LH-Nts Neurons Regulate VTA Calcium Dynamics Via Releasing GABA and Nts

The peripheral and central nervous systems have numerous examples of two or more neuroactive products co-existing in the same neuron[1],which can simultaneously be released as both fast-acting neurotransmitters and slow-acting regulatory neuropeptides[2].For example,neurons in the lateral hypothalamus(LH)release both irritant neurotensin(Nts)and inhibitory-aminobutyric acid(GABA),two counterproductive substances[3].LH-Nts neurons project to the ventral tegmental area(VTA)and form synaptic connections with dopamine(DA)neurons to regulate reward[4-6].More critically,VTA-DA neurons express the Nts receptor Ntsrl and play a crucial role in cognition,anesthesia,reward,and disgust[4,7,8].Nevertheless,a mechanistic understanding of how stimulation and inhibition work together to control the output of neural circuits remains unclear.It is very difficult to selectively isolate these signaling pathways in cell and circuit-specific manners.