Abstract
Affective disorders are associated with increased sensitivity to negative feedback that influences approach–avoidance decision making. Although neuroimaging studies of these disorders reveal dysregulation in primate cingulate areas 25 and 32 and the anterior hippocampus (aHipp), the causal involvement of these structures and their interaction in the primate brain is unknown. We therefore investigated the effects of localized pharmacological manipulations of areas 25 and 32 and/or the aHipp of the marmoset monkey on performance of an anxiolytic-sensitive instrumental decision-making task in which an approach–avoidance conflict is created by pairing a response with reward and punishment. During control infusions animals avoided punishment, but this bias was reduced by increasing glutamate release within the aHipp or area 32, and inactivation or 5-HT1a antagonism within area 25. Conversely, increasing glutamate release in area 25 enhanced punishment avoidance but, in contrast to previous reports, area 32 and aHipp inactivations had no effect. Simultaneous inactivation or 5-HT1a antagonism within area 25, but not area 32, abolished the reduced punishment avoidance seen after increasing aHipp glutamate. Besides providing causal evidence that these primate areas differentially regulate negative feedback sensitivity, this study links the decision-making deficits in affective disorders to aberrant aHipp–area 25 circuit activity.
Highlights
Depression and anxiety are affective disorders that change emotions and decision making to profoundly affect quality of life
While the anterior hippocampus (aHipp) is independently implicated in both approach–avoidance decision making and the symptoms and treatment of depression and anxiety (Tsetsenis et al 2007; Aupperle and Paulus 2010; Godsil et al 2013; O’Neil et al 2015), mounting correlative evidence suggests that interactions between the aHipp and medial PFC (mPFC) are crucial for negative emotion regulation
As human studies indicate that both overactivation (Hamilton et al 2011) and sclerosis (Bach et al 2014) of the aHipp, and altered 5-HT1a-mediated transmission are associated with decision-making abnormalities, we used anatomically specific intracerebral infusions of drugs designed to cause neuronal inactivation (GABA agonists that inactivate cell bodies), activation, or 5-HT1a antagonism to investigate their contribution to decision making
Summary
Depression and anxiety are affective disorders that change emotions and decision making to profoundly affect quality of life. Given that decision making deficits are core symptoms in anxiety and depression, understanding how aHipp connectivity with mPFC areas 25 and 32 contributes to approach–avoidance behavior in primates is crucial to both understanding, and alleviating the burden of these debilitating and costly disorders To address these questions, we determined the effects of temporarily manipulating the aHipp and the aHipp–mPFC circuitry of the marmoset monkey (by simultaneously manipulating areas 25 or 32 and the aHipp) on an anxiolytic-sensitive approach–avoidance behavioral paradigm developed for non-human primates (Clarke et al 2015) (Fig. 1). Given the importance of areas 25 and 32 for the regulation of emotion, we determined the effects of manipulating areas 25 and 32 independently
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