Exposure to aversive events during sensitive developmental periods can affect the preferential coping strategy adopted by individuals later in life, leading to either stress-related psychiatric disorders, including depression, or to well-adaptation to future adversity and sources of stress, a behavior phenotype termed “resilience”. We have previously shown that interfering with the development of mother-pups bond with the Repeated Cross Fostering (RCF) stress protocol can induce resilience to depression-like phenotype in adult C57BL/6J female mice. Here, we used patch-clamp recording in midbrain slice combined with both in vivo and ex vivo pharmacology to test our hypothesis of a link between electrophysiological modifications of dopaminergic neurons in the intermediate Ventral Tegmental Area (VTA) of RCF animals and behavioral resilience. We found reduced hyperpolarization-activated (Ih) cation current amplitude and evoked firing in VTA dopaminergic neurons from both young and adult RCF female mice. In vivo, VTA-specific pharmacological manipulation of the Ih current reverted the pro-resilient phenotype in adult early-stressed mice or mimicked behavioral resilience in adult control animals. This is the first evidence showing how pro-resilience behavior induced by early events is linked to a long-lasting reduction of Ih current and excitability in VTA dopaminergic neurons.
Resilience to anhedonia-passive coping induced by early life experience is linked to a long-lasting reduction of Ih current in VTA dopaminergic neurons: altered Ih current in the VTA of adult resilient-to-depression mice / D'Addario, S. L.; Di Segni, M.; Ledonne, A.; Piscitelli, R.; Babicola, L.; Martini, A.; Spoleti, E.; Mancini, C.; Ielpo, D.; D'Amato, F. R.; Andolina, D.; Ragozzino, D.; Mercuri, N. B.; Cifani, C.; Renzi, M.; Guatteo, E.; Ventura, R.. - In: NEUROBIOLOGY OF STRESS. - ISSN 2352-2895. - 14:(2021). [10.1016/j.ynstr.2021.100324]
Resilience to anhedonia-passive coping induced by early life experience is linked to a long-lasting reduction of Ih current in VTA dopaminergic neurons: altered Ih current in the VTA of adult resilient-to-depression mice
D'Addario S. L.Co-primo
;Di Segni M.Co-primo
;Ledonne A.;Piscitelli R.;Babicola L.;Ielpo D.;Andolina D.;Ragozzino D.;Renzi M.;Ventura R.
2021
Abstract
Exposure to aversive events during sensitive developmental periods can affect the preferential coping strategy adopted by individuals later in life, leading to either stress-related psychiatric disorders, including depression, or to well-adaptation to future adversity and sources of stress, a behavior phenotype termed “resilience”. We have previously shown that interfering with the development of mother-pups bond with the Repeated Cross Fostering (RCF) stress protocol can induce resilience to depression-like phenotype in adult C57BL/6J female mice. Here, we used patch-clamp recording in midbrain slice combined with both in vivo and ex vivo pharmacology to test our hypothesis of a link between electrophysiological modifications of dopaminergic neurons in the intermediate Ventral Tegmental Area (VTA) of RCF animals and behavioral resilience. We found reduced hyperpolarization-activated (Ih) cation current amplitude and evoked firing in VTA dopaminergic neurons from both young and adult RCF female mice. In vivo, VTA-specific pharmacological manipulation of the Ih current reverted the pro-resilient phenotype in adult early-stressed mice or mimicked behavioral resilience in adult control animals. This is the first evidence showing how pro-resilience behavior induced by early events is linked to a long-lasting reduction of Ih current and excitability in VTA dopaminergic neurons.File | Dimensione | Formato | |
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