Embryonic and postnatal development of mouse olfactory tubercle

Eduardo Martin-Lopez; Christine Xu; Teresa Liberia; Sarah J Meller; Charles A Greer

doi:10.1016/j.mcn.2019.06.002

Embryonic and postnatal development of mouse olfactory tubercle

Mol Cell Neurosci. 2019 Jul:98:82-96. doi: 10.1016/j.mcn.2019.06.002. Epub 2019 Jun 11.

Authors

Eduardo Martin-Lopez¹, Christine Xu², Teresa Liberia¹, Sarah J Meller³, Charles A Greer⁴

Affiliations

¹ Department of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
² Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
³ Department of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; The Interdepartmental Neuroscience Graduate Program, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
⁴ Department of Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA; The Interdepartmental Neuroscience Graduate Program, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. Electronic address: charles.greer@yale.edu.

PMID: 31200100
DOI: 10.1016/j.mcn.2019.06.002

Abstract

The olfactory tubercle (OT) is located in the ventral-medial region of the brain where it receives primary input from olfactory bulb (OB) projection neurons and processes olfactory behaviors related to motivation, hedonics of smell and sexual encounters. The OT is part of the dopamine reward system that shares characteristics with the striatum. Together with the nucleus accumbens, the OT has been referred to as the "ventral striatum". However, despite its functional importance little is known about the embryonic development of the OT and the phenotypic properties of the OT cells. Here, using thymidine analogs, we establish that mouse OT neurogenesis occurs predominantly between E11-E15 in a lateral-to-medial gradient. Then, using a piggyBac multicolor technique we characterized the migratory route of OT neuroblasts from their embryonic point of origin. Following neurogenesis in the ventral lateral ganglionic eminence (vLGE), neuroblasts destined for the OT followed a dorsal-ventral pathway we named "ventral migratory course" (VMC). Upon reaching the nascent OT, neurons established a prototypical laminar distribution that was determined, in part, by the progenitor cell of origin. A phenotypic analysis of OT neuroblasts using a single-color piggyBac technique, showed that OT shared the molecular specification of striatal neurons. In addition to primary afferent input from the OB, the OT also receives a robust dopaminergic input from ventral tegmentum (Ikemoto, 2007). We used tyrosine hydroxylase (TH) expression as a proxy for dopaminergic innervation and showed that TH onset occurs at E13 and progressively increased until postnatal stages following an 'inside-out' pattern. Postnatally, we established the myelination in the OT occurring between P7 and P14, as shown with CNPase staining, and we characterized the cellular phenotypes populating the OT by immunohistochemistry. Collectively, this work provides the first detailed analysis of the developmental and maturation processes occurring in mouse OT, and demonstrates the striatal nature of the OT as part of the ventral striatum (vST).

Keywords: Development; Dopaminergic innervation; Myelination; Neurogenesis; Olfactory tubercle; Striatum.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Dopaminergic Neurons / cytology
Dopaminergic Neurons / metabolism
Female
Male
Mice
Myelin Sheath / metabolism
Neurogenesis*
Olfactory Tubercle / cytology
Olfactory Tubercle / embryology*
Olfactory Tubercle / growth & development