Developmentally structured coactivity and plasticity in the hippocampal trisynaptic loop

Research into the hippocampus has long emphasized its plasticity (McClelland et al., 1995), though recent reports have highlighted its remarkably stable firing patterns (Mizuseki et al., 2013). How plasticity updates networks maintaining their dynamics remains an open question, largely due to a lack of experimental access points into network stability. Development may provide one such access point. We previously showed that CA1 pyramidal neurons of the same embryonic birthdate exhibit prominent cofiring across different brain states and overlapping place tuning during behavior (Author et al., 2022). Prior anatomical work showed that same birthdate neurons across hippocampal subregions (DG-CA3, CA3-CA1) are synaptic partners (Deguchi et al., 2011). This suggests developmentally installed, functionally relevant circuit motifs throughout the entire hippocampal trisynaptic loop. Here, we investigate this hypothesis by monitoring activity of same birthdate excitatory neurons across all hippocampal subregions and study how it updates with learning. First, neural ensembles of the dentate gyrus (DG) and CA3 were monitored with high density silicon probes, and birthdate-defined populations expressing ChR2 were identified in vivo with short-pulse optogenetics. Same birthdate DG granule cells displayed prominent coactivity in dentate spikes, a population pattern triggered by entorhinal input. Furthermore, CA3 neurons that co-discharged upon mossy-fiber stimulation tended to cofire during spontaneous activity bursts. This suggests that same birthdate granule cells shape the activity of downstream CA3 partners, consistent with their synaptic interconnectedness (Deguchi et al., 2011). To directly explore the interactions and plasticity of same birthdate populations across synaptically connected areas, we birthdated populations of CA3 and CA1 neurons and monitored their joint activity during a hippocampus dependent learning task requiring plasticity (Dupret et al., 2010). Same birthdate CA1 and CA3 pyramidal neurons exhibited overlapping place fields, which remapped together with learning. This indicates that plasticity-dependent synaptic modifications are subject to a developmental circuit constraint.