The nitric oxide-guanylyl cyclase signaling pathway modulates membrane activity States and electrophysiological properties of striatal medium spiny neurons recorded in vivo

J Neurosci. 2004 Feb 25;24(8):1924-35. doi: 10.1523/JNEUROSCI.4470-03.2004.


Nitric oxide (NO)-releasing interneurons are believed to regulate the activity of striatal medium spiny neurons (MSNs) that contain the NO effector enzyme guanylyl cyclase (GC). The involvement of NO-GC signaling in modulating steady-state membrane activity of striatal MSNs was examined using in vivo intracellular recordings in rats. Intrastriatal infusion of a neuronal NO synthase inhibitor or a NO scavenger via reverse microdialysis consistently decreased the amplitude of spontaneously occurring depolarized plateau potentials (up events). Intrastriatal infusion of a NO scavenger also decreased the amplitude of EPSPs evoked during electrical stimulation of the orbital prefrontal cortex. The effect of the NO scavenger on spontaneous up events was partially reversed by coperfusion with a cell-permeable cGMP analog. Intracellular injection of MSNs with a soluble GC inhibitor resulted in large decreases in the following: (1) spontaneous up-event amplitude, (2) responsiveness to depolarizing current, (3) action potential amplitude, and (4) input resistance. These effects were partially reversed by coinjection of cGMP. Conversely, intracellular injection of a phosphodiesterase inhibitor increased MSN neuron membrane excitability. These results indicate that, in the intact animal, the NO signaling pathway exerts a powerful tonic modulatory influence over the membrane activity of striatal MSNs via the activation of GC and stimulation of cGMP production.

Publication types

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

MeSH terms

  • Animals
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / physiology*
  • Cyclic GMP / analogs & derivatives*
  • Cyclic GMP / metabolism
  • Cyclic GMP / pharmacology
  • Electric Stimulation
  • Enzyme Inhibitors / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Free Radical Scavengers / pharmacology
  • Guanylate Cyclase / metabolism*
  • Male
  • Microdialysis
  • Microelectrodes
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / physiology*
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type I
  • Prefrontal Cortex / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / physiology*


  • Enzyme Inhibitors
  • Free Radical Scavengers
  • 8-bromocyclic GMP
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nos1 protein, rat
  • Guanylate Cyclase
  • Cyclic GMP