Mechanisms of spontaneous activity in developing spinal networks

Abstract

Developing networks of the chick spinal cord become spontaneously active early in development and remain so until hatching. Experiments using an isolated preparation of the spinal cord have begun to reveal the mechanisms responsible for this activity. Whole‐cell and optical recordings have shown that spinal neurons receive a rhythmic, depolarizing synaptic drive and experience rhythmic elevations of intracellular calcium during spontaneous episodes. Activity is expressed throughout the neuraxis and can be produced by different parts of the cord and by the isolated brain stem, suggesting that it does not depend upon the details of network architecture. Two factors appear to be particularly important for the production of endogenous activity. The first is the predominantly excitatory nature of developing synaptic connections, and the second is the presence of prolonged activity‐dependent depression of network excitability. The interaction between high excitability and depression results in an equilibrium in which episodes are expressed periodically by the network. The mechanism of the rhythmic bursting within an episode is not understood, but it may be due to a “fast” form of network depression. Spontaneous embryonic activity has been shown to play a role in neuron and muscle development, but is probably not involved in the initial formation of connections between spinal neurons. It may be important in refining the initial connections, but this possibility remains to be explored. © 1998 John Wiley & Sons, Inc. J Neurobiol 37: 131–145, 1998

Glycine Release from Radial Cells Modulates the Spontaneous Activity and Its Propagation during Early Spinal Cord Development

“…Such spontaneous activity is thought to be initiated by nonsynaptic transmitter release during early development and then synaptically at later stages (O'Donovan, 1999;Ben-Ari et al, 2004). Although the mechanisms of synaptically driven spontaneous activity have yet to be elucidated, it is clear that many excitatory neurotransmitters are involved in the genesis of these bursts (O'Donovan et al, 1998) and that activitydependent network depression likely allows the periods of quiescence between bursts (Tabak et al, 2001). Spontaneous electrical activity that occurs at early stages of development before and during the formation of synaptic networks is needed for neuronal proliferation, migration, and differentiation (Spitzer, 2006).…”

Compensatory changes in cellular excitability, not synaptic scaling, contribute to homeostatic recovery of embryonic network activity

“…SNA is produced by hyperexcitable, recurrently connected circuits in which both GABA and glutamate are excitatory. In the developing spinal cord, SNA has been shown to be important for various aspects of limb (13) and motoneuron (14)(15)(16) development. We have shown recently that when SNA was reduced for 48 h in vivo, compensatory increases in AMPA and GABA A quantal amplitude were triggered, suggesting that homeostatic synaptic plasticity contributed to the maintenance of SNA (9).…”

The development of potentially better practices to support the neurodevelopment of infants in the NICU

“…6,11 -17 Once this initial configuration of neurons is established, there are two major stimulus-driven processes that are essential for the development, organization and modeling of neural circuits: endogenous or activity-independent and exogenous or activity-dependent stimulation. [18][19][20][21][22] Endogenous stimulation. Research on the development of the human visual system has provided great insight into this process.…”

“…Gamma-aminobutyric acid, which, with maturation, will become a primary central nervous system inhibitory neurotransmitter, early in development, functions as an excitatory neurotransmitter. This increased excitatory stimulus in early development favors development of endogenous waves of spontaneously firing neural networks [21][22][23][24] also called early network oscillations 21 or giant depolarizing potentials. 23 These neuronal discharges will originate in multiple areas of the brain and function at three levels of maturation:…”

“…This will occur at different times for each sensory system and are associated with the targeting of axons from ganglion cells of the retina, cochlea, cerebellum, hippocampus, thalamus, superior colliculus and spinal cord. 21,22 They are essential for the accurate targeting of neuronal axons to the sensory receptors, that is, eye, ear, skin and other tissues to relay nuclei and thus to the cortex. They are presumably active for the somatesthetic (touch), kinesthetic and proprioceptive systems as early as 24 to 25 weeks gestation.…”