Neuroscience Letters 534 (2013) 182–187 Contents lists available at SciVerse ScienceDirect Neuroscience Letters j our nal ho me p ag e: www.elsevier.com/locate/neulet Paired stimulation between CA3 and CA1 alters excitability of CA3 in the rat hippocampus Hiroyuki Ohta a,f,∗ , Seiichiro Sakai b,f , Shin Ito b,f , Toru Ishizuka b,f , Yugo Fukazawa c , Takehito Kemuriyama a , Megumi Tandai-Hiruma a , Hajime Mushiake d,f , Yoshiaki Sato e , Hiromu Yawo b,f , Yasuhiro Nishida a a Department of Physiology, National Defense Medical College, Tokorozawa, Japan b Tohoku University Graduate School of Life Sciences, Sendai, Japan c Nagoya University Graduate School of Medicine, Nagoya, Japan d Tohoku University School of Medicine, Sendai, Japan e Teikyo Heisei University, Tokyo, Japan f Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo, Japan h i g h l i g h t s I To measure excitability of CA3 extracellularly, optogenetically evoked firing rate was used. I The excitability of CA3 was up-regulated by synchronous CA3 and CA1 pairing stimulation. I The excitability of CA3 was down-regulated by asynchronous CA3 and CA1 pairing stimulation. a r t i c l e i n f o Article history: Received 8 September 2012 Received in revised form 2 November 2012 Accepted 26 November 2012 Keywords: Hippocampus Retrograde plasticity Channelrhodopsin Optogenetics a b s t r a c t 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. © 2012 Elsevier Ireland Ltd. All rights reserved. 1. Introduction It is generally accepted that synaptic plasticity occurs in a small localized region that includes pre- and post-synaptic components. However, there is growing evidence suggesting that the somatic or axonal excitability of the presynaptic neurons can be modified by pairing the firings between presynaptic and postsynaptic neurons. For example, Poo et al. have shown that the excitability or sensi- tivity of a presynaptic neuron in a cultured network was modified ∗ Corresponding author. Tel.: +81 42 995 1489; fax: +81 42 995 1489. E-mail address: ohta@ndmc.ac.jp (H. Ohta). by spike timing between pre- and post-synaptic neurons [5,7,20]. This suggests that the plastic changes are not limited to the synap- tic region, but can extend to the pre-synaptic axon and soma. If this kind of retrograde plasticity is also present in the hippocampal network, it should contribute to forming facilitated circuits [6]. We investigated whether we could evoke retrograde plasticity in the preserved CA3-CA1 network in acute slices of the rat hippocampus. To detect the changes of a presynaptic neuron, its excitability has to be recorded independently from the correlated stimulation of its postsynaptic neurons. In cultured networks, this can be achieved by the use of a double patch-clamp technique [5,7,20]. However, the distance between a CA3 neuron and a CA1 neuron in the slice makes this technique difficult to apply. Single cellular current 0304-3940/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.neulet.2012.11.058