  Neuromodulation plays a fundamental role in the acquisition of new
behaviours. Our experimental findings show that, whereas acetylcholine biases
hippocampal synaptic plasticity towards depression, the subsequent application
of dopamine can retroactively convert depression into potentiation. We
previously demonstrated that incorporating this sequentially neuromodulated
Spike-Timing-Dependent Plasticity (STDP) rule in a network model of navigation
yields effective learning of changing reward locations. Here, we further
characterize the effects of cholinergic depression on behaviour. We find that
acetylcholine, by allowing learning from negative outcomes, influences
exploration in a non-trivial manner that highly depends on the specifics of the
model, the environment and the task. Interestingly, sequentially neuromodulated
STDP also yields flexible learning, surpassing the performance of other
reward-modulated plasticity rules.
