Biology subjects

Balado, E.

Publications and source records attributed to Balado, E..

3 recordsLinked to original sources

bioRxiv2023

Sex-dependent effects of stress on insular cortex-to-nucleus accumbens synaptic plasticity

Stress is an important risk factor for the development of psychiatric disorders and men and women tend to react differently to stress. Sex differences are also observed in many stress-related psychiatric disorders such as depression, anxiety disorders or addiction. Therefore, identifying specific neuroadaptations induced by stress, in males and females, is a necessary step to the understanding of stress-related sex dimorphism in these disorders. Here, we tested the hypotheses that acute stress could affect plasticity in the anterior insular cortex (aIC)-nucleus accumbens core (NAcC) pathway, two structures involved in the stress response, in a sex-dependent manner. Using in vivo extracellular recordings in anesthetized rats, we show that synaptic plasticity in the aIC-NAcC pathway is different between male and female rats. Whereas in males, long-term potentiation and long-term depression were equally induced, in females, there was mostly a long-term potentiation induced. Moreover, stress affected synaptic plasticity in the aIC-NAcC differently in male and female rats. In males, stress induced a loss of long-term-depression that lasted for at least 24h, whereas in females, stress induced less neurons displaying LTP, which did not last. These results demonstrate that integration of aIC information to NAcC is different between males and females. This study provides mechanistic support for differential reactivity to stress between males and females that may relate to stress-related psychiatric disorders and sex dimorphism in these disorders.

neuroscience↗

bioRxiv2022

Complex social behaviour during an extended period of time in a valproic acid animal model of autism spectrum disorder.

Autism Spectrum Disorder (ASD) is a progressive neurodevelopmental disorder characterized mainly by deficits in social communication and stereotyped and restricted interests. Deficits in social interactions in ASD animal models are generally analysed using the three chambers test paradigm that is simple to implement and use but fails to detect subtle social deficits or complex social behavior on an extended period of time within a group of mice. Here, we set up a novel procedure entitled the Live Mouse Tracker (LMT) that detects a great number of complex social behaviours that we recorded continuously for up to three days in groups of 4 mice. This was performed in the valproic acid (VPA) mouse model where VPA (450 mg/kg) was injected to pregnant females at E12.5. Studies were performed with a special focus on females given that ASD is 3-4 times more diagnosed in males than in females and that several ASD models failed to detect major social deficits in females, contrary to males. Comparisons were made within groups of 4 female animals with same treatment or within groups of different treatments (saline versus VPA). We report that VPA females show several types of social deficits and that are different in nature and magnitude in relation with time (from 1 hour to 3 days). These deficits were also different when VPA mice were tested together compared to when they were mixed with saline treated mice. Indeed, while social behavior was improved in VPA mice with the presence of saline mice that of saline mice was negatively affected by the presence of VPA mice. This study indicates that female VPA mice show several social deficits, contrary to the common knowledge. It further implies that ASD related behavior alters normal behavior in a mixed group of mice.

neuroscience↗

bioRxiv2022

Premorbid performances determine the deleterious effects of nigrostriatal degeneration and pramipexole on behavioural flexibility

Subtle cognitive impairment can occur early in the course of Parkinsons disease (PD) and may manifest under different forms of executive dysfunction such as impaired cognitive flexibility. The precise contribution of nigrostriatal dopaminergic neurodegeneration to these non-motor features of the disease is poorly known. Whether such cognitive impairment associated with the disease process may also predate and contribute to the development of neuropsychiatric side-effects following dopamine replacement therapy remains largely unknown. To address these issues, we investigated the respective contributions of nigrostriatal degeneration and chronic treatment with the dopamine D3-preferring agonist pramipexole on behavioural flexibility in a rat model of PD. Flexible, intermediate and inflexible rats were identified based on baseline assessment of behavioural flexibility using an operant set-shifting task. Nigrostriatal degeneration was induced by bilateral viral-mediated expression of A53T mutated human -synuclein in the substantia nigra pars compacta and behavioural flexibility was assessed after induction of nigrostriatal degeneration, and during chronic pramipexole treatment. Nigrostriatal degeneration impaired behavioural flexibility in flexible but not in inflexible rats. Pramipexole induced a decrease of behavioural flexibility that was exacerbated in lesioned rats and in the most flexible individuals. Furthermore, the deficits induced by pramipexole in lesioned rats affected different components of the task between flexible and inflexible individuals. This study demonstrates that nigrostriatal degeneration and pramipexole unequally impair behavioural flexibility, suggesting that the susceptibility to develop non-motor impairments upon treatment initiation could primarily depend on premorbid differences in behavioural flexibility.

neuroscience↗