Faculty Collaboration Database

Differential processing of excitation by GABAergic gain modulation in canine caudal ventral respiratory group neurons. J Neurophysiol 2003 Feb;89(2):862-70

Date

02/08/2003

Pubmed ID

12574464

DOI

10.1152/jn.00761.2002

Scopus ID

2-s2.0-0037319226 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

The discharge frequency (F(n)) patterns of medullary respiratory premotor neurons are subject to potent tonic GABAergic gain modulation. Studies in other neuron types suggest that the synaptic input for tonic inhibition is located on the soma where it can affect total neuronal output. However, our preliminary data suggested that excitatory responses elicited by highly local application of glutamate receptor agonists are not gain modulated. In addition, modulation of the amplitude of spike afterhyperpolarizations can gain modulate neuronal output, and this mechanism is located near the spike initiation zone and/or soma. The purpose of this study was to determine if these two gain-modulating mechanisms have different functional locations on the somatodendritic membrane of bulbospinal inspiratory and expiratory neurons. Four-barrel micropipettes were used for extracellular single-neuron recording and pressure ejection of drugs in decerebrate, paralyzed, ventilated dogs. The net increases in F(n) due to repeated short-duration picoejections of the glutamate receptor agonist, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), was quantified before and during locally induced antagonism of GABA(A) receptors by bicuculline or small-conductance, calcium-activated potassium channels by apamin. The AMPA-induced net increases in F(n) were not significantly altered by BIC, although it produced large increases in the respiratory-related activity. However, the AMPA-induced net responses were amplified in accordance with the gain increase of the respiratory-related activity by apamin. These findings suggest that GABAergic gain modulation may be functionally isolated from the soma/spike initiation zone, e.g., located on a dendritic shaft. This could allow other behavioral signals requiring strong neuronal activation (e.g., coughing, sneezing, vomiting) to utilize the same neuron without being attenuated by the GABAergic modulation.

Author List

Tonkovic-Capin V, Stucke AG, Stuth EA, Tonkovic-Capin M, Hopp FA, McCrimmon DR, Zuperku EJ

Authors

Astrid G. Stucke MD Professor in the Anesthesiology department at Medical College of Wisconsin
Eckehard A. Stuth MD Professor in the Anesthesiology department at Medical College of Wisconsin
Edward J. Zuperku PhD Professor in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Action Potentials
Animals
Apamin
Bicuculline
Dendrites
Dogs
Excitatory Amino Acid Agonists
Female
GABA Antagonists
Male
Neurons
Respiratory Center
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
gamma-Aminobutyric Acid