Mild stress accumulation limits GABAergic synaptic plasticity in the lateral habenula. (3rd January 2022)

• Record Type: Journal Article
• Authors: Lalive, Arnaud L.; Nuno‐Perez, Alvaro; Tchenio, Anna; Mameli, Manuel
• Is Part Of: European journal of neuroscience. Volume 55:Number 2(2022)
• Page Start: 377
• Page End: 387
• Publication Date: 2022-01-03
• Subjects: inhibitory transmission -- long‐term depression -- nitric oxide -- presynaptic release -- stress; Nervous system -- Periodicals; 612.8
• DOI: 10.1111/ejn.15581
• Languages: English
• ISSNs: 0953-816X

Abstract

Abstract: Animals can cope with isolated stressful situations without enduring long‐term 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 GABAB 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. Abstract : Neuronal depolarization induces long‐term depression of GABA (GABA LTD), but not glutamate transmission in the LHb. GABA LTD is induced postsynaptically and expressed presynaptically via nitric oxide as a retrograde messenger and GABAB receptors. Exposure to single mild stressors (novelty or social isolation) does not affect GABA LTD, but their accumulation prevents the expression of the plasticity.