Abstract
The medial nucleus of the trapezoid body (MNTB) is an important source of inhibition during the computation of sound location. It transmits fast and precisely timed action potentials at high frequencies; this requires an efficient calcium clearance mechanism, in which plasma membrane calcium ATPase 2 (PMCA2) is a key component. Deafwaddler (dfw2J ) mutant mice have a null mutation in PMCA2 causing deafness in homozygotes (dfw2J /dfw2J ) and high-frequency hearing loss in heterozygotes (+/dfw2J ). Despite the deafness phenotype, no significant differences in MNTB volume or cell number were observed in dfw2J homozygous mutants, suggesting that PMCA2 is not required for MNTB neuron survival. The MNTB tonotopic axis encodes high to low sound frequencies across the medial to lateral dimension. We discovered a cell size gradient along this axis: lateral neuronal somata are significantly larger than medially located somata. This size gradient is decreased in +/dfw2J and absent in dfw2J /dfw2J The lack of acoustically driven input suggests that sound-evoked activity is required for maintenance of the cell size gradient. This hypothesis was corroborated by selective elimination of auditory hair cell activity with either hair cell elimination in Pou4f3 DTR mice or inner ear tetrodotoxin (TTX) treatment. The change in soma size was reversible and recovered within 7 days of TTX treatment, suggesting that regulation of the gradient is dependent on synaptic activity and that these changes are plastic rather than permanent.NEW & NOTEWORTHY Neurons of the medial nucleus of the trapezoid body (MNTB) act as fast-spiking inhibitory interneurons within the auditory brain stem. The MNTB is topographically organized, with low sound frequencies encoded laterally and high frequencies medially. We discovered a cell size gradient along this axis: lateral neurons are larger than medial neurons. The absence of this gradient in deaf mice lacking plasma membrane calcium ATPase 2 suggests an activity-dependent, calcium-mediated mechanism that controls neuronal soma size.
Highlights
NEW & NOTEWORTHY Neurons of the medial nucleus of the trapezoid body (MNTB) act as fast-spiking inhibitory interneurons within the auditory brain stem
The excitatory input to the lateral superior olive (LSO) is direct, the inhibitory circuit includes a signal inversion upon transmission through the medial nucleus of the trapezoid body (MNTB)
PMCA2 is clearly present in the calyx, indicating that it is involved in presynaptic calcium clearance
Summary
NEW & NOTEWORTHY Neurons of the medial nucleus of the trapezoid body (MNTB) act as fast-spiking inhibitory interneurons within the auditory brain stem. The excitatory input to the LSO is direct, the inhibitory circuit includes a signal inversion upon transmission through the medial nucleus of the trapezoid body (MNTB) These projections must converge in temporal register (Tollin 2003) and require fast transmission in the globular bushy cellMNTB pathway to compensate for the additional synapse (Taschenberger and von Gersdorff 2000; Wang et al 1998). MNTB neurons are driven by large glutamatergic synapses, the calyces of Held (Schneggenburger and Forsythe 2006; von Gersdorff and Borst 2002), and can sustain in vivo instantaneous firing rates of Ͼ300 spikes/s (Kopp-Scheinpflug et al 2008) With such high firing frequencies, presynaptic residual calcium must be cleared rapidly to avoid synaptic facilitation and/or depression. We discovered a tonotopically organized cell size gradient in the MNTB that is regulated by sound-evoked activity and is absent in deaf PMCA2 mutants
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