female M. spicilegus, male presence thus has a stimulating effect on oestrous induction. Furthermore, cohabitation with females has an inhibiting effect on vaginal opening.

Animals↗

PubMed2002

Enriched odor exposure increases the number of newborn neurons in the adult olfactory bulb and improves odor memory.

In the mammalian forebrain, most neurons originate from proliferating cells in the ventricular zone lining the lateral ventricles, including a discrete area of the subventricular zone (SVZ). In this region, neurogenesis continues into adulthood. Most of the cells generated in the SVZ are neuronal precursors with progeny that migrate rostrally along a pathway known as the rostral migratory stream before they reach the main olfactory bulb (MOB) where they differentiate into local interneurons. The olfactory system thus provides an attractive model to investigate neuronal production and survival, processes involving interplay between genetic and epigenetic influences. The present study was conducted to investigate whether exposure to an odor-enriched environment affects neurogenesis and learning in adult mice. Animals housed in either a standard or an odor-enriched environment for 40 d were injected intraperitoneally with bromodeoxyuridine (BrdU) to detect proliferation among progenitor cells and to follow their survival in the MOB. The number of BrdU-labeled neurons was not altered 4 hr after a single BrdU injection. In contrast, the number of surviving progenitors 3 weeks after BrdU injection was markedly increased in animals housed in an enriched environment. This effect was specific because enriched odor exposure did not influence hippocampal neurogenesis. Finally, we showed that adult mice housed in odor-enriched cages display improved olfactory memory without a change in spatial learning performance. By maintaining a constitutive turnover of granule cells subjected to modulation by environmental cues, ongoing bulbar neurogenesis could be associated with improved olfactory memory.

Administration, Inhalation↗

PubMed2002

[Neurogenesis in the adult brain. Functional consequences].

In the adult mammalian brain, neuroblasts are continuously produced within the subgranular zone of the hippocampus and the subventricular zone (SVZ) of the forebrain. In this review we describe how some physiological and environmental factors play important roles in regulating neurogenesis in the hippocampus. Neuroblasts in the SVZ network migrate rostrally into the olfactory bulb where they differentiate into local interneurons. We focus on the production, survival and functional consequences of these newly generated interneurons. We show that enriched odor-exposure enhances the number of newborn neurons in the adult olfactory bulb but not in the hippocampus. This effect did not result from changes in cell proliferation but rather was due to greater neuronal survival. Furthermore, the enriched condition was found to dramatically extend the olfactory memory. By maintaining a constitutive turnover of interneurons subjected to regulation by bulbar activity, ongoing neurogenesis plays a key role in olfactory memory.

Adult↗

PubMed1998

Molecular basis of sickness behavior.

Peripheral and central injections of lipopolysaccharide (LPS), a cytokine inducer, and recombinant proinflammatory cytokines such as interleukin-1 beta (IL-1 beta) induce sickness behavior in the form of reduced food intake and decreased social activities. Mechanisms of the behavioral effects of cytokines have been the subject of much investigation during the last 3 years. At the behavioral level, the profound depressing effects of cytokines on behavior are the expression of a highly organized motivational state. At the molecular level, sickness behavior is mediated by an inducible brain cytokine compartment that is activated by peripheral cytokines via neural afferent pathways. Centrally produced cytokines act on brain cytokine receptors that are similar to those characterized on peripheral immune and nonimmune cells, as demonstrated by pharmacologic experiments using cytokine receptor antagonists, neutralizing antibodies to specific subtypes of cytokine receptors, and gene targeting techniques. Evidence exists that different components of sickness behavior are mediated by different cytokines and that the relative importance of these cytokines is not the same in the peripheral and central cytokine compartments.

Animals↗

PubMedDate not supplied

Making scents of olfactory neurogenesis.

Olfaction was long considered to belong more to the realm of art than to that of science. As a result, how the brain perceives, discriminates, and recognizes odorant molecules is still a mystery. Recent progress has nonetheless been made at early stages of the olfactory pathway when olfactory studies entered into the molecular era to elucidate the first contact of an odor molecule with a receptor. Our group focuses on the analysis of odor information in the olfactory bulb, the first processing relay in the mammalian brain. Using this model, we are attempting to decipher the code for odorant information. Furthermore, the olfactory bulb also provides an attractive model to investigate neuronal proliferation, differentiation, migration, and neuronal death, processes involving an interplay between genetic and epigenetic influences. Finally, our goal is to explore the possible consequences of the olfactory bulb plasticity, in olfactory performance. For these purposes, we aim to combine morphological, electrophysiological and behavioral approaches to investigate: (1) how the olfactory bulb processes odor molecule information, (2) how neural precursors differentiate into olfactory bulb interneurons, (3) how these newly-generated neurons integrate into an operational neural network, (4) what role they play in the adult olfactory bulb, and (5) how are basic olfactory functions maintained in such a sensory system subjected to continuous renewal of a large percentage of its neuronal population. These questions should provide new fuel for the molecular and cellular bases of sensory perception and shed light onto cellular bases of learning and memory.

Animals↗