Spontaneous rhythmic bursts induced by pharmacological block of inhibition in lumbar motoneurons of the neonatal rat spinal cord

Abstract

1. The effects of blocking gamma-aminobutyric acid- and glycine-mediated synaptic transmission by bicuculline and strychnine on the neonatal rat isolated spinal cord were investigated by intracellular recording from motoneurons with the use of current-clamp and voltage-clamp techniques and by extracellular recording from homologous ventral roots of the L5 segment. 2. Bicuculline per se evoked irregular bursts of motoneuron membrane potential, often comprising individual events fused together. Strychnine alone did not elicit spontaneous bursting in the large majority of preparations. Simultaneous application of bicuculline and strychnine consistently induced regular rhythmic bursts (frequency approximately 2 per min, duration approximately 7 s), comprising a rapid depolarization followed by large-amplitude oscillations. 3. Burst frequency, duration, and intraburst oscillation time course were independent of motoneuron membrane potential. Burst and oscillation amplitude decreased with membrane depolarization and, under voltage-clamp conditions, inverted polarity near 0 mV. 4. The regular bursts produced by bicuculline and strychnine were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione, tetrodotoxin, or Cd2+. 5. N-methyl-D-aspartate antagonists [R-5-aminophosphonovalerate or 3-((RS)-2-carboxypiperazine-4-yl)-propyl-1-phosphonate (CPP)] reversibly blocked or slowed down bursting induced by bicuculline and strychnine. Addition of cyclothiazide to the bicuculline and strychnine solution increased bursting frequency while preserving the regular burst structure; under these conditions bursts became insensitive to CPP. 6. In the presence of bicuculline and strychnine, 5-hydroxytryptamine (5-HT) increased burst frequency and decreased burst duration in a dose-dependent fashion. 7. In the presence of bicuculline and strychnine, L5 ventral roots developed synchronous rhythmic activity with a time course similar to that recorded from individual motoneurons. The rhythmic activity was accelerated by 5-HT on both roots, in accordance with observations on single motoneurons. 8. Rhythmic bursts thus appear to result from large, synchronous synaptic events generated by a network modulated by 5-HT and highly sensitive to variations in efficacy of glutamatergic synaptic transmission. These results show that in the rat spinal cord highly patterned motor output can occur despite block of inhibition.

Primary Afferent Terminals Acting as Excitatory Interneurons Contribute to Spontaneous Motor Activities in the Immature Spinal Cord

“…2a, compare bottom traces). Such rhythmic motor activities produced by disinhibited networks have been extensively studied (Bracci et al, 1996). In the remaining two of six preparations, no activity recovered.…”

Noradrenaline Unmasks Novel Self-Reinforcing Motor Circuits within the Mammalian Spinal Cord

“…As demonstrated previously, blockade of GABAergic and glycinergic inhibitory transmission results in the emergence of spontaneous synchronous bursting in motor pools from all recorded ventral roots (Bracci et al, 1996). We examined whether activating recurrent collaterals could affect this bursting but were unable to detect any changes in animals younger than P9 (n ϭ 10).…”

“…Blockade of synaptic inhibition can induce spontaneous epileptiform bursting in several CNS regions, including the cortex, hippocampus, and spinal cord (Hablitz, 1984;Hwa and Avoli, 1991;Bracci et al, 1996). Because cortex and hippocampus both have recurrent excitatory connections, we investigated whether recurrent excitatory pathways are also involved in spontaneous bursting activity in this preparation.…”

Role of the Electrogenic Na/K Pump in Disinhibition-Induced Bursting in Cultured Spinal Networks

“…The former is commonly induced by excitatory transmitters like NMDA and 5-HT and involves alternation between left and right and between flexors and extensors (Cazalets et al 1990; Kiehn and Kjaerulff 1998;Kudo and Yamada 1987). The latter is induced by removing synaptic inhibition pharmacologically (disinhibition) and is characterized by a synchronous slow bursting (Bracci et al 1996;Cowley and Schmidt 1995). Although fictive locomotion requires at least a few intact spinal segments (Ballion et al 2001; but see also Demir et al 2002), disinhibition-induced bursting is also seen in slice cultures and dissociated cultures of the spinal cord (Ballerini and Galante 1998;Streit 1993;Tscherter et al 2001).…”