Investigando fenótipos comportamentais e eletrofisiológicos associados ao estresse social

The aims of this thesis were to investigate behavioral and electrophysiological patterns associated to resilience and susceptibility to social stress in mice. For this, we used a chronic social defeat stress protocol based on the resident-intruder paradigm. The results are presented here in two st...

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Autor principal: Alves, Aron de Miranda Henriques
Outros Autores: Queiroz, Cláudio Marcos Teixeira de
Formato: doctoralThesis
Idioma:por
Publicado em: Brasil
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Endereço do item:https://repositorio.ufrn.br/jspui/handle/123456789/21620
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id ri-123456789-21620
record_format dspace
institution Repositório Institucional
collection RI - UFRN
language por
topic Approach-avoidance conflict
Social defeat
Defensive behaviors
Ethoexperimental analysis
Anhedonia
Sucrose-preference
Psychiatric disorders
CNPQ::OUTROS::CIENCIAS: NEUROCIÊNCIAS
spellingShingle Approach-avoidance conflict
Social defeat
Defensive behaviors
Ethoexperimental analysis
Anhedonia
Sucrose-preference
Psychiatric disorders
CNPQ::OUTROS::CIENCIAS: NEUROCIÊNCIAS
Alves, Aron de Miranda Henriques
Investigando fenótipos comportamentais e eletrofisiológicos associados ao estresse social
description The aims of this thesis were to investigate behavioral and electrophysiological patterns associated to resilience and susceptibility to social stress in mice. For this, we used a chronic social defeat stress protocol based on the resident-intruder paradigm. The results are presented here in two studies. In the first study, C57BL/6J mice submitted to repeated social defeat episodes showed delayed motivation to interact with an unfamiliar conspecific in long duration (10 min) sessions of the social interaction test. By using an ethological approach combined with computational video analysis, it was possible to track precisely the mouse position during social investigation behavior performance. With that approach, it was analyzed the detailed expression of defensive behaviors, such as stretched attended postures and flights, both associated to social investigation behaviors. From these analyzes, it was demonstrated that social investigation behaviors based on stretched attend postures were significantly higher in defeated mice in comparison to controls. Still, a subpopulation of defeated mice showed persistently and non-habituating stretched attend postures during social investigation. By using a measure based on the investigation distance during social investigations, it was possible to compute an approach index (AI) to each animal and separate a subpopulation showing an anxiety-related phenotype. The flight incidence was also increased in defeated group as compared with controls. The persistent occurrence of this behavior was observed in a subpopulation of defeated mice. We calculated a flight index (FI) that inversely correlated with sucrose preference, showing to be useful to identify anhedonic animals. In the second study, we combined ethological approach and electrophysiological recordings in the ventral tegmental area of mice submitted to chronic social defeat stress. By using electrophysiological and pharmacological criteria, single-units recorded from the ventral tegmental area were classified as putative dopaminergic and non-dopaminergic neurons. During the social investigation behavior it was observed that firing rate modulations of distinct neuronal subpopulations occurred in opposite manner in social defeat susceptible and resilient mice. In summary, this work proposes that longer sessions of the social interaction test associated to ethological approach can provide information for the behavioral classifications of resilient and susceptible mice after social defeat stress. Furthermore, the expression of susceptible phenotype could be related to the midbrain dopaminergic system impairment in the incentive value assignment to social interactions normally associated with increased mesolimbic neuronal activity.
author2 Queiroz, Cláudio Marcos Teixeira de
author_facet Queiroz, Cláudio Marcos Teixeira de
Alves, Aron de Miranda Henriques
format doctoralThesis
author Alves, Aron de Miranda Henriques
author_sort Alves, Aron de Miranda Henriques
title Investigando fenótipos comportamentais e eletrofisiológicos associados ao estresse social
title_short Investigando fenótipos comportamentais e eletrofisiológicos associados ao estresse social
title_full Investigando fenótipos comportamentais e eletrofisiológicos associados ao estresse social
title_fullStr Investigando fenótipos comportamentais e eletrofisiológicos associados ao estresse social
title_full_unstemmed Investigando fenótipos comportamentais e eletrofisiológicos associados ao estresse social
title_sort investigando fenótipos comportamentais e eletrofisiológicos associados ao estresse social
publisher Brasil
publishDate 2017
url https://repositorio.ufrn.br/jspui/handle/123456789/21620
work_keys_str_mv AT alvesarondemirandahenriques investigandofenotiposcomportamentaiseeletrofisiologicosassociadosaoestressesocial
_version_ 1773957535491948544
spelling ri-123456789-216202017-11-04T00:40:54Z Investigando fenótipos comportamentais e eletrofisiológicos associados ao estresse social Alves, Aron de Miranda Henriques Queiroz, Cláudio Marcos Teixeira de http://lattes.cnpq.br/1531296839709463 http://lattes.cnpq.br/3384801391828521 Laplagne, Diego Andres http://lattes.cnpq.br/0293416967746987 Quadros, Isabel Marian Hartmann de http://lattes.cnpq.br/3982014468609862 Leão, Richardson Naves http://lattes.cnpq.br/0683942077872227 Figuerola, Wilfredo Blanco http://lattes.cnpq.br/9912829629195282 Approach-avoidance conflict Social defeat Defensive behaviors Ethoexperimental analysis Anhedonia Sucrose-preference Psychiatric disorders CNPQ::OUTROS::CIENCIAS: NEUROCIÊNCIAS The aims of this thesis were to investigate behavioral and electrophysiological patterns associated to resilience and susceptibility to social stress in mice. For this, we used a chronic social defeat stress protocol based on the resident-intruder paradigm. The results are presented here in two studies. In the first study, C57BL/6J mice submitted to repeated social defeat episodes showed delayed motivation to interact with an unfamiliar conspecific in long duration (10 min) sessions of the social interaction test. By using an ethological approach combined with computational video analysis, it was possible to track precisely the mouse position during social investigation behavior performance. With that approach, it was analyzed the detailed expression of defensive behaviors, such as stretched attended postures and flights, both associated to social investigation behaviors. From these analyzes, it was demonstrated that social investigation behaviors based on stretched attend postures were significantly higher in defeated mice in comparison to controls. Still, a subpopulation of defeated mice showed persistently and non-habituating stretched attend postures during social investigation. By using a measure based on the investigation distance during social investigations, it was possible to compute an approach index (AI) to each animal and separate a subpopulation showing an anxiety-related phenotype. The flight incidence was also increased in defeated group as compared with controls. The persistent occurrence of this behavior was observed in a subpopulation of defeated mice. We calculated a flight index (FI) that inversely correlated with sucrose preference, showing to be useful to identify anhedonic animals. In the second study, we combined ethological approach and electrophysiological recordings in the ventral tegmental area of mice submitted to chronic social defeat stress. By using electrophysiological and pharmacological criteria, single-units recorded from the ventral tegmental area were classified as putative dopaminergic and non-dopaminergic neurons. During the social investigation behavior it was observed that firing rate modulations of distinct neuronal subpopulations occurred in opposite manner in social defeat susceptible and resilient mice. In summary, this work proposes that longer sessions of the social interaction test associated to ethological approach can provide information for the behavioral classifications of resilient and susceptible mice after social defeat stress. Furthermore, the expression of susceptible phenotype could be related to the midbrain dopaminergic system impairment in the incentive value assignment to social interactions normally associated with increased mesolimbic neuronal activity. Os objetivos desta tese foram os de investigar padrões comportamentais e eletrofisiológicos associados à resiliência e suscetibilidade ao estresse social induzido em camundongos. Para isso, utilizamos um protocolo de indução de estresse crônico contínuo a partir de derrotas sociais baseado no paradigma residente-intruso. Os resultados da tese são apresentados em dois estudos. No primeiro estudo, camundongos C57BL/6J submetidos a episódios repetidos de derrota social apresentaram motivação tardia para interagir com um camundongo desconhecido em sessões prolongadas (10 min) do teste de interação social. Utilizando uma abordagem etológica associada à análise computacional de vídeos foi possível rastrear precisamente a posição dos camundongos durante a realização de comportamentos de investigação social. Analisamos ainda a expressão detalhada de comportamentos defensivos, tais como investigação em postura estendida e fugas, ambos associados ao comportamento de investigação social. A partir dessas análises demonstramos que a realização do comportamento de investigação social em postura estendida era significativamente maior para o grupo derrotado comparado ao grupo controle. Ainda, um subgrupo de camundongos derrotados apresentou investigação social em postura estendida de forma persistente e sem habituação. Utilizando uma medida da distância de investigação durante as investigações sociais calculamos um índice de aproximação (IA) para cada animal e separamos um subgrupo apresentando fenótipo relacionado à ansiedade. A incidência de fugas também foi maior no grupo derrotado em comparação com os controles. A persistência na ocorrência desse comportamento foi observada em um subgrupo de camundongos submetidos às derrotas sociais. Calculamos então um índice de fugas (IF) que se correlacionou inversamente com a preferência por sacarose, sendo útil para identificar animais anedônicos. No segundo estudo, foram combinados análise etológica e registros eletrofisiológicos com tetrodos na área tegmentar ventral de camundongos submetidos à derrotas sociais. Utilizando critérios eletrofisiológicos e farmacológicos classificamos unidades na área tegmentar ventral como supostos neurônios dopaminérgicos e não-dopaminérgicos. Durante o comportamento de investigação social foi observado que a modulação da taxa de disparo dessas subpopulações neuronais distintas ocorreu de maneira oposta em animais suscetíveis e resilientes ao estresse social. Em suma, propomos que sessões prolongadas associadas à análise etológica detalhada durante os testes de interação social podem prover informação para classificação de camundongos em resilientes e susceptíveis após repetidas derrotas sociais. Ainda, a expressão do fenótipo suscetível parece estar associada ao comprometimento do sistema dopaminérgico mesolímbico na atribuição de valor de incentivo às interações sociais normalmente associadas ao aumento da atividade neuronal mesolímbica. 2017-01-12T10:50:01Z 2017-01-12T10:50:01Z 2015-12-16 doctoralThesis ALVES, Aron de Miranda Henriques. Investigando fenótipos comportamentais e eletrofisiológicos associados ao estresse social. 2015. 92f. Tese (Doutorado em Neurociências) - Universidade Federal do Rio Grande do Norte, Universidade Federal do Rio Grande do Norte, Natal, 2015. https://repositorio.ufrn.br/jspui/handle/123456789/21620 por Acesso Aberto application/pdf Brasil UFRN PROGRAMA DE PÓS-GRADUAÇÃO EM NEUROCIÊNCIAS