Neurotensin Release from Dopamine Neurons Drives Long-Term Depression of Substantia Nigra Dopamine Signaling.

Autor: Tschumi, Christopher W., Blankenship, Harris E., Sharma, Ramaswamy, Lynch, William B., Beckstead, Michael J.
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Zdroj: Journal of Neuroscience; 8/10/2022, Vol. 42 Issue 32, p6186-6194, 9p
Abstrakt: Midbrain dopamine neurons play central physiological roles in voluntary movement, reward learning, and motivated behavior. Inhibitory signaling at somatodendritic dopamine D2 receptor (D2R) synapses modulates excitability of dopamine neurons. The neuropeptide neurotensin is expressed by many inputs to the midbrain and induces LTD of D2R synaptic currents (LTDDA); however, the source of neurotensin that is responsible for LTDDA is not known. Here we show, in brain slices from male and female mice, that LTDDA is driven by neurotensin released by dopamine neurons themselves. Optogenetic stimulation of dopamine neurons was sufficient to induce LTDDA in the substantia nigra, but not the VTA, and was dependent on neurotensin receptor signaling, postsynaptic calcium, and vacuolar-type H+-ATPase activity in the postsynaptic cell. These findings reveal a novel form of signaling between dopamine neurons involving release of the peptide neurotensin, which may act as a feedforward mechanism to increase dopamine neuron excitability. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index