The Journal of Neurophysiology Vol. 80 No. 6 December 1998, pp. 3197-3213
Copyright ©1998 The American Physiological Society

Interaction of GABA_B-Mediated Inhibition With Voltage-Gated Currents of Pyramidal Cells: Computational Mechanism of a Sensory Searchlight

Neil J. Berman and Leonard Maler

Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario K1H 8M5, Canada

Berman, Neil J. and Leonard Maler. Interaction of GABA_B-mediated inhibition with voltage-gated currents of pyramidal cells: computational mechanism of a sensory searchlight. J. Neurophysiol. 80: 3197-3213, 1998. This study examines, in the in vitro electrosensory lateral line lobe (ELL) slice preparation, mono- and disynaptic inhibition in pyramidal cells evoked by stimulation of the direct descending pathway from nucleus praeminentialis (Pd). The pathway forms the stratum fibrosum (StF) in the ELL and consists of excitatory fibers from Pd stellate cells that make monosynaptic contact with pyramidal cells and disynaptic inhibitory contacts via local interneurons and of GABAergic inhibitory fibers from Pd bipolar cells. Single or tetanic stimulation (physiological rates of 100-200 Hz) of the StF produced excitatory postsynaptic potentials (EPSPs) or compound EPSPs in ELL pyramidal cells. Slow (>600 ms) and fast inhibitory postsynaptic potentials (IPSPs; 5-50 ms) also were evoked. Application of -aminobutyric acid-A (GABA_A) antagonists blocked the fast inhibition and dramatically increased the firing rate response to StF tetanic stimuli. GABA_A antagonists also increased the amplitude of the slow IPSP. The slow IPSP was reduced by GABA_B antagonists. Blockade of excitatory amino acid (EAA) synaptic transmission allowed the monosynaptic bipolar-cell-mediated inhibition to be studied in isolation: EAA antagonists blocked most of the EPSP response to StF stimulation leaving fast and (an increased amplitude) slow IPSP components. The bipolar-cell IPSPs were mediated by GABA_A and GABA_B receptors as they were sensitive to GABA_A and GABA_B antagonists. The bipolar-cell IPSPs scaled with stimulation rate (20-400 Hz), reaching a maximum amplitude at 200 Hz. Inhibitory efficacy of bipolar-cell slow IPSPs were tested by their ability to reduce spiking in the face of sustained or brief current pulses. Established spike trains (by sustained injected current) were little affected by the onset of the slow IPSP. Weak brief currents injected during the slow IPSP were strongly inhibited. Strong brief currents could overcome the slow IPSP inhibitory effect. Inhibition was observed to interact with the intrinsic I_A-like K⁺ currents to produce a complex control of cell spiking. Hyperpolarizing inhibition removes inactivation of I_A to prevent subsequent inputs from driving the cell to threshold. Established depolarizing inputs, having allowed I_A to inactivate, enable the cell to be highly sensitive to further depolarizing input. The term "conditional inhibition" is proposed to describe the general phenomenon where synaptic inhibition interacts with voltage-sensitive intrinsic currents.

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