Most of our knowledge of hippocampal circuit function derives from rodent work. Indeed, it remains unclear whether the properties of human neural circuits differ from those of rodent circuits. In a new study, Watson et al. reveal distinct circuit features of the human hippocampal CA3 region.

To assess human CA3, the authors studied slices of hippocampal tissue from people who underwent a unilateral temporal lobe resection to treat temporal lobe epilepsy through a combination of multicellular patch-clamp-based circuit mapping and expansion-based superresolution microscopy. They obtained recordings from the tissue of 8 individuals, on the basis of which they identified 262 CA3 pyramidal neurons. Analysis of this dataset on the basis of electrophysiological and morphological criteria revealed 10 putative monosynaptic connections out of 789 tested pyramidal neuron connections, equating to a connection probability of 1.27%. The intersomatic distance between synaptically connected neurons varied considerably, which suggests that human CA3 is a sparse but broadly connected recurrent network.