RESUMO
Basal amygdala (BA) neurons projecting to nucleus accumbens (NAc) core/shell are primarily glutamatergic and are integral to the circuitry of emotional processing. Several recent mouse studies have addressed whether neurons in this population(s) respond to reward, aversion or both emotional valences. The focus has been on processing of physical emotional stimuli, and here, we extend this to salient social stimuli. In male mice, an iterative study was conducted into engagement of BA-NAc neurons in response to estrous female (social reward, SR) and/or aggressive-dominant male (social aversion, SA). In BL/6J mice, SR and SA activated c-Fos expression in a high and similar number/density of BA-NAc neurons in the anteroposterior intermediate BA (int-BA), whereas activation was predominantly by SA in posterior (post-)BA. In Fos-TRAP2 mice, compared with SR-SR or SA-SA controls, exposure to successive presentation of SR-SA or SA-SR, followed by assessment of tdTomato reporter and/or c-Fos expression, demonstrated that many int-BA-NAc neurons were activated by only one of SR and SA; these SR/SA monovalent neurons were similar in number and present in both magnocellular and parvocellular int-BA subregions. In freely moving BL/6J mice exposed to SR, bulk GCaMP6 fibre photometry provided confirmatory in vivo evidence for engagement of int-BA-NAc neurons during social and sexual interactions. Therefore, populations of BA-NAc glutamate neurons are engaged by salient rewarding and aversive social stimuli in a topographic and valence-specific manner; this novel evidence is important to the overall understanding of the roles of this pathway in the circuitry of socio-emotional processing.
Assuntos
Complexo Nuclear Basolateral da Amígdala , Núcleo Accumbens , Proteína Vermelha Fluorescente , Camundongos , Masculino , Feminino , Animais , Núcleo Accumbens/metabolismo , Ácido Glutâmico/metabolismo , Neurônios/fisiologia , RecompensaRESUMO
Learning adaptive behaviour to control aversion is a major brain function. Detecting the absence of control is also important, although chronic uncontrollable aversion can impact maladaptively on stimulus processing in general. The mouse basomedial amygdala (BMA) contributes to aversion processing with high BMA activity associated with active behavioural responding. The overall aim of the present study was to investigate the associations between aversion (un)controllability, BMA activity and behaviour. Fibre photometry of GCaMP6-expressing BMA neuron populations was applied in freely behaving adult male mice during exposure to mild electrical shocks, and effects of specific or general (un)controllability were investigated. In a discrete learned helplessness (LH) effect paradigm, mice underwent discrete sessions of pre-exposure to either escapable shock (ES) or inescapable shock (IES) followed by an escape test. IES mice acquired fewer escape attempts than ES mice, and this co-occurred with higher aversion-related BMA activity in the IES group. After 30 days, ES and IES mice were allocated equally to either chronic social stress (CSS)-exposure to continuous uncontrollable social aversion-or control handling (CON), and on days 5 and 15 underwent an IES session. CSS mice made fewer escape attempts than CON mice, and this was now associated with lower aversion-related BMA activity in the CSS group. These findings suggest that mouse BMA activity is higher when discrete aversion is uncontrollable but becomes lower following chronic uncontrollable aversion exposure. Therefore, BMA activity could be a neural marker of adaptive and maladaptive states consequent to specific and general uncontrollability, respectively.
Assuntos
Desamparo Aprendido , Estresse Psicológico , Afeto , Tonsila do Cerebelo , Animais , Eletrochoque , Masculino , CamundongosRESUMO
Whilst reward pathologies are major and common in stress-related neuropsychiatric disorders, their neurobiology and treatment are poorly understood. Imaging studies in human reward pathology indicate attenuated BOLD activity in nucleus accumbens (NAc) coincident with reward anticipation but not reinforcement; potentially, this is dopamine (DA) related. In mice, chronic social stress (CSS) leads to reduced reward learning and motivation. Here, DA-sensor fibre photometry is used to investigate whether these behavioural deficits co-occur with altered NAc DA activity during reward anticipation and/or reinforcement. In CSS mice relative to controls: (1) Reduced discriminative learning of the sequence, tone-on + appetitive behaviour = tone-on + sucrose reinforcement, co-occurs with attenuated NAc DA activity throughout tone-on and sucrose reinforcement. (2) Reduced motivation during the sequence, operant behaviour = tone-on + sucrose delivery + sucrose reinforcement, co-occurs with attenuated NAc DA activity at tone-on and typical activity at sucrose reinforcement. (3) Reduced motivation during the sequence, operant behaviour = appetitive behaviour + sociosexual reinforcement, co-occurs with typical NAc DA activity at female reinforcement. Therefore, in CSS mice, low NAc DA activity co-occurs with low reward anticipation and could account for deficits in learning and motivation, with important implications for understanding human reward pathology.
Assuntos
Dopamina , Núcleo Accumbens , Recompensa , Estresse Psicológico , Núcleo Accumbens/metabolismo , Animais , Dopamina/metabolismo , Camundongos , Masculino , Estresse Psicológico/metabolismo , Feminino , Camundongos Endogâmicos C57BL , Motivação , Antecipação Psicológica , Comportamento Animal , Reforço PsicológicoRESUMO
Reduced reward interest/learning and reward-to-effort valuation are distinct, common symptoms in neuropsychiatric disorders for which chronic stress is a major aetiological factor. Glutamate neurons in basal amygdala (BA) project to various regions including nucleus accumbens (NAc). The BA-NAc neural pathway is activated by reward and aversion, with many neurons being monovalent. In adult male mice, chronic social stress (CSS) leads to reduced discriminative reward learning (DRL) associated with decreased BA-NAc activity, and to reduced reward-to-effort valuation (REV) associated, in contrast, with increased BA-NAc activity. Chronic tetanus toxin BA-NAc inhibition replicates the CSS-DRL effect and causes a mild REV reduction, whilst chronic DREADDs BA-NAc activation replicates the CSS effect on REV without affecting DRL. This study provides evidence that stress disruption of reward processing involves the BA-NAc neural pathway; the bi-directional effects implicate opposite activity changes in reward (learning) neurons and aversion (effort) neurons in the BA-NAc pathway following chronic stress.