Sex differences in amygdalohippocampal oscillations and neuronal activation in a rodent anxiety model and in response to infralimbic deep brain stimulation

IntroductionDepression and anxiety are highly comorbid mental disorders with marked sex differences. Both disorders show altered activity in the amygdala, hippocampus, and prefrontal cortex. Infralimbic deep brain stimulation (DBS-IL) has anxiolytic and antidepressant effects, but the underlying mec...

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Main Authors: Hanna Vila-Merkle, Alicia González-Martínez, Rut Campos-Jiménez, Joana Martínez-Ricós, Vicent Teruel-Martí, Ana Lloret, Arantxa Blasco-Serra, Ana Cervera-Ferri
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Behavioral Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnbeh.2023.1122163/full
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author Hanna Vila-Merkle
Alicia González-Martínez
Rut Campos-Jiménez
Joana Martínez-Ricós
Vicent Teruel-Martí
Ana Lloret
Arantxa Blasco-Serra
Ana Cervera-Ferri
author_facet Hanna Vila-Merkle
Alicia González-Martínez
Rut Campos-Jiménez
Joana Martínez-Ricós
Vicent Teruel-Martí
Ana Lloret
Arantxa Blasco-Serra
Ana Cervera-Ferri
author_sort Hanna Vila-Merkle
collection DOAJ
description IntroductionDepression and anxiety are highly comorbid mental disorders with marked sex differences. Both disorders show altered activity in the amygdala, hippocampus, and prefrontal cortex. Infralimbic deep brain stimulation (DBS-IL) has anxiolytic and antidepressant effects, but the underlying mechanisms remain unclear. We aimed to contribute to understanding sex differences in the neurobiology of these disorders.MethodsIn male and female rats, we recorded neural oscillations along the dorsoventral axis of the hippocampus and the amygdala in response to an anxiogenic drug, FG-7142. Following this, we applied DBS-IL.ResultsSurprisingly, in females, the anxiogenic drug failed to induce most of the changes observed in males. We found sex differences in slow, delta, theta, and beta oscillations, and the amygdalo-hippocampal communication in response to FG-7142, with modest changes in females. Females had a more prominent basal gamma, and the drug altered this band only in males. We also analyzed c-Fos expression in both sexes in stress-related structures in response to FG-7142, DBS-IL, and combined interventions. With the anxiogenic drug, females showed reduced expression in the nucleus incertus, amygdala, septohippocampal network, and neocortical levels. In both experiments, the DBS-IL reversed FG-7142-induced effects, with a more substantial effect in males than females.DiscussionHere, we show a reduced response in female rats which contrasts with the higher prevalence of anxiety in women but is consistent with other studies in rodents. Our results open compelling questions about sex differences in the neurobiology of anxiety and depression and their study in animal models.
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spelling doaj.art-89052e17ace64e46b06073b6ab19f0e82023-02-23T09:14:42ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532023-02-011710.3389/fnbeh.2023.11221631122163Sex differences in amygdalohippocampal oscillations and neuronal activation in a rodent anxiety model and in response to infralimbic deep brain stimulationHanna Vila-Merkle0Alicia González-Martínez1Rut Campos-Jiménez2Joana Martínez-Ricós3Vicent Teruel-Martí4Ana Lloret5Arantxa Blasco-Serra6Ana Cervera-Ferri7Neuronal Circuits Laboratory, Department of Human Anatomy and Embryology, Faculty of Medicine, University of Valencia, Valencia, SpainNeuronal Circuits Laboratory, Department of Human Anatomy and Embryology, Faculty of Medicine, University of Valencia, Valencia, SpainNeuronal Circuits Laboratory, Department of Human Anatomy and Embryology, Faculty of Medicine, University of Valencia, Valencia, SpainNeuronal Circuits Laboratory, Department of Human Anatomy and Embryology, Faculty of Medicine, University of Valencia, Valencia, SpainNeuronal Circuits Laboratory, Department of Human Anatomy and Embryology, Faculty of Medicine, University of Valencia, Valencia, SpainDepartment of Physiology, Faculty of Medicine, Health Research Institute INCLIVA, CIBERFES, University of Valencia, Valencia, SpainStudy Group for the Anatomical Substrate of Pain and Analgesia (GESADA) Laboratory, Department of Human Anatomy and Embryology, Faculty of Medicine and Odontology, University of Valencia, Valencia, SpainNeuronal Circuits Laboratory, Department of Human Anatomy and Embryology, Faculty of Medicine, University of Valencia, Valencia, SpainIntroductionDepression and anxiety are highly comorbid mental disorders with marked sex differences. Both disorders show altered activity in the amygdala, hippocampus, and prefrontal cortex. Infralimbic deep brain stimulation (DBS-IL) has anxiolytic and antidepressant effects, but the underlying mechanisms remain unclear. We aimed to contribute to understanding sex differences in the neurobiology of these disorders.MethodsIn male and female rats, we recorded neural oscillations along the dorsoventral axis of the hippocampus and the amygdala in response to an anxiogenic drug, FG-7142. Following this, we applied DBS-IL.ResultsSurprisingly, in females, the anxiogenic drug failed to induce most of the changes observed in males. We found sex differences in slow, delta, theta, and beta oscillations, and the amygdalo-hippocampal communication in response to FG-7142, with modest changes in females. Females had a more prominent basal gamma, and the drug altered this band only in males. We also analyzed c-Fos expression in both sexes in stress-related structures in response to FG-7142, DBS-IL, and combined interventions. With the anxiogenic drug, females showed reduced expression in the nucleus incertus, amygdala, septohippocampal network, and neocortical levels. In both experiments, the DBS-IL reversed FG-7142-induced effects, with a more substantial effect in males than females.DiscussionHere, we show a reduced response in female rats which contrasts with the higher prevalence of anxiety in women but is consistent with other studies in rodents. Our results open compelling questions about sex differences in the neurobiology of anxiety and depression and their study in animal models.https://www.frontiersin.org/articles/10.3389/fnbeh.2023.1122163/fullanxietydepressiondeep brain stimulationhippocampusamygdalabrain oscillations
spellingShingle Hanna Vila-Merkle
Alicia González-Martínez
Rut Campos-Jiménez
Joana Martínez-Ricós
Vicent Teruel-Martí
Ana Lloret
Arantxa Blasco-Serra
Ana Cervera-Ferri
Sex differences in amygdalohippocampal oscillations and neuronal activation in a rodent anxiety model and in response to infralimbic deep brain stimulation
Frontiers in Behavioral Neuroscience
anxiety
depression
deep brain stimulation
hippocampus
amygdala
brain oscillations
title Sex differences in amygdalohippocampal oscillations and neuronal activation in a rodent anxiety model and in response to infralimbic deep brain stimulation
title_full Sex differences in amygdalohippocampal oscillations and neuronal activation in a rodent anxiety model and in response to infralimbic deep brain stimulation
title_fullStr Sex differences in amygdalohippocampal oscillations and neuronal activation in a rodent anxiety model and in response to infralimbic deep brain stimulation
title_full_unstemmed Sex differences in amygdalohippocampal oscillations and neuronal activation in a rodent anxiety model and in response to infralimbic deep brain stimulation
title_short Sex differences in amygdalohippocampal oscillations and neuronal activation in a rodent anxiety model and in response to infralimbic deep brain stimulation
title_sort sex differences in amygdalohippocampal oscillations and neuronal activation in a rodent anxiety model and in response to infralimbic deep brain stimulation
topic anxiety
depression
deep brain stimulation
hippocampus
amygdala
brain oscillations
url https://www.frontiersin.org/articles/10.3389/fnbeh.2023.1122163/full
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