Differential expression of long-term depression, and synaptic tagging and capture in mouse hippocampal area CA2 synapses.

CA2 hippocampal neurons have received renewed interest due to their unique functions and plasticity properties that differ between synapses within the same neuronal population. However, detailed studies on long-term depression (LTD) in CA2 pyramidal neurons are lacking. In this study, LTD was induced and characterized at both Schaffer collateral-CA2 (SC-CA2) and entorhinal cortex-CA2 (EC-CA2) synapses in young, male mice. This LTD was found to be dependent on N-methyl-D-aspartate receptors, protein synthesis, and p75 neurotrophin receptors. However, weaker stimulations could only induce early LTD in EC-CA2 but not SC-CA2 synapses, consistent with its "plasticity-resistant" nature. CA2 LTD is capable of undergoing heterosynaptic synaptic tagging and capture (STC), although the machinery involved differs between SC-CA2 and EC-CA2 synapses. SC-CA2, but not EC-CA2, requires precursor brain-derived neurotrophic factor activity to maintain LTD. Subsequently, quantitative shotgun proteomics analysis yields complexin-2 as a strong candidate plasticity-related product involved in LTD in the CA2. These results reveal interesting differences in STC machinery between synaptic populations of a common set of neurons, enhancing our understanding of hippocampal circuitry involving the CA2. Interesting implications regarding the heterogeneous biochemical makeup of CA2 pyramidal neurons and fundamental STC theory that arise as a consequent of our results are also discussed further.