The Thalamus Regulates Retinoic Acid Signaling and Development of Parvalbumin Interneurons in Postnatal Mouse Prefrontal Cortex

eNeuro. 2019 Mar 11;6(1):ENEURO.0018-19.2019. doi: 10.1523/ENEURO.0018-19.2019. eCollection 2019 Jan-Feb.

Abstract

GABAergic inhibitory neurons in the prefrontal cortex (PFC) play crucial roles in higher cognitive functions. Despite the link between aberrant development of PFC interneurons and a number of psychiatric disorders, mechanisms underlying the development of these neurons are poorly understood. Here we show that the retinoic acid (RA)-degrading enzyme CYP26B1 (cytochrome P450 family 26, subfamily B, member 1) is transiently expressed in the mouse frontal cortex during postnatal development, and that medial ganglionic eminence (MGE)-derived interneurons, particularly in parvalbumin (PV)-expressing neurons, are the main cell type that has active RA signaling during this period. We found that frontal cortex-specific Cyp26b1 knock-out mice had an increased density of PV-expressing, but not somatostatin-expressing, interneurons in medial PFC, indicating a novel role of RA signaling in controlling PV neuron development. The initiation of Cyp26b1 expression in neonatal PFC coincides with the establishment of connections between the thalamus and the PFC. We found that these connections are required for the postnatal expression of Cyp26b1 in medial PFC. In addition to this region-specific role in postnatal PFC that regulates RA signaling and PV neuron development, the thalamocortical connectivity had an earlier role in controlling radial dispersion of MGE-derived interneurons throughout embryonic neocortex. In summary, our results suggest that the thalamus plays multiple, temporally separate roles in interneuron development in the PFC.

Keywords: Cyp26b1; interneurons; parvalbumin; prefrontal cortex; retinoic acid; thalamocortical.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Gene Expression Regulation, Developmental
  • Homeodomain Proteins / metabolism
  • Interneurons / metabolism*
  • Male
  • Mice, Transgenic
  • Neural Pathways / cytology
  • Neural Pathways / metabolism
  • Parvalbumins / metabolism*
  • Prefrontal Cortex / growth & development
  • Prefrontal Cortex / metabolism*
  • Retinal Dehydrogenase / metabolism
  • Retinoic Acid 4-Hydroxylase / genetics
  • Retinoic Acid 4-Hydroxylase / metabolism*
  • Thalamus / growth & development
  • Thalamus / metabolism*
  • Tretinoin / metabolism*

Substances

  • Gbx2 protein, mouse
  • Homeodomain Proteins
  • Parvalbumins
  • Tretinoin
  • Cyp26b1 protein, mouse
  • Retinoic Acid 4-Hydroxylase
  • Retinal Dehydrogenase
  • retinaldehyde dehydrogenase 3, mouse