Dopamine D4 Receptor Excitation of Lateral Habenula Neurons via Multiple Cellular Mechanisms

摘要: Glutamatergic lateral habenula (LHb) output communicates negative motivational valence to ventral tegmental area (VTA) dopamine (DA) neurons via activation of the rostromedial nucleus (RMTg). However, LHb also receives a poorly understood DA input from VTA, which we hypothesized constitutes an important feedback loop regulating responses stimuli. Using whole-cell electrophysiology in rat brain slices, find that initiates depolarizing inward current (IDAi) and increases spontaneous firing 32% neurons. IDAi was observed upon application amphetamine or uptake blockers cocaine GBR12935, indicating involvement endogenous DA. blocked by D4 receptor (D4R) antagonists (L745,870 L741,742), mimicked selective D4R agonist (A412997). associated with increased conductance Cs+ blocker hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channel, ZD7288. shift half-activation voltage for cation (Ih) mediated HCN channels. Recordings containing fluorescent retrograde tracers revealed only cells projecting RMTg not VTA. In parallel direct depolarization, strongly synaptic glutamate release reduced GABA onto cells. These results demonstrate can excite glutamatergic multiple cellular mechanisms. Since inhibits midbrain neurons, represents may dampen neuron following activation.