PhD Scientific Days 2019

Budapest, April 25–26, 2019

Chemogenetic activation of GABAergic neurons in the bed nucleus of stria terminalis during memory consolidation impairs extinction of fear memory

Bíró, László

Laszlo Biro1,2, Bruzsik Biborka1,2, Huba Szebik1, Dora Zelena3, Cintia Finszter1, Eszter Sipos3, Klara R. Sarosdi1, Orsolya Horvath1, Imre Farkas4, Veronika Csillag4, Eva Mikics1, Mate Toth1
1Laboratory of Translational Behavioural Neuroscience, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
2 Janos Szentagothai Doctoral School of Neurosciences, Semmelweis University, Budapest
3 Laboratory of Behavioral and Stress Studies, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary
4 Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary

Language of the presentation

Hungarian

Text of the abstract

Introduction: Consolidation of fearful memories is canonically attributed to the prefrontal cortex, basolateral amygdala and ventral hippocampal network. Formation of extinction-resistant fear memory and its generalization to other contexts are still poorly understood, despite constituting the core symptomatology of several anxiety disorders. The bed nucleus of stria terminalis (BNST) belongs to the aforementioned neuronal network of interconnected limbic regions, suggesting its integrative modulatory role in fear memory formation and anxiety-related behaviors. BNST consists of mainly GABAergic neurons (vGAT+) expressing different neuropeptides such as corticotrophin-related factor (CRF+) and somatostatin (SOM+), but it is unknown how these cells modulate fear memory processes.
Aims: We aimed to explore the involvement of genetically defined BNST cell populations in the consolidation of conditioned fear memory and in the expression of anxiety-related behaviors.
Method: We expressed stimulatory and inhibitory DREADDs (designer receptors exclusively activated by a designer drug) in either vGAT+, CRF+ or SOM+ neurons of the BNST. We tested whether stimulation or inhibition of vGAT+ neurons interferes with conditioned fear memory consolidation after cued auditory fear conditioning or affects innate anxiety in the open-field test.
Results: Stimulation of vGAT+ neurons enhanced fear recall and caused an anxiogenic effect. Manipulation of CRF+ neurons neither had any effect on fear recall nor anxiety-related behavior. Stimulation of SOM+ cells in the BNST during memory consolidation increased fear generalization and impaired fear extinction.
Conclusion: Our results provide insight how aberrant neuronal activity in a subcortical structure could contribute to the emergence of extinction-resistant fear memory genesis.

Data of the presenter

Doctoral School: Neurosciences
Program: Neuroendocrinology
Supervisor: Eva Mikics
Email: biro.laszlo@koki.mta.hu