Search

Bicuculline is the most commonly used GABA(A) receptor antagonist to investigate the contribution of these receptors in motor control. However, this compound has been shown recently to potentiate the burst firing of neurons in various brain regions by blocking a calcium-activated potassium current underlying the spike after-hyperpolarization (AHP). This effect may distort our understanding of the role of GABA(A) receptors at the network level. In vitro brainstem-spinal cord preparations isolated from neonatal rats were used to compare the effects of bicuculline methiodide (bicuculline-M) and picrotoxin (PTX), another GABA(A) receptor antagonist, on the AHP of lumbar motoneurons as well as on spontaneous and locomotor-like motor activities. Intracellular recordings of lumbar motoneurons showed that bicuculline-M (20 microM) reduced the AHP to 57% of control whereas PTX (20-60 microM) had no significant effect. Bath-application of increasing concentrations of PTX caused an increase in spontaneous ventral root activity, which further increased significantly when bicuculline-M was added. The effects of both antagonists were tested on fictive locomotion. The left-right alternation was disrupted in the presence of bicuculline-M. A slow synchronous bursting activity of large amplitude also appeared in the presence of PTX. This slow rhythm was superimposed on a faster rhythm which still exhibited some degree of left-right alternation. These data demonstrate that bicuculline-M may not reveal accurately the contribution of GABA(A) receptors in motor control and the intrinsic properties of disinhibited networks.

Lamprey reticulospinal neurons show phasic oscillations of their membrane potential during fictive locomotion. This modulation originates from the spinal cord locomotor networks. The aim of the present study was to elucidate the pattern of discharge of the spino-bulbar axons responsible for this modulation. Experiments were performed on in vitro brainstem/spinal cord preparations. Two baths were formed in the recording chamber. The caudal one was perfused with 150 μMN-methyl- d -aspartate (NMDA) solution to induce fictive locomotion. The rostral bath containing the brain and the first 3–5 segments of the spinal cord was exposed to a 0 Ca2+ + 2.6 mM Mn2+ solution to block synaptic transmission and therefore to abolish any rhythmic descending activity. Spinobulbar axons were recorded intracellularly at the level of the brain/spinal cord junction. They exhibited phasic discharges correlated with the ongoing motor activity in the caudal pool. Some discharged in phase with either the ipsilateral or the contralateral ventral root bursts, others with either of the transition phases between these two bursts. These spinal cells with ascending axons, running in the ventrolateral spinal cord, may be important for modulating the activity of supraspinal neurons to match the ongoing locomotor activity.