title: Excitability of auditory brainstem neurons, in vivo, is increased by cyclic-AMP.
abstract: Physiological control of auditory neural responses is critical for accurate representation of acoustic information, such as sound source localization and speech perception. Central auditory neural responses are almost certainly regulated by a range of mechanisms, including second messenger systems, such as the cAMP pathway. An increase in spontaneous neural discharge is known to accompany cochlear insults. Here we report that an increase in spontaneous as well as tone-evoked discharge can also be induced by pressure application of forskolin, a pharmacological agent that elevates intracellular cAMP level by activating adenyl cyclase. The forskolin induced increase in superior olivary complex (SOC) brainstem neurons is specific, dose-dependent, and reversible, whereas application of artificial cerebrospinal fluid (aCSF, the vehicle) does not alter activity. Forskolin-application also has a relatively greater effect on spontaneous activity compared to tone evoked responses. Blockade of the hyperpolarization-activated current, Ih, by ZD7288, consistently reversed the effects of forskolin. Based on these findings, we propose that the second messenger, cAMP, can significantly modulate neural excitability and spontaneous discharge in SOC neurons, principally by shifting the activation of Ih channels.
authors.affiliation: Department of Otolaryngology, School of Medicine, Wayne State University, Detroit, MI 48201, USA. ashaikh@med.wayne.edu
authors.forename: Aasef G
authors.initials: AG
authors.lastname: Shaikh
authors.forename: Paul G
authors.initials: PG
authors.lastname: Finlayson
mesh_terms: D000161:Acoustic Stimulation; D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001307:Auditory Perception / Q000187:drug effects / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009847:Olivary Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D018690:Excitatory Amino Acid Agonists; D007473:Ion Channels; D011743:Pyrimidines; C082246:ICI D2788; D005576:Colforsin; D018698:Glutamic Acid; D000242:Cyclic AMP; D000262:Adenylyl Cyclases