Development of glutamate and NMDA sensitivity of neurons within the cochlear nuclear complex of kittens.
1. The effects of glutamate, N-methyl-D-aspartate (NMDA), and NMDA receptor antagonists, D-alpha-aminoadipate (D alpha AA) and 2-amino-5-phosphonovalerate (APV), microionophoretically applied onto neurons in the caudal divisions (posteroventral and dorsal subnuclei) of the cochlear nuclear complex (CN), were investigated during postnatal development in kittens with the use of extracellular techniques. From birth through postnatal day 7, microionophoretically applied glutamate elevated the acoustically evoked discharge rates of nearly 80% of neurons studied. Although fewer neurons were studied with the use of NMDA, approximately 65% of these responded to this glutamatergic agonist, and no developmental changes in the percentage of responsive neurons were observed. The actions of NMDA antagonists were studied in a relatively small number of neurons, and results support the supposition that glutamate, or a glutamate-like substance, acts as a CN neurotransmitter throughout postnatal life. 2. Approximately 64% of CN neurons encountered among neonatal animals were unresponsive to acoustic stimulation, even at the highest output levels available (> 120 dB SPL). That percentage declined monotonically during the next three postnatal days, such that approximately 23% of neurons encountered were unresponsive to acoustic stimulation on the third day. Essentially all encountered neurons were responsive to acoustic stimulation by the middle of the second postnatal week. Under conditions of simultaneous glutamate and acoustic stimulation, neurons in this general class of "acoustically unresponsive" neurons segregated into two groups. Glutamate increased spontaneous discharge rate in 45% of the neurons studied, however, these units remained acoustically unresponsive during combined sound and excitatory amino acid stimulation (group A1). In the second group (A2), 55% of the neurons that were acoustically unresponsive under control (sound alone) conditions responded to the acoustic component of the combined acoustic and glutamate stimulation (the experimental condition) in a frequency-dependent manner. A2 neurons exhibited temporal firing patterns characteristic of acoustically responsive neurons of corresponding age, suggesting that these neurons are functionally connected to the auditory periphery, whereas A1 neurons are not. 3. Dose-response curves were either sigmoidal or linear over the range that measurements were made, and maximum discharge rates evoked by high doses of glutamate in the youngest animals studied tended to be lower than those produced by acoustic stimulation alone in older animals. These results suggest that intrinsic properties contribute to the mechanism(s) that limits neuronal responsiveness. Average dose-response curve slopes were higher for neurons recorded from older animals, also indicating that intrinsic properties regulating dynamic response range are acquired postnatally in the kitten CN.(ABSTRACT TRUNCATED AT 400 WORDS)
Walsh
E J
EJ
Boys Town National Research Hospital, Omaha, Nebraska.
McGee
J
J
Fitzakerley
J L
JL
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D015074:2-Aminoadipic Acid / Q000494:pharmacology; D000161:Acoustic Stimulation; D000367:Age Factors; D000818:Animals; D001931:Brain Mapping; D002415:Cats; D003056:Cochlear Nerve / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D005971:Glutamates; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D015074:2-Aminoadipic Acid; D018698:Glutamic Acid; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate