Abstract
Area CA2 is emerging as an important region for hippocampal memory formation. However, how CA2 pyramidal neurons (PNs) are engaged by intrahippocampal inputs remains unclear. Excitatory transmission between CA3 and CA2 is strongly inhibited and is not plastic. We show in mice that different patterns of activity can in fact increase the excitatory drive between CA3 and CA2. We provide evidence that this effect is mediated by a long-term depression at inhibitory synapses (iLTD), as it is evoked by the same protocols and shares the same pharmacology. In addition, we show that the net excitatory drive of distal inputs is also increased after iLTD induction. The disinhibitory increase in excitatory drive is sufficient to allow CA3 inputs to evoke action potential firing in CA2 PNs. Thus, these data reveal that the output of CA2 PNs can be gated by the unique activity-dependent plasticity of inhibitory neurons in area CA2.
Highlights
After a stable baseline period, we applied either an High-frequency stimulation (HFS) protocol (100 pulses at 100 Hz repeated twice) or a 10 Hz protocol (100 pulses at 10 Hz repeated twice). These two protocols efficiently induce iLTD of inhibitory inputs in area CA2 (Piskorowski and Chevaleyre, 2013). We found that both the HFS and 10 Hz protocol evoked a lasting increase in the amplitude of the compound field PSPs (fPSPs) [with 100 Hz stimulation: 160.5 Ϯ 4.2% of fPSP amplitude, p Ͻ 0.00001, n ϭ 10 (Fig. 1A); with 10 Hz stimulation: 144.8 Ϯ 9.9% of fPSP amplitude, p ϭ 0.0034, n ϭ 8 (Fig. 1B)]
To address whether a change in the excitability of CA3 pyramidal neurons (PNs) was responsible for the increase in the fEPSP in CA2, we measured the amplitude of the fiber volley
We have shown that the net excitatory drive between CA3 and CA2 can be persistently increased in an activity-dependent manner, even though the CA3–CA2 excitatory transmission does not express a direct longterm potentiation (LTP)
Summary
Recent findings have revealed that hippocampal area CA2 plays an important role in learning and memory. It has recently been found that the receptive fields of CA2 pyramidal neurons (PNs) change rapidly with time, indicating that this region is playing a role in hippocampal. A clearer understanding of the connectivity in area CA2 has recently evolved (Chevaleyre and Siegelbaum, 2010; Cui et al, 2013; Rowland et al, 2013; Kohara et al, 2014); a better understanding of the plasticity of these connections is critical for understanding how this region contributes to hippocampal learning
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