title: Footshock-induced plasticity of GABABsignalling in the lateral habenula requires dopamine and glucocorticoid receptors.
abstract: The activity of lateral habenula (LHb) represents a substrate for the encoding of negative-valenced events. The exposure to aversive stimuli in naïve mice is sufficient to trigger a reduction in GABAB-mediated signaling in the LHb. This is ultimately instrumental for the hyperactivity of LHb neurons and for the establishment of depressive-like phenotypes. However, the mechanisms responsible for the induction of this aversion-driven plasticity are missing. Using ex-vivo patch-clamp recordings in slices, here we show that exposing mice to a series of inescapable footshocks (FsE) rapidly reduces baclofen-mediated GABABcurrents in the LHb. This plasticity of GABABsignaling requires the activation of the dopamine and stress pathways. Indeed, the systemic administration of dopamine and glucocorticoids receptor antagonists prevents the FsE-induced reduction of GABABcurrents in the LHb. To test whether the recruitment of these receptors occurs within the LHb, we exposed slices from control mice to either dopamine or corticosterone. Both manipulations failed to alter the amplitudes of baclofen-mediated GABABcurrents. Altogether, these data suggest that dopamine and stress signaling are necessary for the induction of FsE-evoked GABABplasticity in the LHb. However, the activation of these specific receptors may occur in structures different than the LHb, suggesting a circuit-based mechanism for this form of plasticity. These findings provide mechanistic insights on aversion-driven plasticity within the LHb.
authors.affiliation: Institut du Fer à Moulin, Paris, France.|Institut national de la santé et de la recherche médicale, UMR-S 839, Paris, France.|Université Pierre et Marie Curie Paris, France.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Lecca
authors.affiliation: Institut du Fer à Moulin, Paris, France.|Institut national de la santé et de la recherche médicale, UMR-S 839, Paris, France.|Université Pierre et Marie Curie Paris, France.
authors.forename: Massimo
authors.initials: M
authors.lastname: Trusel
authors.affiliation: Institut du Fer à Moulin, Paris, France.|Institut national de la santé et de la recherche médicale, UMR-S 839, Paris, France.|Université Pierre et Marie Curie Paris, France.
authors.forename: Manuel
authors.initials: M
authors.lastname: Mameli
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology; D019262:Habenula / Q000378:metabolism* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity; D011954:Receptors, Dopamine / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: D058786:GABA-B Receptor Agonists; D011954:Receptors, Dopamine; D018080:Receptors, GABA-B; D011965:Receptors, Glucocorticoid; D001418:Baclofen
keywords: GABA; aversion; dopamine; glucocorticoids; habenula