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Mechanisms underlying spontaneous patterned activity in developing neural circuits

Key Points

  • During development, several different circuits of the CNS spontaneously generate correlated firing patterns that are distinct from activity patterns observed in the mature state.

  • The spontaneously active circuits described here are the spinal cord, cochlea, retina, hippocampus and cerebellum.

  • Although spontaneously active circuits have unique architectures, they use similar strategies to generate activity.

  • One of the common features is the existence of transient excitatory networks, consisting of depolarizing GABA (γ-aminobutyric acid), transient synaptic connections or gap junction coupling.

  • Another common feature is the presence of pacemaker-like neurons that are involved in the spontaneous generation of events.

  • There are many examples in which the absence of a crucial network component leads to the generation of spontaneous correlated activity by a compensatory circuit. This indicates that a given region of the CNS can use multiple strategies to generate spontaneous activity.

Abstract

Patterned, spontaneous activity occurs in many developing neural circuits, including the retina, the cochlea, the spinal cord, the cerebellum and the hippocampus, where it provides signals that are important for the development of neurons and their connections. Despite there being differences in adult architecture and output across these various circuits, the patterns of spontaneous network activity and the mechanisms that generate it are remarkably similar. The mechanisms can include a depolarizing action of GABA (γ-aminobutyric acid), transient synaptic connections, extrasynaptic transmission, gap junction coupling and the presence of pacemaker-like neurons. Interestingly, spontaneous activity is robust; if one element of a circuit is disrupted another will generate similar activity. This research suggests that developing neural circuits exhibit transient and tunable features that maintain a source of correlated activity during crucial stages of development.

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Figure 1: Homeostatic regulation of spontaneous network activity in the chick spinal cord.
Figure 2: Homeostatic regulation of spontaneous network activity in the mammalian retina.

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Acknowledgements

Support provided by National Science Foundation grant IOS-0818983 (M.F.) and US National Institutes of Health grants RO1EY013528 (M.F.) and F31NS058167 (A.B.). The authors thank D. Bergles and P. Wenner for critical comments on the manuscript.

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Correspondence to Marla B. Feller.

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Spontaneous network activity in a postnatal day 10 mouse retina. (MOV 9445 kb)

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Glossary

Extrasynaptic transmission

Neurotransmitter-mediated signalling through a pathway other than a direct synaptic connection. One example is spillover, in which synaptically released neurotransmitter diffuses out of the synapse and activates extrasynaptic receptors or synaptic receptors located in neighbouring synapses. A second example is volume transmission, in which neurotransmitter is released directly into the non-synaptic extracellular space.

Gap junctions

Intercellular channels composed of connexin proteins that are the basis of electrical synapses between neurons.

Retinal ganglion cells

The projection neurons of the retina, the axons of which form the optic nerve.

Central pattern generator

A neural circuit that produces self-sustaining patterns of behaviour independently of sensory input.

Pacemaker-like neuron

In the adult nervous system, pacemaker neurons possess a set of ion channels that lead to regular patterns of depolarization and hyperpolarization. In developing circuits, pacemaker-like neurons are neurons with unstable membrane potentials, the pacemaker properties of which also depend on network interactions.

Amacrine cell

A retinal interneuron located in the inner nuclear or ganglion cell layer of the retina that provides local inhibition in the adult retina.

Renshaw cell

A GABAergic interneuron that receives excitatory input from motor neurons.

Bipolar cell

An interneuron of the retina that provides excitatory glutamatergic input to retinal ganglion cells. In the adult retina, bipolar cells receive input from photoreceptors.

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Blankenship, A., Feller, M. Mechanisms underlying spontaneous patterned activity in developing neural circuits. Nat Rev Neurosci 11, 18–29 (2010). https://doi.org/10.1038/nrn2759

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