Synaptic refinement of an inhibitory topographic map in the auditory brainstem requires functional Cav1.3 calcium channels

Synaptic refinement via the elimination of inappropriate synapses and strengthening of appropriate ones is crucially important for the establishment of specific, topographic neural circuits. The mechanisms driving these processes are poorly understood, particularly concerning inhibitory projections....

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Bibliographic Details
Published in:The Journal of neuroscience 2012-10, Vol.32 (42), p.14602-14616
Main Authors: Hirtz, Jan J, Braun, Nadine, Griesemer, Désirée, Hannes, Christian, Janz, Katrin, Löhrke, Stefan, Müller, Britta, Friauf, Eckhard
Format: Article
Language:English
Subjects:
Animals
Brain Mapping - methods
Brain Stem - metabolism
Brain Stem - physiology
Calcium Channels, L-Type - deficiency
Calcium Channels, L-Type - physiology
Evoked Potentials, Auditory, Brain Stem - physiology
Female
Inhibitory Postsynaptic Potentials - physiology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neural Inhibition - genetics
Neural Inhibition - physiology
Organ Culture Techniques
Phenotype
Synapses - genetics
Synapses - physiology
Synaptic Transmission - genetics
Synaptic Transmission - physiology
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Summary:Synaptic refinement via the elimination of inappropriate synapses and strengthening of appropriate ones is crucially important for the establishment of specific, topographic neural circuits. The mechanisms driving these processes are poorly understood, particularly concerning inhibitory projections. Here, we address the refinement of an inhibitory topographic projection in the auditory brainstem in functional and anatomical mapping studies involving patch-clamp recordings in combination with minimal and maximal stimulation, caged glutamate photolysis, and single axon tracing. We demonstrate a crucial dependency of the refinement on Ca(V)1.3 calcium channels: Ca(V)1.3(-/-) mice displayed virtually no elimination of projections up to hearing onset. Furthermore, strengthening was strongly impaired, in line with a reduced number of axonal boutons. The mediolateral topography was less precise and the shift from a mixed GABA/glycinergic to a purely glycinergic transmission before hearing onset did not occur. Together, our findings provide evidence for a Ca(V)1.3-dependent mechanism through which both inhibitory circuit formation and determination of the neurotransmitter phenotype are achieved.
ISSN:1529-2401
0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.0765-12.2012