Parallel regulation of a modulator-activated current via distinct dynamics underlies comodulation of motor circuit output.

Full Abstract

The cellular mechanisms underlying comodulation of neuronal networks are not elucidated in most systems. We are addressing this issue by determining the mechanism by which a peptide hormone, crustacean cardioactive peptide (CCAP), modulates the biphasic (protraction/retraction) gastric mill (chewing) rhythm driven by the projection neuron MCN1 in the crab stomatogastric ganglion. MCN1 activates this rhythm by slow peptidergic (CabTRP Ia) and fast GABAergic excitation of the reciprocally inhibitory central pattern generator neurons LG (protraction) and Int1 (retraction), respectively. MCN1 synaptic transmission is limited to the retraction phase, because LG inhibits MCN1 during protraction. Bath-applied CCAP also excites both LG and Int1, but selectively prolongs protraction. Here, we use computational modeling and dynamic-clamp manipulations to establish that CCAP prolongs the gastric mill protractor (LG) phase and maintains the retractor (Int1) phase duration by activating the same modulator-activated inward current (I(MI)) in LG as MCN1-released CabTRP Ia. However, the CCAP-activated current (I(MI-CCAP)) and MCN1-activated current (I(MI-MCN1)) exhibit distinct time courses in LG during protraction. This distinction results from I(MI-CCAP) being regulated only by postsynaptic voltage, whereas I(MI-MCN1) is also regulated by LG presynaptic inhibition of MCN1. Hence, without CCAP, retraction and protraction duration are determined by the time course of I(MI-MCN1) buildup and feedback inhibition-mediated decay, respectively, in LG. With I(MI-CCAP) continually present, the impact of the feedback inhibition is reduced, prolonging protraction and maintaining retraction duration. Thus, comodulation of rhythmic motor activity can result from convergent activation, via distinct dynamics, of a single voltage-dependent current.

Author information

Author/s: DeLong, Nicholas D (ND); Kirby, Matthew S (MS); Blitz, Dawn M (DM); Nusbaum, Michael P (MP);

Affiliation: Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6074, USA.

Grants: F31-NS58013 (Agency:NINDS NIH HHS) ; R37-NS29436 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Sep; vol 29 (issue 39) : pp 12355-67

Dates: Created 2009/10/01; Completed 2009/10/13; Revised 2009/11/11;

PMID: 19793994, status: MEDLINE (last retrieval date: 11/12/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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