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Spontaneous activity promotes synapse formation in a cell-type-dependent manner in the developing retina.
- Source :
-
The Journal of neuroscience : the official journal of the Society for Neuroscience [J Neurosci] 2012 Apr 18; Vol. 32 (16), pp. 5426-39. - Publication Year :
- 2012
-
Abstract
- Spontaneous activity is thought to regulate synaptogenesis in many parts of the developing nervous system. In vivo evidence for this regulation, however, is scarce and comes almost exclusively from experiments in which normal activity was reduced or blocked completely. Thus, whether spontaneous activity itself promotes synaptogenesis or plays a purely permissive role remains uncertain. In addition, how activity influences synapse dynamics to shape connectivity and whether its effects among neurons are uniform or cell-type-dependent is unclear. In mice lacking the cone-rod homeobox gene (Crx), photoreceptors fail to establish normal connections with bipolar cells (BCs). Here, we find that retinal ganglion cells (RGCs) in Crx⁻/⁻ mice become rhythmically hyperactive around the time of eye opening as a result of increased spontaneous glutamate release from BCs. This elevated neurotransmission enhances synaptogenesis between BCs and RGCs, without altering the overall circuit architecture. Using live imaging, we discover that spontaneous activity selectively regulates the rate of synapse formation, not elimination, in this circuit. Reconstructions of the connectivity patterns of three BC types with a shared RGC target further revealed that neurotransmission specifically promotes the formation of multisynaptic appositions from one BC type without affecting the maintenance or elimination of connections from the other two. Although hyperactivity in Crx⁻/⁻ mice persists, synapse numbers do not increase beyond 4 weeks of age, suggesting closure of a critical period for synaptic refinement in the inner retina. Interestingly, despite their hyperactivity, RGC axons maintain normal eye-specific territories and cell-type-specific layers in the dorsal lateral geniculate nucleus.
- Subjects :
- Action Potentials genetics
Age Factors
Animals
Animals, Newborn
Biophysics
Calbindins
Calcium Channels metabolism
Calcium Channels, L-Type
Cholera Toxin administration & dosage
Cholera Toxin metabolism
Choline O-Acetyltransferase metabolism
Disks Large Homolog 4 Protein
Electric Stimulation methods
Excitatory Postsynaptic Potentials genetics
Eye anatomy & histology
Female
Gene Expression Regulation, Developmental genetics
Geniculate Bodies cytology
Geniculate Bodies physiology
Guanylate Kinases genetics
Guanylate Kinases metabolism
Homeodomain Proteins
Injections, Intraocular methods
Luminescent Proteins genetics
Luminescent Proteins metabolism
Membrane Proteins genetics
Membrane Proteins metabolism
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neurogenesis genetics
Neurotransmitter Agents metabolism
Patch-Clamp Techniques
Peanut Agglutinin metabolism
Periodicity
Presynaptic Terminals physiology
Receptors, Dopamine D4 genetics
Retinal Ganglion Cells cytology
Retinal Ganglion Cells physiology
Rhodopsin metabolism
S100 Calcium Binding Protein G metabolism
Trans-Activators deficiency
Transfection
Vesicular Glutamate Transport Protein 1 metabolism
Visual Pathways cytology
Visual Pathways physiology
Action Potentials physiology
Neurons classification
Neurons cytology
Retina cytology
Retina growth & development
Synapses physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2401
- Volume :
- 32
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 22514306
- Full Text :
- https://doi.org/10.1523/JNEUROSCI.0194-12.2012