Abstract
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.
Highlights
Spike timing-dependent plasticity (STDP) is a form of Hebbian learning that depends on the order and precise timing of presynaptic and postsynaptic spikes (Gerstner et al, 1996; Markram et al, 1997; Bi and Poo, 1998; Song et al, 2000)
Plasticity was induced in current clamp mode using an induction protocol consisting of 100 pairings of a single excitatory postsynaptic potentials (EPSPs) followed by a single postsynaptic spike or a single postsynaptic spike followed by a single EPSP at 0.2 Hz
The application of atropine prevented acetylcholine-facilitated timing-dependent long-term depression (t-LTD), resulting in significant timing-dependent long-term potentiation (t-LTP) instead (Dt =+10 ms; +ACh: 63 ± 9%, t(4) = 4.1, p=0.0146 vs. 100%, n = 5; +ACh + Atropine: 141 ± 8%, t(5) = 5.1, p=0.0037 vs. 100%, n = 6; t(9) = 6.5, p
Summary
Spike timing-dependent plasticity (STDP) is a form of Hebbian learning that depends on the order and precise timing of presynaptic and postsynaptic spikes (Gerstner et al, 1996; Markram et al, 1997; Bi and Poo, 1998; Song et al, 2000). STDP is a computationally attractive mechanism that has been implicated in several forms of learning and memory including competitive Hebbian learning (Song et al, 2000; Clopath et al, 2010). Hippocampal synaptic plasticity (Bliss and Lomo, 1973; Bliss and Collingridge, 1993), including STDP (Bi and Poo, 1998; Debanne et al, 1998; Kwag and Paulsen, 2009; Andrade-Talavera et al, 2016), is believed to mediate the encoding of spatial memories (Morris et al, 1986; Tsien et al, 1996). We wished to establish whether the temporal characteristics of cholinergic and dopaminergic modulation of hippocampal synaptic plasticity can explain key aspects of adaptive foraging behavior in a changing environment such as exploration and reward-seeking navigation, including unlearning of previously exploited reward locations
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