Synaptic regeneration and functional recovery after excitotoxic injury in the guinea pig cochlea.
Cochlear ischemia and acoustic trauma result in an immediate hearing loss accompanied by the complete disruption of the terminal dendrites of primary auditory neurons postsynaptic to the sensory inner hair cells (IHCs). This synaptic uncoupling, due to an acute glutamate (IHC neurotransmitter) excitotoxicity process, can be mimicked by glutamate agonists. Thus, we have followed over a 5-day period the responses of guinea-pig cochleas to a local application of 200 microM AMPA. This application immediately results in a destruction of all postsynaptic endings of the auditory nerve, resulting in a total loss of cochlear potentials. Twenty-four hours after this excitotoxic injury, the inner hair cells were contacted by repaired postsynaptic dendrites and the cochlear potential had partially recovered. This process of neo-synaptogenesis was completed and the potentials were fully restored at 5 days post exposure. As shown by in situ hybridization, an up-regulation of NMDA and metabotropic glutamate receptors in the primary auditory neurons occurred during this process of recovery. This process of neo-synaptogenesis and functional recovery probably accounts for restoring hearing after temporary losses due to excitotoxic-related pathologies.
Puel
J L
JL
INSERM U. 254, Université de Montpellier-I, France.
Saffiedine
S
S
Gervais d'Aldin
C
C
Eybalin
M
M
Pujol
R
R
D000818:Animals; D003051:Cochlea / Q000187:drug effects / Q000293:injuries*; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D006199:Hair Cells, Auditory, Inner / Q000502:physiology; D008297:Male; D009416:Nerve Regeneration; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D000159:Vestibulocochlear Nerve / Q000166:cytology / Q000502:physiology*; D061285:Vestibulocochlear Nerve Injuries; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid