Jean-pierre Hornung | University of Lausanne (original) (raw)

Papers by Jean-pierre Hornung

Human Reproduction, 1996

The safety of microdrilling the zona pellucida of moose oocytes with a 1.48 |im diode laser has b... more The safety of microdrilling the zona pellucida of moose oocytes with a 1.48 |im diode laser has been investigated by determining the ability of mouse oocytes to fertilize in vitro and develop in vivo. Mice born after transfer of control and zona pelludda-microdrilled embryos into foster mothers were submitted to anatomical and immunohistochemical investigations, and their aptitude to breed was assessed in two subsequent generations. Decolonization of the oocytes with hyaluronidase induced a reduction of the fertilization and implantation rates, which was attributed to a zona hardening phenomenon. After laser zona pellucida microdrilling, these rates were restored to those obtained with embryos derived from untreated oocyte-cumulus complexes. Pups derived from zona pellucida microdrilled embryos were comparable with those obtained from control embryos, confirming the lack of deleterious effects of the laser treatment In conclusion, the 1.48 (un diode laser allows safe microdrilling of the zona pellucida of mouse oocytes after decoronization with hyaluronidase. Based on the health of the F 2 generation and the lack of neuroanatomical and neurochemical differences, we concluded that this technology may be investigated in the human, particularly when the zona pellucida represents the main impediment for fertilization or embryo hatching.

Schizophrenia Bulletin, 2005

The Journal of Neuroscience, 1984

Although cells in layer 4 of cat striate cortex represent the first stage in the cortical process... more Although cells in layer 4 of cat striate cortex represent the first stage in the cortical processing of visual information, they have considerably more complicated receptive field properties than the afferents to the layer from the lateral geniculate nucleus. In considering how these properties are generated, we have focused on the intrinsic cortical circuitry, and particularly on the projection to layer 4 from layer 6. Layer 6 pyramidal cells were injected with horseradish peroxidase and examined at the light and electron microscopic level. The labeled axon terminals were found to form asymmetric synapses and to show a strong preference for contacting dendritic shafts. Serial reconstruction of dendrites postsynaptic to labeled layer 6 cell axon terminals showed that a large proportion of the postsynaptic dendrites belonged to smooth and sparsely spiny stellate cells, suggesting a selective innervation of these cell types. In contrast, the geniculate projection to layer 4 made synapses primarily with dendritic spines and, as a result, the large majority of terminals ended on spiny cells. Since smooth and sparsely spiny stellate cells are thought to mediate inhibition within the cortex, we suggest that one effect of the layer 6 to layer 4 projection could be to contribute to inhibitory features of the receptive fields of layer 4 cells.

The Human Nervous System, 2012

PLoS Biology, 2009

The corpus callosum (CC) is the main pathway responsible for interhemispheric communication. CC a... more The corpus callosum (CC) is the main pathway responsible for interhemispheric communication. CC agenesis is associated with numerous human pathologies, suggesting that a range of developmental defects can result in abnormalities in this structure. Midline glial cells are known to play a role in CC development, but we here show that two transient populations of midline neurons also make major contributions to the formation of this commissure. We report that these two neuronal populations enter the CC midline prior to the arrival of callosal pioneer axons. Using a combination of mutant analysis and in vitro assays, we demonstrate that CC neurons are necessary for normal callosal axon navigation. They exert an attractive influence on callosal axons, in part via Semaphorin 3C and its receptor Neuropilin-1. By revealing a novel and essential role for these neuronal populations in the pathfinding of a major cerebral commissure, our study brings new perspectives to pathophysiological mechanisms altering CC formation.

The Human Nervous System, 2004

The raphe nuclei constitute a collection of cell groups distributed in the midline region of the ... more The raphe nuclei constitute a collection of cell groups distributed in the midline region of the tegmentum, from the rostral midbrain to the spinal cord transition at the pyramidal tract decussation. In the brain stem, the union of both sides along the midline region is underlined by the crossing of numerous tracts; the most prominent ones are the decussation of the superior cerebellar tract in the mesencephalon, and, in the medulla oblongata, the medial lemniscal and the corticospinal decussations. As a result, cell density in raphe nuclei varies greatly between regions, with sharp cytoarchitectonic boundaries for the dorsal raphe nucleus and ill-defined limits for the midline caudal nuclei. Collectively, the raphe nuclei are part of the reticular formation bordering the midline, and are referred to as the median division of the reticular formation. At variance to the other raphe nuclei, the dorsal raphe nucleus is located dorsal to the medial longitudinal fasciculus, in the ventral periaqueductal gray.

Science, 2006

Serotonin [5-hydroxytryptamine (5-HT)] neurotransmission in the central nervous system modulates ... more Serotonin [5-hydroxytryptamine (5-HT)] neurotransmission in the central nervous system modulates depression and anxiety-related behaviors in humans and rodents, but the responsible downstream receptors remain poorly understood. We demonstrate that global disruption of 5-HT2A receptor (5HT2AR) signaling in mice reduces inhibition in conflict anxiety paradigms without affecting fear-conditioned and depression-related behaviors. Selective restoration of 5HT2AR signaling to the cortex normalized conflict anxiety behaviors. These findings indicate a specific role for cortical 5HT2AR function in the modulation of conflict anxiety, consistent with models of cortical, “top-down” influences on risk assessment.

NeuroReport, 2000

for critically reviewing the manuscript, and to Dr J.M. Fritschy for the gift of the á1 and á5 GA... more for critically reviewing the manuscript, and to Dr J.M. Fritschy for the gift of the á1 and á5 GABA A receptor subunits. This work is presented by J.D. in part of the ful®llment of its medical doctoral degree at the University of Lausanne. This research was supported by the SNF grant 31-40852.94 and 31-50565.97. The early expression of neurotransmitters and receptors in the developing brain has brought attention to their potential contribution in modulating neuronal developmental processes. Monoamines are among the ®rst neurotransmitter systems to develop during embryogenesis. Depletion of neocortical serotonin or catecholamine afferents with selective neurotoxins resulted in a permanent alteration of the dendritic arborization of calretinin-containing interneurons, and a transient delay of parvalbumin and calbindin expression in a number of cortical neurones during the second postnatal week. The expression pattern of other developmentally regulated proteins, such as two subunits of the GABA A receptor, was not altered. Depletion of serotonin, and in part catecholamines, appeared to perturb several developmental processes of the cerebral cortex which would interfere with both its maturation and adult circuitry. NeuroReport 11:833±837 & 2000 Lippincott

Developmental Neurobiology, 2013

Experimental Brain Research, 1989

The CA (catecholamine/catecholaminergic) cell populations of the locus coeruleus (LC) and subcoer... more The CA (catecholamine/catecholaminergic) cell populations of the locus coeruleus (LC) and subcoeruleus (SubC) were studied using serial sections of the human brainstem immunostained with an antibody against tyrosine hydroxylase. The tyrosine hydroxylase-immunoreactive (TH-IR) neurons were plotted in a computer reconstruction system and their number and soma size determined. Serial section computer analysis was then used to create a three dimensional reconstruction of the LC complex. The number of cells containing neuromelanin pigment was also determined and compared with the number of TH-IR cells. In our sample there were 53,900 TH-IR cells in the LC and a further 6260 cells in the SubC. These numbers were very similar to our estimates of the number of cells containing neuromelanin pigment and we concluded that virtually all of these cells were also tyrosine hydroxylase positive. The average soma size of the TH-IR cells of the LC was 37 microns and in the SubC 34 microns. In addition to these quantitative observations the morphology of the TH-IR and the Nissl stained cells is described in some detail. We also compared the groups of immunoreactive cells in the human pons with the noradrenergic groups A5-A7 described in the rat. Although in the human these groups are contiguous, A5 is not part of the LC complex. However we did find that the A7 group is equivalent to the rostroventral part of SubC while the remainder of SubC is formed by ventral A6.

Journal of Anatomy

Human cadavers constitute very useful educational tools to teach anatomy in medical scholarship a... more Human cadavers constitute very useful educational tools to teach anatomy in medical scholarship and related disciplines such as physiology, for example. However, as biological material, human body is subjected to decay. Thanatopraxy cares such as embalming have been developed to slow down and inhibit this decay, but the formula used for the preservation fluids are mainly formaldehyde (FA)-based. Very recently, other formulas were developed in order to replace FA, and to avoid its toxicity leading to important environmental and professional exposure concerns. However, these alternative FA-free fluids are still not validated or commercialized, and their efficiency is still under discussion. In this context, the use of FA-releasing substances, already used in the cosmetics industry, may offer interesting alternatives in order to reduce professional exposures to FA. Simultaneously, the preservation of the body is still guaranteed by FA generated over time from FA-releasers. The aim of this review is to revaluate the use of FA in thanatopraxy cares, to present its benefits and disadvantages, and finally to propose an alternative to reduce FA professional exposure during thanatopraxy cares thanks to FA-releasers use.

Acta Neurobiologiae Experimentalis, 2003

6 1 Department of Fundamental Neurosciences, University of Lausanne, Rue du 7 Bugnon 9, CH-1005 L... more 6 1 Department of Fundamental Neurosciences, University of Lausanne, Rue du 7 Bugnon 9, CH-1005 Lausanne, Switzerland. 8 2 Department of Ophthalmology, University of Lausanne, Hôpital ophtalmique Jules9 Gonin, Av. de France 15, CH-1004 Lausanne, Switzerland. 10 3 Department of Psychiatry, Center for Psychiatric Neuroscience, Lausanne 11 University Hospital, Prilly, CH-1008 Lausanne, Switzerland. 12 13

Neuroscience Research, 2011

s / Neuroscience Research 71S (2011) e6–e44 e31 discovery science is the accrual of large-scale d... more s / Neuroscience Research 71S (2011) e6–e44 e31 discovery science is the accrual of large-scale deeply-phenotyped imaging datasets that can provide the necessary statistical power and phenotypic information upon which discovery can be carried out via sophisticated datamining, yielding novel insights into brain-behavior relationships and the complexities of the connectome. Simultaneously, the availability of largescale imaging datasets will quicken the development and translation of novel analytic techniques. The 1000 Functional Connectomes Project (FCP) invigorated the neuroimaging community by aggregating 1300 R-fMRI datasets independently collected by labs around the world, and making them publicly available. Initial analyses demonstrated the presence of a universal functional architecture across participants and sites, with stable loci of variation and significant sexand age-related difference among individuals. These findings, as well as those emerging from analysis of next-generation FCP data-sharing efforts, will be presented and discussed. Research funds: This research was partially supported by grants from NIMH R01MH081218, and the Stavros Niarchos Foundation (F.X.C.), and the Leon Levy Foundation. doi:10.1016/j.neures.2011.07.131 S3-G-1-1 Neuroscience education in Australia & New Zealand Sarah A. Dunlop Sch of Animal Biology, University of Western Australia, Australia Australian and New Zealand Universities (∼35) are diverse. Researchintensive Universities variously have medical Research Institutes, some being neuroscience-dedicated, or smaller neuroscience Centres. BSc neuroscience major degrees are offered at ∼1/3rd of Universities and are taught by diverse, rather than neuroscience-dedicated, Schools. High quality graduates may undertake a 1-year, research-intensive “Honours” program as a pre-requisite for a higher degree. Some Universities offer neuroscience Masters (2 years), combining course work and research. PhD programs (3–4 years) are currently full-time research. Research funding at early postdoctoral stages is highly competitive but becomes even more so mid-career. Australia has a senior Research Fellowship scheme through which some neuroscientists progress. The main source of research funding In Australia and New Zealand is government rather than philanthropic. However, whereas Australia has a relatively large number of research-only Fellowships, these are rare in New Zealand with neuroscience research and training being undertaken by academic (i.e. teaching and research) staff. The Australian Neuroscience Society (ANS) supports neuroscience education in high schools via the Australian & New Zealand Brain Bee Competition. ANS also trains 12 postgraduates per year in high-end electrophysiology and imaging techniques via its 3-week Australian Course in Advanced Neuroscience. Current changes in higher education include the introduction of broad-based cross-disciplinary degrees with a focus on professional workforce training. Specialization in disciplines such as neuroscience will still occur by Masters degrees and / or PhDs and combined course work and research PhDs are being mooted. The aging academic workforce will provide opportunities for PhDs in the medium term. The challenge is to provide short-to-medium term opportunities for early and mid-career researchers. doi:10.1016/j.neures.2011.07.132 S3-G-1-2 Supporting the training of master and doctoral neuroscience students across Europe Jean-Pierre Hornung DBCM, Fac Biol Medicine, Univ Lausanne, Lausanne, Switzerland In Europe, the educational system in each country, because of linguistic, cultural and economic differences, has developed diverse programs and criteria to acquire academic degrees. To favour mobility, 29 European countries signed in 1999 a declaration, which established standards in the academic degree levels and the amount of training by a standard number of credits. Neuroscience master and doctoral training programs, organized in Schools, formed since 2003 a Network (NENS) associated with FENS. Today around 160 programs in 28 countries are affiliated to NENS. NENS aims to promote higher education in the field of neuroscience and assist to the establishment of high quality standards in all countries across Europe. NENS has a complementary mission to the institutional and national programs to promote large scale international exchange and training activities. One major goal of NENS is to promote the mobility of the students. It effectively improves training by increasing their exposure to a broader academic and technical expertise. This could be achieved by either providing stipends for a short stay in a laboratory to practice a new technique or by favouring the development of international training programs. NENS should also promote student exchanges between Europe and other neuroscience communities in Asia or America during lab rotation in a Master or PhD program or lab visits in complement to the participation to a…

Scientific Reports

The homeodomain transcription factor Nkx2.1 (NK2 homeobox 1) controls cell differentiation of tel... more The homeodomain transcription factor Nkx2.1 (NK2 homeobox 1) controls cell differentiation of telencephalic GABAergic interneurons and oligodendrocytes. Here we show that Nkx2.1 also regulates astrogliogenesis of the telencephalon from embryonic day (E) 14.5 to E16.5. Moreover we identify the different mechanisms by which Nkx2.1 controls the telencephalic astrogliogenesis. In Nkx2.1 knockout (Nkx2.1 −/−) mice a drastic loss of astrocytes is observed that is not related to cell death. Further, in vivo analysis using BrdU incorporation reveals that Nkx2.1 affects the proliferation of the ventral neural stem cells that generate early astrocytes. Also, in vitro neurosphere assays showed reduced generation of astroglia upon loss of Nkx2.1, which could be due to decreased precursor proliferation and possibly defects in glial specification/differentiation. Chromatin immunoprecipitation analysis and in vitro co-transfection studies with an Nkx2.1-expressing plasmid indicate that Nkx2.1 binds to the promoter of glial fibrillary acidic protein (GFAP), primarily expressed in astrocytes, to regulate its expression. Hence, Nkx2.1 controls astroglial production spatiotemporally in embryos by regulating proliferation of the contributing Nkx2.1-positive precursors. Proper forebrain development is carried out by a series of coordinated and regulated events involving controlled cell proliferation, differentiation, and guided migration of neuronal and glial cells. Several spatiotemporally orchestrated molecular mechanisms underlie the successful patterning of the telencephalon 1-7. Both dorsal and ventral telencephalic regions are demarcated by specific gene expression patterns that then generate defined neuronal and glial populations. Dorsal progenitors express homeobox genes of the empty spiracles (Emx1/Emx2) and paired homeobox (Pax6) families, and the atonal-related genes Neurogenin (Neurog) 1/Neurog2, whereas the ventral progenitors are known to express homeobox genes of the Nkx (Nkx2.1) and distal-less (Dlx1/Dlx2) families, Gsh1/2, and achaete-scute-related gene Ascl1 8-12. Broadly, amongst the neuronal populations, the glutamatergic projection neurons are generated by dorsal telencephalic progenitors while the GABAergic (γ-aminobutyric acidergic) interneurons originate from the ventral telencephalic progenitors 3,13-15. Among the glial populations, embryonic oligodendrocytes are produced in waves from the ventral telencephalic progenitors 16,17. On the other hand, the exact timing of the generation and origin of the embryonic astroglial population is still a topic of active investigation. Since the astroglia play essential roles in guidance of forebrain commissures during embryonic brain development, a detailed understanding of the points of origin and exact timing of generation of the telencephalic astroglia is essential. In the ventral telencephalon, our and other reports have shown that early embryonic astrocytes are generated from ventral bipotential radial glia 18,19. In the dorsal telencephalon, especially the cerebral cortex, astrocyte gliogenesis has been documented to occur only after neurogenesis (after E17 in mice), when the bipotential radial glial cells of the dorsal pallium differentiate into glia precursors or astrocytes 20-29. Dorsal midline astroglia in the corpus callosum (CC), glial wedge (GW) and indusium griseum (IG) have also been shown to originate from the radial glia of the dorsomedial pallium 30,31. However, the time of generation of some of the astrocytes occupying the CC and adjacent regions is noted to be between E13 and postnatal day 2 (P2), with a peak at E14, much earlier than previously proposed 30. Later, the postnatal astrocytes that occupy the cerebral cortex region are believed to also originate

PLOS ONE

The calyx of Held, a large axo-somatic relay synapse containing hundreds of presynaptic active zo... more The calyx of Held, a large axo-somatic relay synapse containing hundreds of presynaptic active zones, is possibly the largest nerve terminal in the mammalian CNS. Studying its initial growth in-vitro might provide insights into the specification of synaptic connection size in the developing brain. However, attempts to maintain calyces of Held in organotypic cultures have not been fruitful in past studies. Here, we describe an organotypic slice culture method in which calyces of Held form in-vitro. We made coronal brainstem slices with an optimized slice angle using newborn mice in which calyces have not yet formed; the presynaptic bushy cells were genetically labeled using the Math5 promoter. After six to nine days of culturing, we readily observed large Math5-positive nerve terminals in the medial nucleus of the trapezoid body (MNTB), but not in the neighboring lateral superior olive nucleus (LSO). These calyx-like synapses expressed the Ca 2+-sensor Synaptotagmin-2 (Syt-2) and the Ca 2+ binding protein Parvalbumin (PV), two markers of developing calyces of Held in vivo. Application of the BMP inhibitor LDN-193189 significantly inhibited the growth of calyx synapses, demonstrating the feasibility of long-term pharmacological manipulation using this organotypic culture method. These experiments provide a method for organotypic culturing of calyces of Held, and show that the formation of calyx-like synapses onto MNTB neurons can be preserved in-vitro. Furthermore, our study adds pharmacological evidence for a role of BMP-signaling in the formation of large calyx of Held synapses.

Journal of Pain and Symptom Management