Glucokinase neurons of the paraventricular nucleus of the thalamus sense glucose and decrease food consumption

The paraventricular nucleus of the thalamus (PVT) controls goal-oriented behavior through its connections to the nucleus accumbens (NAc). We previously characterized Glut2^aPVT neurons that are activated by hypoglycemia, and which increase sucrose seeking behavior through their glutamatergic projections to the NAc. Here, we identified glucokinase (Gck)-expressing neurons of the PVT (Gck^aPVT) and generated a mouse line expressing the Cre recombinase from the glucokinase locus (Gck ^Cre/+ mice). Ex vivo calcium imaging and whole-cell patch clamp recordings revealed that Gck^aPVT neurons that project to the NAc were mostly activated by hyperglycemia. Their chemogenetic inhibition or optogenetic stimulation, respectively, enhanced food intake or decreased sucrose-seeking behavior. Collectively, our results describe a neuronal population of Gck-expressing neurons in the PVT, which has opposite glucose sensing properties and control over feeding behavior than the previously characterized Glut2^aPVT neurons. This study allows a better understanding of the complex regulation of feeding behavior by the PVT.