Hebbian and non-Hebbian timing-dependent plasticity in the hippocampal CA3 region.

The timing between synaptic inputs has been proposed to play a role in the induction of plastic changes that enable neural circuits to store information. In the case of spike timing-dependent plasticity (STDP), this relates to the interval between a synaptic input and a postsynaptic spike, thus providing a conceptual link to the Hebb learning rule. Experiments have documented STDP in many synapses and brain regions, and computational models have tested its utility in many neural network functions. However, questions remain about whether timing plays a role in plasticity during natural activity, and whether it can function in information storage. The present study used imaging with voltage sensitive dye to investigate the effectiveness of input timing in the plasticity of responses in the CA3 region of hippocampal slices. Plasticity was induced by sequential dual-site stimulation at 10 ms intervals of either synaptic inputs and cell bodies (synaptic-somatic induction) or of two sets of synaptic inputs (synaptic-synaptic induction). Both protocols potentiated responses, with greater potentiation of responses to the first stimulation of the sequence than the second. Neither of these protocols induced depression. Synaptic-somatic stimulation was much more effective than synaptic-synaptic stimulation in evoking somatic action potentials, but both protocols potentiated responses equally well. This suggests that sequential dual-site stimulation can potentiate equally well with very different degrees of somatic action potential firing. With synaptic-somatic induction, potentiation was focused at the sites of stimulation. In contrast, with synaptic-synaptic induction, the distribution of potentiation varied greatly. Changes in the spatial distribution of responses indicated that sequential dual-site stimulation functions poorly in the storage of activity patterns. These results suggest that in the hippocampal CA3 region, timed sequential activation of two inputs is less effective than theta bursts, both in the induction of LTP and in the storage of information.