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NEUROSCIENCE |
1 Department of Applied Science, McGlothlin-Street Hall, Room 303, The College of William and Mary, Williamsburg, VA 23187-8795, USA
2 Systems Neurobiology Laboratory, Department of Neurobiology, David Geffen School of Medicine at the University of California Los Angeles, Box 951763, Los Angeles, CA 90095-1763, USA
Inspiratory neurons of the preBötzinger complex (preBötC) form local excitatory networks and display 10–30 mV transient depolarizations, dubbed inspiratory drive potentials, with superimposed spiking. AMPA receptors are critical for rhythmogenesis under normal conditions in vitro but whether other postsynaptic mechanisms contribute to drive potential generation remains unknown. We examined synaptic and intrinsic membrane properties that generate inspiratory drive potentials in preBötC neurons using neonatal mouse medullary slice preparations that generate respiratory rhythm. We found that NMDA receptors, group I metabotropic glutamate receptors (mGluRs), but not group II mGluRs, contributed to inspiratory drive potentials. Subtype 1 of the group I mGluR family (mGluR1) probably regulates a K+ channel, whereas mGluR5 operates via an inositol 1,4,5-trisphosphate (IP3) receptor-dependent mechanism to augment drive potential generation. We tested for and verified the presence of a Ca2+-activated non-specific cation current (ICAN) in preBötC neurons. We also found that high concentrations of intracellular BAPTA, a high-affinity Ca2+ chelator, and the ICAN antagonist flufenamic acid (FFA) decreased the magnitude of drive potentials. We conclude that ICAN underlies robust inspiratory drive potentials in preBötC neurons, and is only fully evoked by ionotropic and metabotropic glutamatergic synaptic inputs, i.e. by network activity.
(Received 29 March 2007;
accepted after revision 17 April 2007;
first published online 19 April 2007)
Corresponding author C. A. Del Negro: Department of Applied Science, McGlothlin-Street Hall, Room 303, The College of William and Mary, Williamsburg, VA 23187-8795, USA. Email: cadeln{at}wm.edu
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