Premium
Reversible and irreversible damage to cochlear afferent neurons by kainic acid excitotoxicity
Author(s) -
Sun Hong,
Hashino Eri,
Ding DaLian,
Salvi Richard J.
Publication year - 2000
Publication title -
journal of comparative neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.855
H-Index - 209
eISSN - 1096-9861
pISSN - 0021-9967
DOI - 10.1002/1096-9861(20010205)430:2<172::aid-cne1023>3.0.co;2-w
Subject(s) - kainic acid , postsynaptic potential , cochlea , biology , excitotoxicity , spiral ganglion , hair cell , anatomy , neuron , afferent , neuroscience , glutamate receptor , programmed cell death , apoptosis , receptor , biochemistry
Kainic acid (KA) selectively damages afferent synapses that innervate, in chickens, mainly tall hair cells. To better understand the nature of KA‐induced excitotoxic damage to the cochlear afferent neurons, KA, at two different concentrations (0.3 or 5 mM), was injected directly into the inner ear of adult chickens. Pathologic changes in the afferent nerve ending and cell body were evaluated with light and transmission electron microscopy at various time points after KA application. The compound action potential (CAP) and cochlear microphonic (CM) potential were recorded to monitor the physiologic status of the afferent neurons and hair cells, respectively. Hair cell morphology and function were essentially normal after KA treatment. However, afferent synapses beneath tall hair cells were swollen within 30 minutes after KA at both low (KA‐L) and high (KA‐H) doses. In the KA‐L group, the swelling disappeared within 1 day and the morphology of the postsynaptic region returned to near normal condition. In the KA‐H group, by contrast, the vacant region beneath tall hair cells remained evident even 20 weeks after KA. The number of cochlear ganglion neurons in the KA‐H group decreased progressively from 1 to 8–20 weeks, whereas hair cells in the basilar papilla remained morphologically intact out to 20 weeks after KA. There was no significant change in neuron number in the KA‐L group. Temporal changes in the CAP amplitude paralleled the anatomic changes, although the CAP only partially recovered. These results suggest that KA induces partially reversible damage to cochlear afferent neurons with low KA concentration; above this level, KA triggers irreversible, progressive neurodegeneration. J. Comp. Neurol. 430:172–181, 2001. © 2001 Wiley‐Liss, Inc.