Presynaptic muscarinic receptors enhance glutamate release at the mitral/tufted to granule cell dendrodendritic synapse in the rat main olfactory bulb.
The mammalian olfactory bulb receives multiple modulatory inputs, including a cholinergic input from the basal forebrain. Understanding the functional roles played by the cholinergic input requires an understanding of the cellular mechanisms it modulates. In an in vitro olfactory bulb slice preparation we demonstrate cholinergic muscarinic modulation of glutamate release onto granule cells that results in gamma-aminobutyric acid (GABA) release onto mitral/tufted cells. We demonstrate that the broad-spectrum cholinergic agonist carbachol triggers glutamate release from mitral/tufted cells that activates both AMPA and NMDA receptors on granule cells. Activation of the granule cell glutamate receptors leads to calcium influx through voltage-gated calcium channels, resulting in spike-independent, asynchronous GABA release at reciprocal dendrodendritic synapses that granule cells form with mitral/tufted cells. This cholinergic modulation of glutamate release persists through much of postnatal bulbar development, suggesting a functional role for cholinergic inputs from the basal forebrain in bulbar processing of olfactory inputs and possibly in postnatal development of the olfactory bulb.
Ghatpande
Ambarish S
AS
Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA. aghatpande@monell.org
Gelperin
Alan
A
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002217:Carbachol / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008954:Models, Biological; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009830:Olfactory Bulb / Q000166:cytology*; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002217:Carbachol; D018679:Cholinergic Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018698:Glutamic Acid; D018727:Muscarinic Antagonists; D010852:Picrotoxin; D010890:Pirenzepine; D011976:Receptors, Muscarinic; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D014633:Valine; C056639:2-amino-5-phosphopentanoic acid