Paired stimulation between CA3 and CA1 alters excitability of CA3 in the rat hippocampus

Abstract It is generally accepted that the extent of plasticity is localized to the region around synapses and post-synaptic intracellular signaling cascades. We investigated the presence of long-range retrograde plasticity associated with excitability at pre-synaptic neurons (CA3) and regulated by the firing of post-synaptic neurons (CA1). We used acute hippocampus slices from transgenic rats expressing channelrhodopsin-2 (ChR2) in both CA1 and CA3 neurons. We employed a parallel photostimulation technique, which enabled robust and independent evocation of action potentials in either CA3 or CA1 neurons. Optically evoked CA3 firings were paired either with CA1 simultaneous firings or with CA1 suppression after the prolonged stimulation. Pre-synaptic excitability was monitored by measuring the optically-evoked firing rate (Opt-FR). We found that the Opt-FR of CA3 neurons was long-term up-regulated as a result of synchronous pre- and post-synaptic pairing stimulation, but down-regulated by the pre-synaptic stimulation during post-synaptic suppression. Both pairing-dependent up-regulation and down-regulation were retarded by NMDA receptor blocking or colchicine preincubation. This finding suggest that CA3 excitability is regulated by CA1 neuron activity at the time of CA3 firing.