Journal
ELIFE
Volume 6, Issue -, Pages 1-18Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.27756
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Funding
- Medical Research Council
- Engineering and Physical Sciences Research Council
- Wellcome [095495, 200790/Z/16/Z]
- Biotechnology and Biological Sciences Research Council [BB/N013956/1, BB/N019008/1]
- BBSRC [BB/P019560/1, BB/N00096X/1, BB/N019008/1, BB/P018785/1] Funding Source: UKRI
- Wellcome Trust [200790/Z/16/Z] Funding Source: Wellcome Trust
- Biotechnology and Biological Sciences Research Council [BB/P018785/1, BB/N00096X/1, BB/P019560/1, BB/N019008/1] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [1527310] Funding Source: researchfish
- Medical Research Council [1233554] Funding Source: researchfish
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Spike timing-dependent plasticity (STDP) is under neuromodulatory control, which is correlated with distinct behavioral states. Previously, we reported that dopamine, a reward signal, broadens the time window for synaptic potentiation and modulates the outcome of hippocampal STDP even when applied after the plasticity induction protocol (Brzosko et al., 2015). Here, we demonstrate that sequential neuromodulation of STDP by acetylcholine and dopamine offers an efficacious model of reward-based navigation. Specifically, our experimental data in mouse hippocampal slices show that acetylcholine biases STDP toward synaptic depression, whilst subsequent application of dopamine converts this depression into potentiation. Incorporating this bidirectional neuromodulation-enabled correlational synaptic learning rule into a computational model yields effective navigation toward changing reward locations, as in natural foraging behavior. Thus, temporally sequenced neuromodulation of STDP enables associations to be made between actions and outcomes and also provides a possible mechanism for aligning the time scales of cellular and behavioral learning.
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