Excitotoxic effect of kainic acid on chicken cochlear afferent neurons Marlene Shero, Richard J. Salvi*, Lin Chen, Eri Hashino Center for Hearing and Deafness, State University of New York at Buffalo, 215 Parker Hall, Buffalo, NY 14214, USA Received 22 June 1998; received in revised form 21 September 1998; accepted 28 September 1998 Abstract The excitotoxic effects of kainic acid, a glutamate analog, on the auditory neurons in the chicken cochlea were assessed by light and transmission electron microscopy. Kainic acid was directly applied onto the round window of adult chickens and their cochleas were harvested 3 h after application. Transverse microscopic sections of the basilar papilla revealed swelling of afferent dendrites without any morphological changes in efferent endings. The regions of the basilar papilla damaged by kainic acid were localized in the apical 80% and primarily on the neural side where tall hair cells are located. The basal, abneural short hair cell region was devoid of damage. These results imply that glutamate is a primary neurotransmitter in chicken auditory afferent neurons that synapse on tall hair cells.  1998 Elsevier Science Ireland Ltd. All rights reserved Keywords: Kainic acid; Excitotoxicity; Glutamate; Cochlea; Afferent neuron; Chicken Kainic acid (KA) is an l-glutamate analog that mimics the endogenous excitatory amino acid, glutamate. Patholo- gical conditions, such as ischemia, cause an excessive release of glutamate inducing damage on glutamatergic neurons. The excitotoxic effects of glutamate have been investigated in a number of different neuronal models by using KA [3]. The effects of KA on the mammalian organ of Corti are well documented and it has been shown that KA selectively destroys the type I afferent dendrites which innervate the inner hair cells. However, KA has no effect on type II afferent fibers that contact outer hair cells [5,13,19]. An acute exposure of (±)-a-amino-3-hydroxy-5- methyl-4-isoxazole proprionic acid (AMPA), another gluta- mate analog, or KA resulted in complete elimination of the compound action potential (CAP) within 3 h, whereas the cochlear microphonic (CM), summating potential (SP), dis- tortion product otoacoustic emission (DPOAE) and endo- lymphatic potential (EP) remained unaffected [1,11,19]. The AMPA-induced damage to the afferent dendrites was protected by the administration of glutamate antagonists prior to AMPA treatment [12]. Collectively, the previous studies show that KA and AMPA can cause rapid and rever- sible damage to the type I afferent neurons. In contrast to the well documented excitotoxic effects of glutamate analogs in the mammalian organ of Corti, little is known about the role of glutamate in the avian peripheral auditory system. Although glutamate was shown to be released from isolated chick hair cells [6,7], it is not clear which hair cells release it and which neurons respond to it. In addition, no information is available about whether excess glutamate or its analogs causes excitotoxic effects similar to that seen in the mammalian organ of Corti. In the present study, we sought to determine if KA selectively damages the afferent nerve terminals in the chicken basilar papilla that mainly innervate the tall hair cells. A total of five White Leghorn chickens, 12–16 week old, were anesthetized with intramuscular injections of urethane (25%, 5.7 mg/kg) and ketamine (20–30 mg/kg), and artifi- cially ventilated (1.2–1.8 ml/minute) with humidified air. Body temperature was maintained at 41°C using a heating pad. The middle ear was opened and the round window exposed. A small drop of KA (65 mM, 100–200 ml) in bird Ringer’s solution (0.85 g NaCl, 0.042 g KCl, 0.025 g CaCl 2 in 100 ml H 2 O) was placed on the round window of the right ear for approximately 1 h and then wicked off. Neuroscience Letters 257 (1998) 81–84 0304-3940/98/$ - see front matter  1998 Elsevier Science Ireland Ltd. All rights reserved PII S0304-3940(98)00821-0 * Corresponding author. Tel.: +1 716 8292001; fax: +1 716 8292980; e-mail: salvi@acsu.buffalo.edu