In:
eLife, eLife Sciences Publications, Ltd, Vol. 5 ( 2016-07-12)
Abstract:
The brain contains billions of nerve cells, or neurons, that communicate with one another through connections called synapses. As the brain develops, these circuits are extensively modified as new synapses are created and others are removed. Neurological disorders may emerge if these processes are not regulated correctly. Identifying the biological pathways that control the addition and removal of synapses could therefore provide new insights into how to treat human brain diseases. To communicate across a synapse, the signaling neuron releases chemicals called neurotransmitters that alter the activity of the receiving neuron. Some neurotransmitters, such as GABA, inhibit the activity of the receiving neuron. The activity of a neuron – and hence how often it releases neurotransmitters – depends on different ions moving into and out of the neuron through proteins called ion channels that are embedded in the cell membrane. For example, the movement of calcium ions into the neuron can trigger the release of neurotransmitters. The roundworm Caenorhabditis elegans is often used as a model organism to study how the brain develops. During development, the worm nervous system eliminates synapses that release GABA and reassembles them at new locations. However, the nervous system does not eliminate these synapses at random. Miller-Fleming, Petersen et al. now show that a C. elegans protein called UNC-8 is responsible for this effect. UNC-8 forms part of an ion channel that allows sodium ions to enter the neuron and is selectively produced in GABA neurons that are destined for remodeling. Miller-Fleming, Petersen et al. found that inside GABA-releasing neurons, calcium ions stimulate an enzyme called calcineurin that may in turn activate UNC-8. Sodium ions then enter the neuron through UNC-8 channels. This boosts the activity of the calcium ion channels, which further increases how many calcium ions enter the cell. Ultimately, the amount of calcium inside the neuron becomes high enough to activate an additional pathway that eliminates the synapse. This downstream pathway involves components of a cell-killing (or “apoptotic”) mechanism that is repurposed in this case to remove the GABA release apparatus at the synapse. Other proteins are likely to help UNC-8 sense the activity of neurons and destroy synapses in response. Further work is required to investigate these additional components and to determine how they work with UNC-8 to remove synapses in the nervous system during development.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.14599.001
DOI:
10.7554/eLife.14599.002
DOI:
10.7554/eLife.14599.003
DOI:
10.7554/eLife.14599.004
DOI:
10.7554/eLife.14599.005
DOI:
10.7554/eLife.14599.006
DOI:
10.7554/eLife.14599.007
DOI:
10.7554/eLife.14599.008
DOI:
10.7554/eLife.14599.009
DOI:
10.7554/eLife.14599.010
DOI:
10.7554/eLife.14599.011
DOI:
10.7554/eLife.14599.012
DOI:
10.7554/eLife.14599.013
DOI:
10.7554/eLife.14599.014
DOI:
10.7554/eLife.14599.015
DOI:
10.7554/eLife.14599.016
DOI:
10.7554/eLife.14599.017
DOI:
10.7554/eLife.14599.018
DOI:
10.7554/eLife.14599.019
DOI:
10.7554/eLife.14599.020
DOI:
10.7554/eLife.14599.021
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2016
detail.hit.zdb_id:
2687154-3
