Spontaneous Network Activity Transiently Depresses Synaptic Transmission in the Embryonic Chick Spinal Cord

Abstract

We examined the effects of spontaneous or evoked episodes of rhythmic activity on synaptic transmission in several spinal pathways of embryonic day 9-12 chick embryos. We compared the amplitude of synaptic potentials evoked by stimulation of the ventrolateral funiculus (VLF), the dorsal or ventral roots, before and after episodes of activity. With the exception of the short-latency responses evoked by dorsal root stimulation, the potentials were briefly potentiated and then reduced for several minutes after an episode of rhythmic activity. Their amplitude progressively recovered in the interval between successive episodes. The lack of post-episode depression in the shortlatency component of the dorsal root evoked responses is probably attributable to the absence of firing in cut muscle afferents during an episode of activity.The post-episode depression of VLF-evoked potentials was mimicked by prolonged stimulation of the VLF, subthreshold for an episode of activity. By contrast, antidromically induced motoneuron firing and the accompanying calcium entry did not depress VLF-evoked potentials recorded from the stimulated ventral root. In addition, post-episode depression of VLFevoked synaptic currents was observed in voltage-clamped spinal neurons. Collectively, these findings suggest that somatic postsynaptic activity and calcium entry are not required for the depression. We propose instead that the mechanism may involve a form of long-lasting activity-induced synaptic depression, possibly a combination of transmitter depletion and ligand-induced changes in the postsynaptic current accompanying transmitter release. This activity-dependent depression appears to be an important mechanism underlying the occurrence of spontaneous activity in developing spinal networks.

Modeling Spontaneous Activity in the Developing Spinal Cord Using Activity-Dependent Variations of Intracellular Chloride

“…Because these experiments were performed in the presence of glutamatergic and cholinergic blockers, we assumed that the responses we were recording were predominantly GABA/ glycinergic. Also, because synaptic responses are depressed after an episode (Fedirchuk et al, 1999), we waited several minutes after an episode before applying the antagonist, thus ensuring that the evoked response had recovered. We then compared the averaged response taken after the antagonist application with the one right before the application, by measuring the amplitude within 5 ms of the onset, to include only the monosynaptic component (see Materials and Methods).…”

“…Spontaneous activity is an important property of the developing nervous system (Katz and Shatz, 1996;O'Donovan, 1999). It usually involves episodes of rhythmic discharge, during which many neurons are activated synchronously, separated by longer quiescent periods.…”

“…It has been proposed that spontaneous activity is generated in hyperexcitable networks that are subject to some form of activitydependent depression (Feller et al, 1999;O'Donovan, 1999;Opitz et al, 2002). During development, the classical inhibitory neurotransmitters GABA and glycine can be functionally excitatory because the chloride equilibrium potential is above rest as a result of an elevated intracellular chloride concentration (Chub and O'Donovan, 2001) (for review, see Ben Ari, 2002).…”

“…This leads to a predominance of excitatory synapses that renders developing networks hyperexcitable. We proposed that, in the chick embryo spinal cord, a fast form of depression, operating on a timescale Ͻ1 s, regulates cycle generation within the episodes, whereas a much slower form of depression (timescale of minutes) regulates the expression of episodes (Fedirchuk et al, 1999;Tabak et al, 2000). This prolonged time course of the slow depression (from a few minutes to more than 30 min) is highly unusual and cannot be explained by traditional forms of synaptic depression (e.g., transmitter depletion) or channel inactivation, which are much faster (Varela et al, 1997).…”

Activity-Dependent Plasticity of Descending Synaptic Inputs to Spinal Motoneurons in anIn VitroTurtle Brainstem–Spinal Cord Preparation

“…For example, long-lasting (Ͼ30 min) activity-dependent plasticity is expressed in corticospinal inputs to spinal interneurons (Iriki et al, 1990), afferent inputs to spinal motoneurons (for review, see Wolpaw, 1997) and dorsal horn neurons (for review, see Randic, 1996), and the neuromuscular junction (Wan and Poo, 1999). Likewise, short-term (Ͻ30 min) activity-dependent plasticity in the spinal cord is hypothesized to be an important mechanism regulating the expression of rhythmic locomotor activity in the chick (O'Donovan and Rinzel, 1997;Fedirchuk et al, 1999) and lamprey (Parker and Grillner, 1999). It is well established that spinal plasticity is an important feature of recovery from spinal cord injury (Durkovic, 1986;Hodgson et al, 1994;Muir and Steeves, 1997) (also see Carrier et al, 1997), and it is likely that activity-dependent spinal plasticity is one of several mechanisms contributing to such recovery.…”