Protracted neuronal recruitment in the temporal lobe of young children

The human brain's temporal lobe contains the entorhinal cortex (EC), a highly interconnected integrative hub for sensory and spatial information; key for episodic memory formation and the primary source of cortical hippocampal inputs. The human EC continues to develop during childhood, yet neurogenesis and neuronal migration to the EC are widely considered complete by birth. Here we show that the human temporal lobe contains many young neurons migrating into the postnatal EC and adjacent regions; with a large tangential stream persisting ~1 year and radial dispersal until ~2-3 years. In contrast, we found no equivalent postnatal migration in rhesus macaque (Macaca mulatta). Immunostaining and single-nuclei RNA-seq (snRNA-seq) of ganglionic eminence (GE) germinal zones, EC stream, and postnatal EC reveals that most EC stream migrating cells are derived from the caudal GE and become LAMP5+RELN+ inhibitory interneurons. These late-arriving interneurons could continue to shape the processing of sensory and spatial information well into postnatal life when children are actively interacting with their environment. The EC is one of the first brain regions affected in Alzheimer’s disease and recent work links the decline in cognitive function to the loss of LAMP5+RELN+ cells. Our investigation reveals that many of these cells arrive in the EC through a major postnatal migratory stream in early childhood. snRNA-seq of snap frozen samples of entorhinal cortex, ganglionic eminences, and the EC stream from 9 human donors (ranging from 23 GW to 27 years of age). In one multiplexed run, nuclei from 5 donors were pooled together and split in two samples (replicate 1 and replicate 2). A second, non-multiplexed run, consisting of samples from 4 other donors, was carried out as multiple individual samples. Processed data (count matrices -- after SoupX to attenuate ambient RNA contamination -- , filtered barcodes and genes) is provided here. Raw reads are deposited on dbGaP. **Submitter declares that the raw data will be deposited in dbGaP due to privacy concerns**