RESUMO
Corticostriatal projection neurons from prelimbic medial prefrontal cortex to the nucleus accumbens core critically regulate drug-seeking behaviors, yet the underlying encoding dynamics whereby these neurons contribute to drug seeking remain elusive. Here we use two-photon calcium imaging to visualize the activity of corticostriatal neurons in mice from the onset of heroin use to relapse. We find that the activity of these neurons is highly heterogeneous during heroin self-administration and seeking, with at least 8 distinct neuronal ensembles that display both excitatory and inhibitory encoding dynamics. These neuronal ensembles are particularly apparent during relapse, where excitatory responses are amplified compared to heroin self-administration. Moreover, we find that optogenetic inhibition of corticostriatal projection neurons attenuates heroin seeking regardless of the relapse trigger. Our results reveal the precise corticostriatal activity dynamics underlying drug-seeking behaviors and support a key role for this circuit in mediating relapse to drug seeking.
RESUMO
Lack of behavioral suppression typifies substance use disorders, yet the neural circuit underpinnings of drug-induced behavioral disinhibition remain unclear. Here, we employ deep-brain two-photon calcium imaging in heroin self-administering mice, longitudinally tracking adaptations within a paraventricular thalamus to nucleus accumbens behavioral inhibition circuit from the onset of heroin use to reinstatement. We find that select thalamo-accumbal neuronal ensembles become profoundly hypoactive across the development of heroin seeking and use. Electrophysiological experiments further reveal persistent adaptations at thalamo-accumbal parvalbumin interneuronal synapses, whereas functional rescue of these synapses prevents multiple triggers from initiating reinstatement of heroin seeking. Finally, we find an enrichment of µ-opioid receptors in output- and cell-type-specific paraventricular thalamic neurons, which provide a mechanism for heroin-induced synaptic plasticity and behavioral disinhibition. These findings reveal key circuit adaptations that underlie behavioral disinhibition in opioid dependence and further suggest that recovery of this system would reduce relapse susceptibility.
Assuntos
Heroína , Transtornos Relacionados ao Uso de Opioides , Ratos , Camundongos , Animais , Heroína/farmacologia , Ratos Sprague-Dawley , Autoadministração/métodos , Neurônios , Núcleo Accumbens/fisiologiaRESUMO
In three studies, we examined food as an elicitor of nostalgia. Study 1 participants visualised eating either a nostalgic or regularly consumed food. Study 2 participants visualised consuming 12 foods. Study 3 participants consumed 12 flavour samples. Following their food experiences, all participants responded to questions regarding the profile of food-evoked nostalgia (i.e. autobiographical relevance, arousal, familiarity, positive and negative emotions) and several psychological functions (i.e. positive affect, self-esteem, social connectedness, meaning in life). Study 2 and 3 participants also reported their state nostalgia. Results revealed that food is a powerful elicitor of nostalgia. Food-evoked nostalgia has a similar contextual profile to previously examined elicitors, but is a predominantly positive emotional experience. Food-evoked nostalgia served multiple psychological functions and predicted greater state nostalgia.