Interneurons produced in adulthood are required for the normal functioning of the olfactory bulb network and for the execution of selected olfactory behaviors

J Neurosci. 2009 Dec 2;29(48):15245-57. doi: 10.1523/JNEUROSCI.3606-09.2009.

Abstract

Olfactory bulb (OB) interneurons are continuously renewed throughout an animal's lifespan. Despite extensive investigation of this phenomenon, little is known about bulbar circuitry functioning and olfactory performances under conditions of ablated arrival of new neurons into the adult OB. To address this issue we performed morphological, electrophysiological, and behavioral analysis in mice with suppressed bulbar neurogenesis. Infusion of the antimitotic drug AraC to the lateral ventricle via 28 d osmotic minipumps abolished the arrival of newly born neurons into the adult OB without affecting the total number of granule cells. The number, dendritic arborization, and spine density of interneurons generated in adulthood, before pump installation, were also not affected by AraC treatment. As a result of ablated neurogenesis, mitral cells--the principal output neurons in the OB--receive fewer inhibitory synapses, display reduced frequency of spontaneous IPSCs, experience smaller dendrodendritic inhibition, and exhibit decreased synchronized activity. Consequently, short-term olfactory memory was drastically reduced in AraC-treated mice. In contrast, olfactory performances of AraC-treated animals were undistinguishable from those of control mice in other odor-associated tests, such as spontaneous odor discrimination and long-term odor-associative memory tasks. Altogether, our data highlight the importance of adult neurogenesis for the proper functioning of the OB network and imply that new bulbar interneurons are involved in some, but not all, odor-associated tasks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ablation Techniques / methods
  • Animals
  • Association Learning / drug effects
  • Association Learning / physiology
  • Biophysics
  • Bromodeoxyuridine / metabolism
  • Cytarabine / pharmacology
  • Discrimination, Psychological / drug effects
  • Discrimination, Psychological / physiology*
  • Electric Stimulation / methods
  • Evoked Potentials / drug effects
  • Exploratory Behavior / drug effects
  • Green Fluorescent Proteins / genetics
  • Hindlimb Suspension / methods
  • Immunosuppressive Agents / pharmacology
  • Inhibitory Postsynaptic Potentials / drug effects
  • Interneurons / drug effects
  • Interneurons / physiology*
  • Locomotion / drug effects
  • Locomotion / physiology
  • Lysine / analogs & derivatives
  • Lysine / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Net / drug effects
  • Nerve Net / physiology*
  • Neurogenesis / drug effects
  • Odorants
  • Olfactory Bulb / cytology*
  • Olfactory Perception / physiology*
  • Patch-Clamp Techniques
  • Phosphopyruvate Hydratase / metabolism
  • Potassium Channel Blockers / pharmacology
  • Recognition, Psychology / drug effects
  • Sensory Thresholds / drug effects
  • Sensory Thresholds / physiology
  • Smell / physiology*
  • Time Factors
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Immunosuppressive Agents
  • Potassium Channel Blockers
  • Cytarabine
  • Green Fluorescent Proteins
  • gamma-Aminobutyric Acid
  • Phosphopyruvate Hydratase
  • Bromodeoxyuridine
  • biocytin
  • Lysine