RESUMEN
The lateral hypothalamic (LH) projection to the ventral tegmental area (VTA) has been linked to reward processing, but the computations within the LH-VTA loop that give rise to specific aspects of behavior have been difficult to isolate. We show that LH-VTA neurons encode the learned action of seeking a reward, independent of reward availability. In contrast, LH neurons downstream of VTA encode reward-predictive cues and unexpected reward omission. We show that inhibiting the LH-VTA pathway reduces "compulsive" sucrose seeking but not food consumption in hungry mice. We reveal that the LH sends excitatory and inhibitory input onto VTA dopamine (DA) and GABA neurons, and that the GABAergic projection drives feeding-related behavior. Our study overlays information about the type, function, and connectivity of LH neurons and identifies a neural circuit that selectively controls compulsive sugar consumption, without preventing feeding necessary for survival, providing a potential target for therapeutic interventions for compulsive-overeating disorder.
Asunto(s)
Conducta Animal , Área Hipotalámica Lateral/fisiología , Área Tegmental Ventral/fisiología , Animales , Retroalimentación , Área Hipotalámica Lateral/citología , Ratones , Modelos Neurológicos , Vías Nerviosas , Neuronas/citología , Recompensa , Sacarosa , Ácido gamma-Aminobutírico/metabolismoRESUMEN
Orchestrating appropriate behavioral responses in the face of competing signals that predict either rewards or threats in the environment is crucial for survival. The basolateral nucleus of the amygdala (BLA) and prelimbic (PL) medial prefrontal cortex have been implicated in reward-seeking and fear-related responses, but how information flows between these reciprocally connected structures to coordinate behavior is unknown. We recorded neuronal activity from the BLA and PL while rats performed a task wherein competing shock- and sucrose-predictive cues were simultaneously presented. The correlated firing primarily displayed a BLAâPL directionality during the shock-associated cue. Furthermore, BLA neurons optogenetically identified as projecting to PL more accurately predicted behavioral responses during competition than unidentified BLA neurons. Finally photostimulation of the BLAâPL projection increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. Therefore, the BLAâPL circuit is critical in governing the selection of behavioral responses in the face of competing signals.
Asunto(s)
Amígdala del Cerebelo/fisiología , Corteza Prefrontal/fisiología , Castigo , Recompensa , 2-Amino-5-fosfonovalerato/administración & dosificación , 2-Amino-5-fosfonovalerato/farmacología , Potenciales de Acción/fisiología , Animales , Condicionamiento Clásico/efectos de los fármacos , Condicionamiento Clásico/fisiología , Señales (Psicología) , Discriminación en Psicología/efectos de los fármacos , Discriminación en Psicología/fisiología , Estimulación Eléctrica , Pérdida de Tono Postural/fisiología , Masculino , Microinyecciones , Inhibición Neural/fisiología , Vías Nerviosas/fisiología , Corteza Prefrontal/efectos de los fármacos , Quinoxalinas/administración & dosificación , Quinoxalinas/farmacología , Ratas , Ratas Transgénicas , SacarosaRESUMEN
Projections from the lateral hypothalamus (LH) to the ventral tegmental area (VTA), containing both GABAergic and glutamatergic components, encode conditioned responses and control compulsive reward-seeking behavior. GABAergic neurons in the LH have been shown to mediate appetitive and feeding-related behaviors. Here we show that the GABAergic component of the LH-VTA pathway supports positive reinforcement and place preference, while the glutamatergic component mediates place avoidance. In addition, our results indicate that photoactivation of these projections modulates other behaviors, such as social interaction and perseverant investigation of a novel object. We provide evidence that photostimulation of the GABAergic LH-VTA component, but not the glutamatergic component, increases dopamine (DA) release in the nucleus accumbens (NAc) via inhibition of local VTA GABAergic neurons. Our study clarifies how GABAergic LH inputs to the VTA can contribute to generalized behavioral activation across multiple contexts, consistent with a role in increasing motivational salience. VIDEO ABSTRACT.