Biomedical subjects

F Varoqueaux

Publications and source records attributed to F Varoqueaux.

8 recordsLinked to original sources

PubMed2001

Complexins regulate a late step in Ca2+-dependent neurotransmitter release.

Synaptic vesicle fusion at synapses is triggered by increases in cytosolic Ca2+ levels. However, the identity of the Ca2+ sensor and the transduction mechanism of the Ca2+ trigger are unknown. We show that Complexins, stoichiometric components of the exocytotic core complex, are important regulators of transmitter release at a step immediately preceding vesicle fusion. Neurons lacking Complexins show a dramatically reduced transmitter release efficiency due to decreased Ca2+ sensitivity of the synaptic secretion process. Analyses of mutant neurons demonstrate that Complexins are acting at or following the Ca2+-triggering step of fast synchronous transmitter release by regulating the exocytotic Ca2+ sensor, its interaction with the core complex fusion machinery, or the efficiency of the fusion apparatus itself.

Adaptor Proteins, Vesicular Transport↗

PubMed2000

Munc13-1 acts as a priming factor for large dense-core vesicles in bovine chromaffin cells.

In chromaffin cells the number of large dense-core vesicles (LDCVs) which can be released by brief, intense stimuli represents only a small fraction of the 'morphologically docked' vesicles at the plasma membrane. Recently, it was shown that Munc13-1 is essential for a post-docking step of synaptic vesicle fusion. To investigate the role of Munc13-1 in LDCV exocytosis, we overexpressed Munc13-1 in chromaffin cells and stimulated secretion by flash photolysis of caged calcium. Both components of the exocytotic burst, which represent the fusion of release-competent vesicles, were increased by a factor of three. The sustained component, which represents vesicle maturation and subsequent fusion, was increased by the same factor. The response to a second flash, however, was greatly reduced, indicating a depletion of release-competent vesicles. Since there was no apparent change in the number of docked vesicles, we conclude that Munc13-1 acts as a priming factor by accelerating the rate constant of vesicle transfer from a pool of docked, but unprimed vesicles to a pool of release-competent, primed vesicles.

Animals↗

PubMed1999

Hormonal regulation of glutamate receptor gene expression in the anteroventral periventricular nucleus of the hypothalamus.

Glutamate plays an important role in mediating the positive feedback effects of ovarian steroids on gonadotropin secretion, and the preoptic region of the hypothalamus is a likely site of action of glutamate. The anteroventral periventricular nucleus (AVPV) of the preoptic region is an essential part of neural pathways mediating hormonal feedback on gonadotropin secretion, and it appears to provide direct inputs to gonadotropin releasing hormone (GnRH)-containing neurons. Immunohistochemistry and in situ hybridization were used in this study to define the distribution and hormonal regulation of glutamate receptor subtypes in the AVPV of juvenile female rats. Neurons that express the NMDAR1 receptor subtype are abundant in the AVPV, as are cells that express AMPA receptor subtypes (GluR1, GluR2, and GluR3 but not GluR4), and the AVPV appears to contain a dense plexus of NMDAR1-immunoreactive presynaptic terminals. However, AVPV neurons do not seem to express detectable levels of kainate receptor (GluR5, GluR6, and GluR7) or metabotropic receptor (mGluR1-6) subtypes. Treatment of ovariectomized juvenile rats with estradiol induced expression of GluR1 mRNA but did not alter levels of GluR2 or GluR3 mRNA. Treatment of estrogen-primed ovariectomized juvenile rats with progesterone caused an initial increase in GluR1 mRNA expression, followed by a small decrease 24 hr after treatment. In contrast, estrogen appears to suppress levels of NMDAR1 mRNA in the AVPV, which remained unchanged after progesterone treatment. Thus, one mechanism whereby ovarian steroids may provide positive feedback to GnRH neurons is by altering the sensitivity of AVPV neurons to glutamatergic activation.

Animals↗

PubMed1999

Projections of the mediolateral part of the lateral septum to the hypothalamus, revealed by Fos expression and axonal tracing in rats.

The lateral septum participates in a variety of functions involving the hypothalamus. The present study investigated the effect of an electrical stimulation of the mediolateral part of the lateral septum on the expression of Fos in the hypothalamic nuclei by using immunohistochemical methods in anaesthetised and free-moving rats. We analysed in another series of rats the direct projections of the lateral septum by axonal anterograde tracing with biotinylated dextran-amine. Tracing was used in combination with Fos labelling in a third series of animals. Stimulation induced an expression of Fos in neurones located in anteroventral and anterodorsal preoptic nuclei, medial preoptic area, anterior hypothalamic nucleus, subparaventricular zone, dorsomedial nucleus, lateral hypothalamic area and mammillary nucleus. The distribution of Fos-immunoreactive neurones conforms to the topographic organisation of direct projections from the lateral septum, as revealed by axonal tracing. These results suggest that the lateral septum activates definite hypothalamic structures by a direct link. Some structures displayed substantial Fos labelling whereas they received a slight, or no projection, from the lateral septum. This was particularly evident in the core of the ventromedial nucleus and in areas known to contain tubero-infundibular neurones. This observation suggests that the lateral septum may also exert an indirect control, via polysynaptic links, on hypothalamic structures including nuclei involved in neuroendocrine mechanisms.

Animals↗

PubMed1998

Dual (excitatory and inhibitory) calretinin innervation of AMPA receptor-containing neurons in the rat lateral septum.

A recent study demonstrated both an extrinsic and an intrinsic calretinin (CR) innervation of the rat septal complex and that a population of the extrinsic calretinin fibers is aspartate/glutamate-containing. The aim of this study was to determine which types (GluR1, GluR2/3, or both) of AMPA receptor-containing lateral septal area neurons are innervated by extrinsic and intrinsic CR neurons and whether the intrinsic CR cells are GABAergic. Light- and electron-microscopic single immunostaining for CR, GluR1, and GluR2/3, as well as light- and electron-microscopic-double immunostaining experiments for CR plus GluR1 and CR plus GluR2/3 were performed in the lateral septal area. Furthermore, the "mirror" colocalization technique was employed on consecutive vibratome sections of the septal complex to investigate whether the intrinsic septal CR neurons are GABAergic. The results are summarized as follows: (1) both GluR1- and GluR2/3-immunoreactive neurons are innervated by CR-containing fibers; (2) the majority of these synapses, observed mainly on the soma and, to a lesser extent, on proximal dendrites of AMPA receptor-containing neurons, represent asymmetric synaptic membrane specializations; (3) a minority of CR-containing axon terminals associated with both GluR1- and GluR2/3-immunoreactive neurons form symmetric contacts, predominantly on their soma; and (4) 93% of the lateral septal area CR cells are GABAergic. These observations indicate that both GluR1- and GluR2/3-containing lateral septal area neurons receive a dual intrinsic and extrinsic CR innervation. The former (intrinsic) CR boutons are GABAergic, while the latter form asymmetric synaptic contacts, are excitatory, and probably originate in the supramammillary area, since previous work has demonstrated that a population of supramammillo-septal fibers contain aspartate and/or glutamate.

Animals↗

PubMed1997

Hypothalamo-septal enkephalinergic fibers terminate on AMPA receptor-containing neurons in the rat lateral septal area.

A large number of septal neurons express alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA)-type excitatory glutamate receptors. It has been demonstrated that in the mediolateral part of the rat lateral septum, calbindin-containing neurons are heavily innervated by hypothalamic, enkephalinergic fibers forming exclusively asymmetric synaptic contacts. This connection was suggested to be excitatory. In order to further elucidate this hypothesis, the aim of the present study was to determine whether these enkephalinoceptive neurons express GluR1 and GluR2/3 AMPA receptor subunits. Correlated light and electron microscopic analysis, using single immunostaining for GluR1 and GluR2/3, and double immunostaining for Leu-enkephalin and GluR1 or GluR2/3, was performed on vibratome sections of the rat lateral septal area. The studies revealed that while GluR1 is mainly associated with dendritic and somatic spines, GluR2/3 is mostly present in the perisomatic area. Leu-enkephalin boutons establish asymmetric synaptic contacts at the level of the soma and initial dendrites of both of these cells. A semiquantitative analysis showed that these enkephalin-targeted cells represent 50% of the total number of both GluR1 and GluR2/3-containing lateral septal neurons. These results suggest that: (1) AMPA receptor-expressing neurons appear to be the exclusive recipient of hypothalamic Leu-enkephalin boutons; (2) these enkephalinoceptive neurons contain both GluR1 and GluR2/3 AMPA receptor subunits; however, (3) only the GluR2/3 subtype, located in the perisomatic area, may be associated with Leu-enkephalin-containing inputs.

Animals↗

PubMed1997

Neurochemical characterization of AMPA receptor-containing neurons in the mediolateral septal area of the rat.

The lateral septum receives a massive innervation by excitatory amino acid-containing limbic cortical and hypothalamic afferents, and previous studies have described a wide distribution of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor-containing neurons in this area. The aim of this study was to determine whether different subtypes of AMPA receptors are expressed in the same neurons. Furthermore, considering the fact that a population of lateral septal cells, the "somatospiny neurons," are GABAergic calbindin-containing cells, the coexistence of each subtype of AMPA receptor with calbindin was also investigated. Colocalization experiments were performed on adjacent vibratome sections of the lateral septal area for GluR1 and GluR2/3 AMPA-receptor subunits, GluR1 and calbindin, GluR2/3 and calbindin, as well as GluR1 plus calbindin and GluR2/3 plus calbindin, using the "mirror" colocalization technique. The results are summarized as follows: (1) GluR1 is present in the soma and most intensively expressed in dendrites and somatic and dendritic spines; while GluR2/3 is associated with the soma and proximal dendrites of the neurons. (2) Forty-one percent of the AMPA receptor-containing neurons cocontain GluR1 and GluR2/3. (3) Thirty-eight percent of GluR1- and 28% of GluR2/3-labeled cells express calbindin. (4) Sixty-two percent of the calbindin-immunoreactive neurons contain GluR1 and 51% of them express GluR2/3. (5) Half of the neurons expressing both GluR1 and GluR2/3 also contain calbindin. (6) The distribution of GluR1 plus GluR2/3-containing, GluR1 plus calbindin-containing, and GluR2/3 plus calbindin-containing neurons in the lateral septum are homogeneous. This study indicates the existence of multiple populations of AMPA receptor- and calbindin-containing neurons in the lateral septal area.

Animals↗

PubMed1994

Lateral septal projections onto tubero-infundibular neurons in the hypothalamus of the guinea pig.

Efferent projections of the lateral septal nucleus (LS) to the preoptic area and the hypothalamus were identified in 20 female guinea pigs after iontophoretic injection of the anterograde axonal tracer Fluoro-Ruby. Tubero-infundibular (TI) neurons of the preoptic area and the hypothalamus were retrogradely labeled after intracardiac injection of Granular Blue or Fluoro-Gold. Magnocellular neurons of the supraoptic and paraventricular nuclei were also labeled. The double labeling procedure allowed an estimation of the extent of the direct relationship between LS efferents and TI neurons. Contacts between lateral septal fibers and TI cell bodies were mainly observed at the light-microscopical level in the preoptic area. A group of labeled fibers coursing along the third ventricle established sparse connections with hypothalamic periventricular TI neurons. A few appositions was observed in the infundibular (arcuate) nucleus, suggestive of a monosynaptic regulation of TI neurons by a septo-arcuate tract. Close association with labeled magnocellular neurons was also noted at the edge of the supraoptic and paraventricular nuclei. The sparse but direct connections between LS and TI neurons may be involved in the neuroendocrine functions of the LS.

Animals↗