Optical imaging method with voltage-sensitive dye as a tool to explore learning rules acting in synaptic strength change upon burst stimulation in area CA1 of rat hippocampal slices

In theoretical studies of learning and memory in neural networks, Hebbian rule is thought to have central importance. The present paper examine if the actual Hebbian rule is actually working in well-known physiological model. In a physiological model of hippocampal slice preparation, it is well established that the paired postsynaptic depolarization of dendrites with afferent spikes is considered a central long-term potentiation (LTP)-induction mechanism, and a prime example of a Hebb synapse. By directly visualizing neural responses with a voltage-sensitive dye (VSD) in hippocampal slices, we observed that cells lost spikes during sustained depolarization that occurred throughout standard, LTP-producing tetanic stimulation. Thus we concluded that the standard tetanic stimulation induced LTP was not obey Hebb´s rule at least in strict sense. On the other hand, natural burst stimulus, a θ-burst stimulation, which mimics actual bursting observed in vivo preparation, was found to elicit exaggerated spike firing. Thus, it can be said that θ-burst stimulation elicits Hebbian plasticity. Our results show that the burst stimulation can induce both Hebbian and non-Hebbian plasticity depending on the temporal pattern of burst stimulation. Our results also imply that this can be switched by dendritic DC-membrane potential, and the optical recording method is suitable to explore the phenomenon that directly connected to the learning rule in the actual tissue.