Olfactory Inputs to Hypothalamic Neurons Controlling Reproduction and Fertility

Cell. 2005 Nov 18;123(4):669-82. doi: 10.1016/j.cell.2005.08.039.

Abstract

In order to gain insight into sensory processing modulating reproductive behavioral and endocrine changes, we have aimed at identifying afferent pathways to neurons synthesizing luteinizing hormone-releasing hormone (LHRH, also known as gonadotropin-releasing hormone [GnRH]), a key neurohormone of reproduction. Injection of conditional pseudorabies virus into the brain of an LHRH::CRE mouse line led to the identification of neuronal networks connected to LHRH neurons. Remarkably, and in contrast to established notions on the nature of LHRH neuronal inputs, our data identify major olfactory projection pathways originating from a discrete population of olfactory sensory neurons but fail to document any synaptic connectivity with the vomeronasal system. Accordingly, chemosensory modulation of LHRH neuronal activity and mating behavior are dramatically impaired in absence of olfactory function, while they appear unaffected in mouse mutants lacking vomeronasal signaling. Further visualization of afferents to LHRH neurons across the brain offers a unique opportunity to uncover complex polysynaptic circuits modulating reproduction and fertility.

Publication types

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

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / physiology
  • Brain / virology
  • Cyclic Nucleotide-Gated Cation Channels
  • Female
  • Fertility / physiology*
  • Gonadotropin-Releasing Hormone / genetics
  • Gonadotropin-Releasing Hormone / metabolism
  • Gonadotropin-Releasing Hormone / physiology
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Herpesvirus 1, Suid / genetics
  • Hypothalamus / cytology
  • Hypothalamus / physiology*
  • Hypothalamus / virology
  • Integrases / genetics
  • Integrases / metabolism
  • Ion Channels / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinases / metabolism
  • Neural Pathways / cytology
  • Neural Pathways / physiology
  • Neural Pathways / virology
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / virology
  • Nitriles / pharmacology
  • Olfactory Bulb / cytology
  • Olfactory Bulb / physiology
  • Olfactory Bulb / virology
  • Olfactory Mucosa / drug effects
  • Olfactory Mucosa / innervation
  • Olfactory Mucosa / physiology
  • Olfactory Pathways / cytology
  • Olfactory Pathways / physiology*
  • Olfactory Pathways / virology
  • Phosphorylation
  • Preoptic Area / physiology
  • Preoptic Area / virology
  • Reproduction / physiology*
  • Septum of Brain / physiology
  • Septum of Brain / virology
  • Sex Attractants / pharmacology
  • Sexual Behavior, Animal / drug effects
  • Sexual Behavior, Animal / physiology
  • TRPC Cation Channels / genetics
  • Thymidine Kinase / genetics
  • Vomeronasal Organ / innervation
  • Vomeronasal Organ / physiology
  • tau Proteins / genetics

Substances

  • Cyclic Nucleotide-Gated Cation Channels
  • Ion Channels
  • Nitriles
  • Sex Attractants
  • TRPC Cation Channels
  • Trpc2 protein, mouse
  • tau Proteins
  • Green Fluorescent Proteins
  • Gonadotropin-Releasing Hormone
  • Thymidine Kinase
  • Mitogen-Activated Protein Kinases
  • Cre recombinase
  • Integrases
  • dichlobanil