Immature excitatory neurons develop during adolescence in the human amygdala

Shawn F Sorrells,Ricardo Insausti,Kadellyn Sandoval,Arnold R Kriegstein,Edward F Chang,Vicente Herranz-Pérez,Simone Mayer,Arturo Alvarez-Buylla,Jose Manuel Garcia-Verdugo,John L Rubenstein,Dmitry Velmeshev,Eric J Huang,Mercedes F Paredes

doi:10.1038/s41467-019-10765-1

Abstract

The human amygdala grows during childhood, and its abnormal development is linked to mood disorders. The primate amygdala contains a large population of immature neurons in the paralaminar nuclei (PL), suggesting protracted development and possibly neurogenesis. Here we studied human PL development from embryonic stages to adulthood. The PL develops next to the caudal ganglionic eminence, which generates inhibitory interneurons, yet most PL neurons express excitatory markers. In children, most PL cells are immature (DCX+PSA-NCAM+), and during adolescence many transition into mature (TBR1+VGLUT2+) neurons. Immature PL neurons persist into old age, yet local progenitor proliferation sharply decreases in infants. Using single nuclei RNA sequencing, we identify the transcriptional profile of immature excitatory neurons in the human amygdala between 4–15 years. We conclude that the human PL contains excitatory neurons that remain immature for decades, a possible substrate for persistent plasticity at the interface of the hippocampus and amygdala.

Highlights

The human amygdala grows during childhood, and its abnormal development is linked to mood disorders
A region of the primate amygdala located near the temporal lobe lateral ventricle called the paralaminar nuclei (PL), does, contain a large population of neurons expressing the microtubule-associated protein doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM), both of which are found in immature neurons
The developing PL was evident as a layer of higher-density COUP-TFII+SP8–PROX1– cells between the basolateral amygdala (BLA) and caudal ganglionic eminence (CGE), with a large medial region (MPL) and a thin lateral extension (LPL) (Fig. 1h, j–m, Supplementary Fig. 1)

Summary

Introduction

The human amygdala grows during childhood, and its abnormal development is linked to mood disorders. A region of the primate amygdala located near the temporal lobe lateral ventricle (tLV) called the paralaminar nuclei (PL), does, contain a large population of neurons expressing the microtubule-associated protein doublecortin (DCX) and polysialylated neural cell adhesion molecule (PSA-NCAM), both of which are found in immature neurons. This region contains cells with simple morphology and immature gene expression signature in several species of monkeys[3,4,5,6,7] and in humans[8,9]. The GABAergic cells in the intercalated nuclei have been lineage-traced in rodents to the dorsal lateral ganglionic eminence (LGE)[18] and express the transcription factor SP8, but the embryonic development and identity of the cells in the human PL has not been explored

Methods

Results

Conclusion