Diversity of dendritic morphology and entorhinal cortex synaptic effectiveness in mouse CA2 pyramidal neurons

Excitatory synaptic inputs from specific brain regions are often targeted to distinct dendritic arbors on hippocampal pyramidal neurons. Recent work has suggested that CA2 pyramidal neurons respond robustly and preferentially to excitatory input into the stratum lacunosum moleculare (SLM), with a relatively modest response to Schaffer collateral excitatory input into stratum radiatum (SR) in acute mouse hippocampal slices, but the extent to which this difference may be explained by morphology is unknown. In an effort to replicate these findings and to better understand the role of dendritic morphology in shaping responses from proximal and distal synaptic sites, we measured excitatory postsynaptic currents and action potentials in CA2 pyramidal cells in response to SR and SLM stimulation and subsequently analyzed confocal images of the filled cells. We found that, in contrast to previous reports, SR stimulation evoked substantial responses in all recorded CA2 pyramidal cells. Strikingly, however, we found that not all neurons responded to SLM stimulation, and in those neurons that did, responses evoked by SLM and SR were comparable in size and effectiveness in inducing action potentials. In a comprehensive morphometric analysis of CA2 pyramidal cell apical dendrites, we found that the neurons that were unresponsive to SLM stimulation were the same ones that lacked substantial apical dendritic arborization in the SLM. Neurons responsive to both SR and SLM stimulation had roughly equal amounts of dendritic branching in each layer. Remarkably, our study in mouse CA2 generally replicates the work characterizing the diversity of CA2 pyramidal cells in the guinea pig hippocampus. We conclude, then, that like in guinea pig, mouse CA2 pyramidal cells have a diverse apical dendrite morphology that is likely to be reflective of both the amount and source of excitatory input into CA2 from the entorhinal cortex and CA3.