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[Abstract Title]. - Society for Neuroscience

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Topic: D.02.a. Mechanoreceptors and cochlea<br />

Support: BMBF Grant to TM and AN<br />

DFG Fellowship to NS<br />

Jack Kent Cooke Foundation<br />

NIDCD Grant P30 DC 00529 to MCL<br />

NIDCD Grant RO1 DC 00188 to MCL<br />

<strong>Title</strong>: Synaptic ribbons in cochlear hair cells are required <strong>for</strong> reliable coding of stimulus onset<br />

Authors: *B. N. BURAN 1,2 , N. STRENZKE 3,2 , A. NEEF 4 , T. MOSER 3,4 , M. C.<br />

LIBERMAN 1,5,2 ;<br />

1 Div. of Hlth. Sci. and Technol., Harvard-MIT, Cambridge, MA; 2 Eaton-Peabody Lab.,<br />

Massachusetts Eye and Ear Infirmary, Boston, MA; 3 Inner Ear Lab, Dept. of Otolaryngology,<br />

4 Bernstein Ctr. <strong>for</strong> Computat. Neurosci., Univ. of Goettingen, Goettingen, Germany; 5 Dept. of<br />

Otology and Laryngology, Harvard Med. Sch., Boston, MA<br />

<strong>Abstract</strong>: Synaptic ribbons are electron-dense structures surrounded by vesicles and tethered to<br />

the presynaptic membrane of photoreceptors, retinal bipolar cells and hair cells. Such synapses<br />

are characterized by sustained exocytosis that is graded with stimulus intensity and can achieve<br />

very high rates of release.<br />

To gain insight into the function of this specialized presynaptic machinery, we characterized the<br />

response properties of single auditory nerve (AN) fibers in a mouse with targeted deletion of<br />

bassoon, the gene <strong>for</strong> a presynaptic scaffolding protein, in which synaptic ribbons are no longer<br />

tethered to the active zone. Prior in vitro studies showed a strong reduction of hair cell<br />

exocytosis in these mutants. While in<strong>for</strong>mative, whole-cell responses reflect the summed activity<br />

of many synapses, which are heterogeneous with respect to spontaneous and sound-evoked rates.<br />

Since each mammalian AN fiber receives input from a single inner hair cell active zone, to<br />

which, typically, a single ribbon is tethered, single-fiber recordings in bassoon mutants and<br />

control mice offer a sensitive functional metric of the contribution of individual synaptic ribbons.<br />

Response properties of mutant AN fibers were similar, in many respects, to wild-type. Spike<br />

intervals retained their normal irregularity, thresholds were unaffected, dynamic range was<br />

unchanged, spike synchronization to stimulus phase was unimpaired, post-onset adaptation and<br />

recovery from adaptation were normal, and the ability to sustain discharge throughout a longduration<br />

stimulus was unaffected. However, striking abnormalities were seen in absolute<br />

discharge rates. Mean spontaneous rate was decreased by a factor of 4 and sound-evoked rates<br />

were decreased by a factor of 2. A corresponding increase was observed in the variance of the<br />

first spike latency in response to moderate level tone bursts. This increased jitter likely arises<br />

from a reduction in synaptic drive through a mechanism such as decreased probability of<br />

simultaneous vesicle release, and may degrade the ability of the auditory system to resolve<br />

stimulus features such as interaural time differences that mediate sound localization and other<br />

key aspects of binaural hearing.

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