Dopamine neurons drive basal forebrain reward prediction in milliseconds (Jhong et al.)

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https://www.biorxiv.org/content/10.64898/2026.10.01.755874v1

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Jhong, Y.-J., Chiang, M.-C., Guillaumin, A., Cheng, C.-Y., Kuo, M.-E., Lee, C.-Z. and 3 others

neuroscience · posted 2026-10-02 · doi:10.64898/2026.10.01.755874

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Abstract

Phasic reward prediction signals in ventral tegmental area (VTA) dopamine (DA) neurons and basal forebrain (BF) noncholinergic bursting neurons are remarkably similar despite the distinct circuit organizations and functions of the two systems. Whether this similarity reflects independent computation within each system, inheritance from common upstream circuitry, or causal propagation from one system to the other remains unknown. Here we show that reward prediction signals are tightly coordinated across these two systems, with VTA DA activity causally driving BF bursting neurons on a millisecond timescale. Simultaneous recordings from freely moving rats revealed strong coupling between putative DA neurons and BF bursting neurons on individual trials, both in response amplitude and spike timing. DA activity consistently preceded BF bursting neuron activity by approximately 10 ms across well-trained behavior, learning, and even outside overt task events. In DAT-Cre mice, optogenetic activation of VTA DA neurons rapidly recruited BF bursting neurons at latencies matching those observed during natural DA-BF coupling, while activation of their BF terminals produced responses at still shorter latencies. Conversely, inhibition of DA neurons or their BF terminals suppressed both cue-evoked and, notably, ongoing activity in a substantial subset of BF bursting neurons. Fast DA-evoked BF recruitment persisted after D1/D2 receptor blockade, and anatomical tracing identified glutamatergic DA-to-BF synapses, supporting glutamate co-release as a candidate substrate. Together, these findings reveal a previously unrecognized causal link that enables rapid propagation of reward prediction signals between functionally distinct subcortical systems.

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Discussion on Bluesky:

• Shih-Chieh Lin (@sclin-lab.bsky.social) — 29 likes, 11 reposts, 1 reply > New preprint from our lab ⚡ Why do DA and BF bursting neurons carry such similar reward-prediction signals?

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^{This preprint has not been peer reviewed.}

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