Our scientific interests are focused on how molecular mechanisms contributing to the processing of inhibitory and excitatory inputs in neurons are integrated into neural circuits and determine affective, emotional behaviors.
In the laboratory, in particular, we concentrate on the intralaminar and midline thalamus (IL/MDLs), associative higher-order nuclei controlling emotional and attentional states and wake/sleep transitions, and on the epithalamic Medial Habenula (MHb), which controls aversion. The thalamus and the epithalamus are key hubs for the transfer of information between the anterior and the posterior brain. Although thalamus and epithalamus show a largely heterogeneous connectivity pattern, their circuital organization in rodents is simple and shows common features. Namely, no local circuitry is present in the vast majority of both thalamic and epithalamic subregions. Here, nuclei are indeed mostly composed of relay neurons that receive the incoming information and retransmit it without forming local collaterals. Information is thus processed at individual neuronal level by how cell firing patterns are affected by the incoming activity and by the activation of local molecular events. In this context, both the IL/MDLs and the MHb, and up/downstream areas, are endowed with unique (non)synaptic mechanisms contributing to information treatment.
For our research, we use a bottom-up approach. Starting from the analysis of both the morphological and the physiological organization and ex vivo properties of synaptic connections, our approaches extend to a comprehensive investigation of the in vivo behavioral outcomes elicited by interfering with identified molecular actors. To do this we apply state-of-the-art optogenetic and chemogenetic viral approaches in transgenic mouse models, in combination with more conventional morphological tools.
In recent years, our team provided important contributions in the domains of thalamic and medial habenular physiology. As an example, in the MHb our work led to the first demonstration of the existence of novel excitatory glycinergic NMDA receptors containing the unconventional GluN3A subunit. Our finding that these receptors are mandatory for the emergence of conditioned aversive states in adult mice (Otsu et al., Science, 2019) extended the spectrum of physiological functions associated with the typically inhibitory neurotransmitter glycine.
- Habenular Neurons Expressing Mu Opioid Receptors Promote Negative Affect in a Projection-Specific Manner.
Bailly J, Allain F, Schwartz E, Tirel C, Dupuy C, Petit F, Diana MA, Darcq E, Kieffer BL : Biol Psychiatry, 2022
- Astroglial Cx30 differentially impacts synaptic activity from hippocampal principal cells and interneurons.
Hardy E, Cohen-Salmon M, Rouach N, Rancillac A : Glia, 2021
- Adult medial habenula neurons require GDNF receptor GFRα1 for synaptic stability and function.
Fernández-Suárez D, Krapacher FA, Pietrajtis K, Andersson A, Kisiswa L, Carrier-Ruiz A, Diana MA, Ibáñez CF : PLoS Biol, 2021
- Neuropeptide S promotes wakefulness through the inhibition of sleep-promoting ventrolateral preoptic nucleus neurons.
Chauveau F, Claverie D, Lardant E, Varin C, Hardy E, Walter A, Canini F, Rouach N, Rancillac A : Sleep, 2020
- Cation-chloride cotransporters and the polarity of GABA signalling in mouse hippocampal parvalbumin interneurons.
Otsu Y, Donneger F, Schwartz EJ, Poncer JC : J Physiol, 2020
- Author Correction: Shifted pallidal co-release of GABA and glutamate in habenula drives cocaine withdrawal and relapse.
Meye FJ, Soiza-Reilly M, Smit T, Diana MA, Schwarz MK, Mameli M : Nat Neurosci, 2020
- Structural and functional connections between the median and the ventrolateral preoptic nucleus
Walter A, Van Der Spek L, Hardy E, Bemelmans A P, Rouach N, Rancillac A : Brain Structure and Function, 2019
- Reciprocal Regulation of KCC2 Trafficking and Synaptic Activity.
Côme E, Heubl M, Schwartz EJ, Poncer JC, Lévi S : Front Cell Neurosci, 2019
- Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula.
Otsu Y, Darcq E, Pietrajtis K, Mátyás F, Schwartz E, Bessaih T, Abi Gerges S, Rousseau CV, Grand T, Dieudonné S, Paoletti P, Acsády L, Agulhon C, Kieffer BL, Diana MA : Science, 2019
- Active intermixing of indirect and direct neurons builds the striatal mosaic.
Tinterri A, Menardy F, Diana MA, Lokmane L, Keita M, Coulpier F, Lemoine S, Mailhes C, Mathieu B, Merchan-Sala P, Campbell K, Gyory I, Grosschedl R, Popa D, Garel S : Nat Commun, 2018
- Functional Principles of Posterior Septal Inputs to the Medial Habenula.
Otsu Y, Lecca S, Pietrajtis K, Rousseau CV, Marcaggi P, Dugué GP, Mailhes-Hamon C, Mameli M, Diana MA : Cell Rep, 2018
- Unmasking GluN1/GluN3A excitatory glycine NMDA receptors.
Grand T, Abi Gerges S, David M, Diana MA, Paoletti P : Nat Commun, 2018