Synaptic function and plasticity in identified inhibitory inputs onto VTA dopamine neurons

• Published in: The European journal of neuroscience Vol. 47; no. 10; pp. 1208 - 1218
• Main Authors: Polter, Abigail M., Barcomb, Kelsey, Tsuda, Ayumi C., Kauer, Julie A.
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01.05.2018
• Subjects: Animals; Dopamine; Dopamine receptors; Dopaminergic Neurons - metabolism; Dopaminergic Neurons - physiology; Drug abuse; Drug addiction; Electrical stimuli; Excitability; GABAergic circuits; GABAergic Neurons - metabolism; GABAergic Neurons - physiology; gamma-Aminobutyric Acid - metabolism; Genetics; Glycine; Glycine - metabolism; Information processing; Interneurons; Interneurons - metabolism; Interneurons - physiology; Long-Term Potentiation - physiology; LTP; Mice; Nerve endings; Neural Inhibition - physiology; Neuronal Plasticity - physiology; Neurons; Nitric oxide; Optics; Optogenetics; Reinforcement; RMTg; Rostromedial tegmental nucleus; Short-term depression; Strychnine; Synapses - metabolism; Synapses - physiology; Synaptic depression; Synaptic plasticity; Ventral Tegmental Area - metabolism; Ventral Tegmental Area - physiology; Ventral tegmentum; γ-Aminobutyric acid; RMTg; LTP; GABAergic circuits; optogenetics
• ISSN: 0953-816X; 1460-9568; 1460-9568
• DOI: 10.1111/ejn.13879

Ventral tegmental area (VTA) dopaminergic neurons are key components of the reward pathway, and their activity is powerfully controlled by a diverse array of inhibitory GABAergic inputs. Two major sources of GABAergic nerve terminals within the VTA are local VTA interneurons and neurons in the rostromedial tegmental nucleus (RMTg). Here, using optogenetics, we compared synaptic properties of GABAergic synapses on VTA dopamine neurons using selective activation of afferents that originate from these two cell populations. We found little evidence of co‐release of glutamate from either input, but RMTg‐originating synaptic currents were reduced by strychnine, suggesting co‐release of glycine and GABA. VTA‐originating synapses displayed a lower initial release probability, and at higher frequency stimulation, short‐term depression was more marked in VTA‐ but not RMTg‐originating synapses. We previously reported that nitric oxide (NO)‐induced potentiation of GABAergic synapses on VTA dopaminergic cells is lost after exposure to drugs of abuse or acute stress; in these experiments, multiple GABAergic afferents were simultaneously activated by electrical stimulation. Here we found that optogenetically‐activated VTA‐originating synapses on presumptive dopamine neurons also exhibited NO‐induced potentiation, whereas RMTg‐originating synapses did not. Despite providing a robust inhibitory input to the VTA, RMTg GABAergic synapses are most likely not those previously shown by our work to be persistently altered by addictive drugs and stress. Our work emphasises the idea that dopamine neuron excitability is controlled by diverse inhibitory inputs expected to exert varying degrees of inhibition and to participate differently in a range of behaviours. Using optogenetic activation of GABAergic neurons from either RMTg or VTA making synapses on VTA dopamine neurons, we find that RMTg‐originating but not VTA‐originating synaptic currents are reduced by strychnine, suggesting co‐release of glycine and GABA. VTA‐originating synapses display a lower initial release probability, and at higher frequency stimulation, short‐term depression is more marked in VTA‐ vs. RMTg‐originating synapses. Optogenetically‐activated VTA‐originating synapses on dopamine neurons exhibit NO‐induced potentiation, whereas RMTg‐originating synapses do not.