Mild stress accumulation limits GABAergic synaptic plasticity in the lateral habenula

Arnaud L Lalive (1) , Alvaro Nuno‐perez (1) , Anna Tchenio (1) , Manuel Mameli (1, 2)

1 Department of Fundamental Neurosciences, [University of Lausanne]
2 IFM - Inserm U1270 - SU - Institut du Fer à Moulin

Animals can cope with isolated stressful situations without enduring longterm consequences. However, when exposure to stressors becomes recurrent, behavioural symptoms of anxiety and depression can emerge. Yet, the neuronal mechanisms governing responsivity to isolated stressor remain elusive. Here, we investigate synaptic adaptations following mild stress in the lateral habenula (LHb), a structure engaged in aversion encoding and dysfunctional in depression. We describe that neuronal depolarization in the LHb drives long-term depression of inhibitory, but not excitatory, synaptic transmission (GABA LTD). This plasticity requires nitric oxide and presynaptic GABA B receptors, leading to a decrease in probability of GABA release. Mild stressors such as brief social isolation, or exposure to novel environment in the company of littermates, do not alter GABA LTD. In contrast, GABA LTD is absent after mice experience a novel environment in social isolation. Altogether, our results suggest that LHb GABAergic plasticity is sensitive to stress accumulation, which could represent a threshold mechanism for long-term alterations of LHb function.

Mots clés: inhibitory transmission; long-term depression; nitric oxide; presynaptic release; stress

Domaines: Neurosciences [q-bio.NC]

Arnaud L Lalive, Alvaro Nuno‐perez, Anna Tchenio, Manuel Mameli. Mild stress accumulation limits GABAergic synaptic plasticity in the lateral habenula. European Journal of Neuroscience, 2022, ⟨10.1111/ejn.15581⟩. ⟨hal-03519051⟩