Synaptic transmission in the auditory brainstem of normal and congenitally deaf mice.
The deafness (dn/dn) mutant mouse provides a valuable model of human congenital deafness. We investigated the properties of synaptic transmission in the anteroventral cochlear nucleus (AVCN) of normal and congenitally deaf dn/dn mice. Excitatory postsynaptic currents (EPSCs) were evoked by focal stimulation of single auditory nerve fibres, and measured by whole-cell recordings from neurones in AVCN slices (mean postnatal age = P13). Absolute amplitudes of both AMPA- and NMDA-mediated components of evoked EPSCs were greater (170 %) in deaf versus control animals. Enhanced transmission in deaf mice was due to a presynaptic mechanism. Variance-mean analysis revealed that the probability of transmitter release was significantly greater in deaf (P(r) = 0.8) versus control animals (P(r) = 0.5). Following high frequency stimulation, deaf mice showed a greater depression of evoked EPSCs, and a significant increase in the frequency of delayed-release (asynchronous) miniature EPSCs (aEPSCs) (deaf 100 Hz vs. control 7 Hz). The acetoxymethyl ester of EGTA (EGTA-AM) blocked the increase in miniature aEPSCs and returned tetanic depression to control values. In deaf mice, reduction of mean P(r) using cadmium caused an expected increase in paired-pulse ratio (PPR). However, in the same cells, a similar reduction in release by EGTA-AM did not result in a change in PPR, demonstrating that a change may occur in P(r) without a concomitant change in PPR. In many respects, transmission in deaf mice was found to be remarkably similar to control mice, implying that many parameters of synaptic transmission develop normally in these animals. The two significant differences (higher P(r) and asynchronous release in deaf mice) could both be reversed by the addition of EGTA-AM, suggesting that endogenous calcium buffering may be impaired or undeveloped in the presynaptic terminals of the auditory nerve in deaf mice.
Oleskevich
Sharon
S
Division of Neuroscience, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 0200, Australia.
Walmsley
Bruce
B
D000818:Animals; D001933:Brain Stem / Q000502:physiology*; D020864:Calcium Channels, N-Type / Q000502:physiology; D020907:Calcium Channels, Q-Type / Q000502:physiology; D002614:Chelating Agents / Q000494:pharmacology; D017626:Cochlear Nucleus / Q000502:physiology; D003638:Deafness / Q000151:congenital* / Q000503:physiopathology*; D004424:Ear Canal / Q000502:physiology; D004533:Egtazic Acid / Q000494:pharmacology; D004558:Electric Stimulation; D004594:Electrophysiology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008818:Mice, Neurologic Mutants; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects; D009435:Synaptic Transmission / Q000502:physiology*
D020864:Calcium Channels, N-Type; D020907:Calcium Channels, Q-Type; D002614:Chelating Agents; D015221:Potassium Channels; D004533:Egtazic Acid