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Synaptic mechanisms underlying behaviour induced by social isolation in adolescent mice

English title Synaptic mechanisms underlying behaviour induced by social isolation in adolescent mice
Applicant Bellone Camilla
Number 182326
Funding scheme Project funding (Div. I-III)
Research institution Dépt des Neurosciences Fondamentales Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurophysiology and Brain Research
Start/End 01.10.2018 - 30.09.2022
Approved amount 904'000.00
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Keywords (3)

Dopamine; social behaviour; Reward system

Lay Summary (Italian)

Lead
Studio dei meccanismi sinaptici alla base di comportamenti aberranti indotti da isolamento sociale durante l'adolescenza in topi
Lay summary

L'adolescenza rappresenta un periodo critico per lo sviluppo delle funzioni sociali sia nell’uomo che nell’animale. Infatti, mentre il gioco e’ fondamentale per assicurare lo sviluppo del comportamento sociale, episodi di stress legati alla sfera sociale hanno ripercussioni drammatiche sulla socialita’. Il sistema della ricompensa e in particolare i neuroni dopaminergici della Area Tegmentale Ventrale codificano per specifici aspetti della socialita’. Usando tecniche di elettrofisiologia sia in vivo che in vitro, analisi di complessi comportamenti sociali e manipolazioni di circuiti cerebrali nei topi, studieremo come brevi perodi di isolamento sociale durante l’adolescenza possano provocare specifiche alterazioni in definite popolazioni neuronali. Poiche îsolamento sociale ha un forte impatto sullo sviluppo di malattie psichiatirche, l’identificationi di meccanismi cellulari in definiti network potrebbe contribuire a identificare nuovi target terapeutici. 

 

Direct link to Lay Summary Last update: 08.10.2018

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Abstract

Converging lines of evidence in human indicate that social environment during adolescence influences the development of adult social behaviour. During this period, the social environment changes dramatically since the focus of interaction shifts from parents to peers and the individual learns the social rules that will use through the entire life. Mouse models have a crucial value to investigate the influence of social environment. Indeed, mice are social animals. For example, social approach, social motivation, social avoidance, social dominance and aggression, are different aspects of social behaviours that can be monitored and dissected at biological level in mice using behavioural paradigms. Social behaviours in rodents as in human follow a very precise development pattern and adolescence represents a very sensitive period. Indeed, while play behaviour, particularly in males, is relevant to ensure social behaviour pattern that will then develop later in life, social stressors may substantially alter this developmental profile. Therefore, the experience of and the reaction to positive or negative social stimuli during this period will promote social approach or avoidance behaviours in adulthood. Mice are sensitive to social isolation (SI) and an age-dependent effect of isolation on subsequent social behaviours has been described. For example short-term isolation in juvenile mice enhances social interests (rebound sociability), increases the incentive values for social contacts and modulates defensive and avoidance behaviours (Arakawa, 2017). The mechanisms and the circuits underlying the effect of SI during adolescence on social approach and avoidance behaviours are still largely unknown. Data in the literature suggest that Dopamine (DA) neurons of the Ventral Tegmental Area (VTA) encode specific information on social behaviour. Indeed, the activity of VTA DA neurons encodes information on social novelty exploration. Importantly it has been shown that deprivation of social stimuli during adolescence in rats enhances synaptic plasticity of glutamatergic transmission onto the VTA but whether these changes are accompanied by a modification in DA neuronal circuit and causally linked to subsequent changes in social behaviours has not been investigated,Using ex vivo and in vivo physiology combined with optogenetic and chemogenetic tools and behavioral paradigms in mice we propose to:Aim 1: Characterize SI-induced social behavioursAim 2: Investigate the synaptic mechanisms underlying SI-induced social behavioursAim 3: Deconstruct the midbrain circuits underlying SI-induced social behaviours SignificanceSocial environment modulates the progression of neurodevelopmental disorders, such as Autism Spectrum Disorders, Schizophrenia and Depression. While social enrichment generally ameliorates the symptoms, social isolation, defined as a deprivation of social contact and interaction, impairs social and cognitive functions. Unravelling the underlying neural mechanism may reveal novel targets for rational therapies.
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