Androgens modulate NMDA receptor-mediated EPSCs in the zebra finch song system

J Neurophysiol. 1999 Nov;82(5):2221-34. doi: 10.1152/jn.1999.82.5.2221.


Androgens potently regulate the development of learned vocalizations of songbirds. We sought to determine whether one action of androgens is to functionally modulate the development of synaptic transmission in two brain nuclei, the lateral part of the magnocellular nucleus of the anterior neostriatum (LMAN) and the robust nucleus of the archistriatum (RA), that are critical for song learning and production. We focused on N-methyl-D-aspartate-excitatory postsynaptic currents (NMDA-EPSCs), because NMDA receptor activity in LMAN is crucial to song learning, and because the LMAN synapses onto RA neurons are almost entirely mediated by NMDA receptors. Whole cell recordings from in vitro brain slice preparations revealed that the time course of NMDA-EPSCs was developmentally regulated in RA, as had been shown previously for LMAN. Specifically, in both nuclei, NMDA-EPSCs become faster over development. We found that this developmental transition can be modulated by androgens, because testosterone treatment of young animals caused NMDA-EPSCs in LMAN and RA to become prematurely fast. These androgen-induced effects were limited to fledgling and juvenile periods and were spatially restricted, in that androgens did not accelerate developmental changes in NMDA-EPSCs recorded in a nonsong area, the Wulst. To determine whether androgens had additional effects on LMAN or RA neurons, we examined several other physiological and morphological parameters. In LMAN, testosterone affected alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprianate-EPSC (AMPA-EPSC) decay times and the ratio of peak synaptic glutamate to AMPA currents, as well as dendritic length and spine density but did not alter soma size or dendritic complexity. In contrast, testosterone did not affect any of these parameters in RA, which demonstrates that exogenous androgens can have selective actions on different song system neurons. These data are the first evidence for any effect of sex steroids on synaptic transmission within the song system. Our results support the idea that endogenous androgens limit sensitive periods for song learning by functionally altering synaptic transmission in song nuclei.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / physiology*
  • Androgens / pharmacology
  • Androgens / physiology*
  • Animals
  • Brain / drug effects
  • Brain / growth & development
  • Brain / physiology*
  • Dendrites / physiology
  • Dihydrotestosterone / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology*
  • In Vitro Techniques
  • Male
  • Neurons / drug effects
  • Neurons / physiology*
  • Quinoxalines / pharmacology*
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Songbirds / physiology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Testosterone / pharmacology
  • Vocalization, Animal / physiology*
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology


  • Androgens
  • Excitatory Amino Acid Antagonists
  • Quinoxalines
  • Receptors, N-Methyl-D-Aspartate
  • Dihydrotestosterone
  • 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
  • Testosterone
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid