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. 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.
Animal Physiology Group, Department of Biology, University of Kaiserslautern, D-67653 Kaiserslautern, Germany.
Jan J
JJ
Hirtz
Nadine
N
Braun
Désirée
D
Griesemer
Christian
C
Hannes
Katrin
K
Janz
Stefan
S
Löhrke
Britta
B
Müller
Eckhard
E
Friauf
D000818:Animals; D001931:Brain Mapping / Q000379:methods; D001933:Brain Stem / Q000378:metabolism / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000172:deficiency / Q000502:physiology*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005260:Female; D053444:Inhibitory Postsynaptic Potentials / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000235:genetics / Q000502:physiology*; D009924:Organ Culture Techniques; D010641:Phenotype; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology
C485995:Cacna1d protein, mouse; D020746:Calcium Channels, L-Type