Neurocentre Magendie

Delphine GIRARD


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3 publication(s) depuis Décembre 2013:

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05/2017 | Eur J Neurosci   IF 2.9
Species-specific diversity in the anatomical and physiological organisation of the BNST-VTA pathway.
Kaufling J, Girard D, Maitre M, Leste-Lasserre T, Georges F

The anteromedial part of the bed nucleus of the stria terminalis (amBNST) is a limbic structure innervating the ventral tegmental area (VTA) that is remarkably constant across species. The amBNST modulates fear and anxiety, and activation of VTA dopamine (DA) neurons by amBNST afferents seems to be the way by which stress controls motivational states associated with reward or aversion. Because fear learning and anxiety states can be expressed differently between rats and mice, we compared the functional connectivity between amBNST and the VTA-DA neurons in both species using consistent methodological approaches. Using a combination of in vivo electrophysiological, neuroanatomical tracing and laser capture approaches we explored the BNST influences on VTA-DA neuron activity. First, we characterised in rats the molecular phenotype of the amBNST neurons projecting to the VTA. We found that this projection is complex, including both GABAergic and glutamatergic neurons. Then, VTA injections of a conventional retrograde tracer, the beta-sub-unit of the cholera toxin (CTB), revealed a stronger BNST-VTA projection in mice than in rats. Finally, electrical stimulations of the BNST during VTA-DA neuron recording demonstrated a more potent excitatory influence of the amBNST on VTA-DA neuron activity in rats than in mice. These data illustrate anatomically, but also functionally, a significant difference between rats and mice in the amBNST-VTA pathway. More generally, together with previous findings, our research highlights the importance of species differences for the interpretation and the generalisation of research data.

20/02/2017 | Nat Commun   IF 12.1
NMDA-receptor-dependent plasticity in the bed nucleus of the stria terminalis triggers long-term anxiolysis.
Glangetas C, Massi L, Fois GR, Jalabert M, Girard D, Diana M, Yonehara K, Roska B, Xu C, Luthi A, Caille S, Georges F

Anxiety is controlled by multiple neuronal circuits that share robust and reciprocal connections with the bed nucleus of the stria terminalis (BNST), a key structure controlling negative emotional states. However, it remains unknown how the BNST integrates diverse inputs to modulate anxiety. In this study, we evaluated the contribution of infralimbic cortex (ILCx) and ventral subiculum/CA1 (vSUB/CA1) inputs in regulating BNST activity at the single-cell level. Using trans-synaptic tracing from single-electroporated neurons and in vivo recordings, we show that vSUB/CA1 stimulation promotes opposite forms of in vivo plasticity at the single-cell level in the anteromedial part of the BNST (amBNST). We find that an NMDA-receptor-dependent homosynaptic long-term potentiation is instrumental for anxiolysis. These findings suggest that the vSUB/CA1-driven LTP in the amBNST is involved in eliciting an appropriate response to anxiogenic context and dysfunction of this compensatory mechanism may underlie pathologic anxiety states.

11/12/2013 | J Neurosci   IF 6
Stress switches cannabinoid type-1 (CB1) receptor-dependent plasticity from LTD to LTP in the bed nucleus of the stria terminalis.
Glangetas C, Girard D, Groc L, Marsicano G, Chaouloff F, Georges F

The bed nucleus of the stria terminalis (BNST) exerts a coordinated modulation of the psychoneuroendocrine responses to stress. However, how acute stress impacts on BNST in vivo plasticity is a crucial question that still remains unanswered. Here, neurons from the anterior portion of the BNST (aBNST) were recorded in vivo during and after stimulation of their medial prefrontal cortical (mPFC) afferents. In C57BL/6N mice, a 1 h restraint stress induced a switch from long-term depression (LTD) to long-term potentiation (LTP) in the aBNST after a 10 Hz mPFC stimulation. This switch was independent from glucocorticoid receptor stimulation. Because the endocannabinoid system regulates aBNST activity, we next examined the role of cannabinoid type-1 receptors (CB1-Rs) in these changes. Mutant mice lacking CB1-Rs (CB1(-/-) mice) displayed a marked deficit in the ability to develop plasticity under control and stress conditions, compared with their wild-type littermates (CB1(+/+) mice). This difference was not accounted for by genetic differences in stress sensitivity, as revealed by Fos immunohistochemistry analyses. Local blockade of CB1-Rs in the aBNST and the use of mutant mice bearing a selective deletion of CB1-Rs in cortical glutamatergic neurons indicated that stress-elicited LTP involved CB1-Rs located on aBNST excitatory terminals. These results show that acute stress reverts LTD into LTP in the aBNST and that the endocannabinoid system plays a key role therein.