Archival ReportPresynaptic Leptin Action Suppresses Excitatory Synaptic Transmission onto Ventral Tegmental Area Dopamine Neurons
Section snippets
Animals
All protocols were in accordance with the ethical guidelines established by the Canadian Council for Animal care and were approved by the University of British Columbia Animal Care Committee. Male C57BL/6 mice (p21–25; University of British Columbia) were housed in groups of 3 to 5. For some experiments, mice expressing pituitary homeobox 3 tagged with green fluorescent protein (Pitx3-GFP) knock-in mice (p21–25; bred inhouse) were used to easily identify VTA dopaminergic neurons because Pitx3
Leptin Suppresses Excitatory Synaptic Transmission onto VTA Dopamine Neurons
AMPAR EPSCs were recorded from VTA dopamine neurons of mouse midbrain slices voltage-clamped at –70 mV. Bath application of leptin for 15 min caused a long-lasting depression of AMPAR EPSCs (Figure 1A,B; baseline: 98%±1% vs. leptin: 77%±6%; n = 7, p<.05). Leptin depressed AMPAR EPSCs in all four neurons that were post hoc labeled for TH. To measure NMDAR EPSCs, neurons were voltage clamped at +40 mV and measurements were taken 20 ms after the stimulus artifact, a time point at which the
Discussion
The data presented here establish a novel mechanism for leptin action in the mesolimbic incentive motivation/reward system. Leptin reduced both NMDAR- and AMPAR-mediated synaptic transmission onto dopamine neurons by reducing glutamate release from presynaptic terminals. This effect was mediated by presynaptic Jak2 and PI3K signaling, suggesting that leptin is not directly activating dopamine neurons to induce synaptic inhibition. A model of leptin inhibition of excitatory synaptic transmission
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