J Neurophysiol (February 1, 2003). 10.1152/jn.00761.2002
Submitted on Submitted 5 September 2002; accepted in final form 20 October 2002

Differential Processing of Excitation by GABAergic Gain Modulation in Canine Caudal Ventral Respiratory Group Neurons

 ¹Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295;  ²Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226; and  ³Department of Physiology and Institute for Neuroscience, Northwestern University Medical School, Chicago, Illinois 60611

Tonkovic-Capin, V., A. G. Stucke, E. A. Stuth, M. Tonkovic-Capin, F. A. Hopp, D. R. McCrimmon, and E. J. Zuperku. Differential Processing of Excitation by GABAergic Gain Modulation in Canine Caudal Ventral Respiratory Group Neurons. J. Neurophysiol. 89: 862-870, 2003. 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, -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.