Research paper Age-related changes in the response properties of cartwheel cells in rat dorsal cochlear nucleus Donald M. Caspary a,b, * , Larry F. Hughes b , Tracy A. Schatteman a , Jeremy G. Turner b a Department of Pharmacology, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629, United States b Department of Surgery, Southern Illinois University School of Medicine, P.O. Box 19629, Springfield, IL 62794-9629, United States Received 1 November 2005; received in revised form 1 March 2006; accepted 3 March 2006 Available online 27 April 2006 Abstract The fusiform cell and deep layers of the dorsal cochlear nucleus (DCN) show neurotransmitter and functional age-related changes suggestive of a downregulation of inhibitory efficacy onto DCN output neurons. Inhibitory circuits implicated in these changes include vertical and D-multipolar cells. Cartwheel cells comprise a large additional population of DCN inhibitory neurons. Cartwheel cells receive excitatory inputs from granule cell parallel fibers and provide a source of glycinergic inhibitory input onto apical den- drites of DCN fusiform cells. The present study compared the response properties from young and aged units meeting cartwheel-cell criteria in anesthetized rats. Single unit recordings from aged cartwheel cells revealed significantly higher thresholds, increased spon- taneous activity and significantly altered rate-level functions characterized by hyperexcitability at higher intensities. Aged cartwheel cells showed a significant reduction in off-set suppression. Collectively, these findings suggest a loss of tonic and perhaps response inhibition onto aged DCN cartwheel neurons. These changes likely reflect a compensatory downregulation of synaptic inhibition in response to a loss of excitatory drive from auditory and non-auditory excitatory inputs via granule cells. The impact of increased excitability of cartwheel cells on DCN output neurons is likely to be complex, influenced by loss of glycinergic release and/or subunit receptor changes which would only partially off-set age-related loss of inhibition onto the somata and basal dendrites of fusiform cells. Ó 2006 Elsevier B.V. All rights reserved. Keywords: Auditory; Aging; Cartwheel cells; Dorsal cochlear nucleus; Response properties 1. Introduction Age-related hearing loss (presbycusis) is a complex dis- order that results in a slow deterioration of peripheral audi- tory input to auditory regions of the brain (see Willott et al., 1991; Syka, 2002). With age-related hearing loss there is a loss of speech understanding, which can have an impact on the social and emotional health of the elderly (Thomas and Herbst, 1980; Weinstein and Ventry, 1982; Mulrow et al., 1990; Gordon-Salant and Fitzgibbons, 1993; Frisina and Frisina, 1997). Decline in the ability to discriminate speech, especially under noisy, complex acous- tic conditions, may reflect impaired processing of acoustic information within central auditory structures (Dubno et al., 1984; Moore et al., 1992; Fitzgibbons and Gordon- Salant, 1994; Schneider et al., 1994; Snell, 1997; Strouse et al., 1998; Tremblay et al., 2002, 2003; Ostroff et al., 2003). Functional and neurochemical studies in animal models suggest that sensory aging may involve compensa- tory inhibitory neurotransmitter changes within the central nervous system (Caspary et al., 1990, 2002, 2005; Schmole- sky et al., 2000; Mendelson and Ricketts, 2001; Leventhal et al., 2003). Thus, clinically observed age-related central 0378-5955/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.heares.2006.03.005 Abbreviations: DCN, dorsal cochlear nucleus; CN, cochlear nucleus; FBN, Fischer Brown Norway; HRP, horseradish peroxidase; TDT, Tuc- ker Davis Technologies; CF, characteristic frequency; PSTH, post-stim- ulus time histograms; RLF, rate-level function; ABR, auditory brainstem response; ANOVA, analysis of variance * Corresponding author. Tel.: +1 217 545 2195; fax: +1 217 545 0145. E-mail address: dcaspary@siumed.edu (D.M. Caspary). www.elsevier.com/locate/heares Hearing Research 216–217 (2006) 207–215 Hearing Research