Mapping the cell-surface molecule repertoires patterning hippocampal CA1 border interneuron connectivity

The proper function of neural circuits depends on precise patterns of connectivity between excitatory and inhibitory neurons. Each neuronal cell type expresses a distinct combination of cell-surface molecules (CSMs) important for specifying its pattern of connectivity. Dissecting how cell type-specific CSM repertoires determine the connectivity pattern of each neuron remains a major challenge, especially for interneurons that provide the inhibition necessary to control the activity of excitatory neurons. Stratum radiatum and stratum lacunosum-moleculare border interneurons in area CA1 are strategically positioned to modulate hippocampal output, yet they remain one of the least understood populations of interneurons. Their heterogeneity in terms of gene expression and connectivity, and lack of genetic access, have hampered the analysis of the molecular programs controlling their functional connectivity. Recent technological advances now enable us to start disentangling this problem. Using PatchSeq to combine functional, morphological, and transcriptional profiling of the same cell together with a border interneuron-specific Cre line we have generated, we can now begin to characterize border interneuron diversity and map the CSM repertoires that specify their patterns of connectivity during development. The results will provide an essential basis for a deeper mechanistic understanding of the role of border interneurons in hippocampal circuit function.