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Only recently have more specific circuit-probing techniques become available to inform previous reports implicating the rodent hippocampus in orexigenic appetitive processing1–4. This function has been reported to be mediated at least in part by lateral hypothalamic inputs, including those involving orexigenic lateral hypothalamic neuropeptides, such as melanin-concentrating hormone5,6. This circuit, however, remains elusive in humans. Here we combine tractography, intracranial electrophysiology, cortico-subcortical evoked potentials, and brain-clearing 3D histology to identify an orexigenic circuit involving the lateral hypothalamus and converging in a hippocampal subregion. We found that low-frequency power is modulated by sweet-fat food cues, and this modulation was specific to the dorsolateral hippocampus. Structural and functional analyses of this circuit in a human cohort exhibiting dysregulated eating behaviour revealed connectivity that was inversely related to body mass index. Collectively, this multimodal approach describes an orexigenic subnetwork within the human hippocampus implicated in obesity and related eating disorders.An appetite-regulating subnetwork in humans involving the lateral hypothalamus and the dorsolateral hippocampus is implicated in obesity and related eating disorders. [ABSTRACT FROM AUTHOR]

Dissecting MDMA: MDMA, commonly known as ecstasy, is a psychoactive drug primarily used for recreational purposes. Because of its prosocial effects, MDMA is currently being evaluated for the treatment of psychiatric disorders. Unfortunately, the rewarding addictive properties hinder the therapeutic use. Now, Heifets et al. investigated the mechanisms mediating the effects of MDMA in rodents and found that the prosocial and the rewarding effects are mediated by independent mechanisms. The prosocial effects are mediated by activation of the serotoninergic system, whereas the rewarding effect requires the activation of the dopaminergic signaling. The results pave the way for the development of more specific therapeutic intervention with less side effects. The extensively abused recreational drug (±)3,4-methylenedioxymethamphetamine (MDMA) has shown promise as an adjunct to psychotherapy for treatment-resistant psychiatric disease. It is unknown, however, whether the mechanisms underlying its prosocial therapeutic effects and abuse potential are distinct. We modeled both the prosocial and nonsocial drug reward of MDMA in mice and investigated the mechanism of these processes using brain region–specific pharmacology, transgenic manipulations, electrophysiology, and in vivo calcium imaging. We demonstrate in mice that MDMA acting at the serotonin transporter within the nucleus accumbens is necessary and sufficient for MDMA's prosocial effect. MDMA's acute rewarding properties, in contrast, require dopaminergic signaling. MDMA's prosocial effect requires 5-HT1b receptor activation and is mimicked by d-fenfluramine, a selective serotonin-releasing compound. By dissociating the mechanisms of MDMA's prosocial effects from its addictive properties, we provide evidence for a conserved neuronal pathway, which can be leveraged to develop novel therapeutics with limited abuse liability. [ABSTRACT FROM AUTHOR]