TY - JOUR
T1 - Central dysmyelination reduces the temporal fidelity of synaptic transmission and the reliability of postsynaptic firing during high-frequency stimulation
AU - Kim, Sei Eun
AU - Turkington, Karl
AU - Kushmerick, Christopher
AU - Kim, Jun Hee
PY - 2013/10/1
Y1 - 2013/10/1
N2 - Auditory brain stem circuits rely on fast, precise, and reliable neurotransmission to process auditory information. To determine the fundamental role of myelination in auditory brain stem function, we examined the evoked auditory brain stem response (ABR) from the Long Evans shaker (LES) rat, which lacks myelin due to a genetic deletion of myelin basic protein. In control rats, the ABR evoked by a click consisted of five well-defined waves (denoted waves I-V). In LES rats, waves I, IV, and V were present, but waves II and III were undetectable, indicating disrupted function in the earliest stages of central nervous system auditory processing. In addition, the developmental shortening of the interval between waves I and IV that normally occurs in control rats was arrested and resulted in a significant increase in the central conduction time in LES rats. In brain stem slices, action potential transmission between the calyx of Held terminals and the medial nucleus of the trapezoid body (MNTB) neurons was delayed and less reliable in LES rats, although the resting potential, threshold, input resistance, and length of the axon initial segment of the postsynaptic MNTB neurons were normal. The amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) and the degree of synaptic depression during highfrequency stimulation were not different between LES rats and controls, but LES rats exhibited a marked slow component to the EPSC decay and a much higher rate of presynaptic failures. Together, these results indicate that loss of myelin disrupts brain stem auditory processing, increasing central conduction time and reducing the reliability of neurotransmission.
AB - Auditory brain stem circuits rely on fast, precise, and reliable neurotransmission to process auditory information. To determine the fundamental role of myelination in auditory brain stem function, we examined the evoked auditory brain stem response (ABR) from the Long Evans shaker (LES) rat, which lacks myelin due to a genetic deletion of myelin basic protein. In control rats, the ABR evoked by a click consisted of five well-defined waves (denoted waves I-V). In LES rats, waves I, IV, and V were present, but waves II and III were undetectable, indicating disrupted function in the earliest stages of central nervous system auditory processing. In addition, the developmental shortening of the interval between waves I and IV that normally occurs in control rats was arrested and resulted in a significant increase in the central conduction time in LES rats. In brain stem slices, action potential transmission between the calyx of Held terminals and the medial nucleus of the trapezoid body (MNTB) neurons was delayed and less reliable in LES rats, although the resting potential, threshold, input resistance, and length of the axon initial segment of the postsynaptic MNTB neurons were normal. The amplitude of glutamatergic excitatory postsynaptic currents (EPSCs) and the degree of synaptic depression during highfrequency stimulation were not different between LES rats and controls, but LES rats exhibited a marked slow component to the EPSC decay and a much higher rate of presynaptic failures. Together, these results indicate that loss of myelin disrupts brain stem auditory processing, increasing central conduction time and reducing the reliability of neurotransmission.
KW - ABR
KW - Auditory brain stem
KW - Auditory neuropathy
KW - Calyx of Held synapse
KW - MNTB principal neuron
KW - Myelin
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U2 - 10.1152/jn.00117.2013
DO - 10.1152/jn.00117.2013
M3 - Article
C2 - 23843435
AN - SCOPUS:84884936152
VL - 110
SP - 1621
EP - 1630
JO - Journal of Neurophysiology
JF - Journal of Neurophysiology
SN - 0022-3077
IS - 7
ER -