Coding in Auditory Neurons: Effects of Amino Acids

PROJECT SUMMARY
Age-related hearing loss (ARHL) is a complex disorder affecting between 50-70% of the United States population
aged 65 or older. In public settings, seniors frequently have great difficulty understanding speech, which can
lead to withdrawal from social activities, depression and cognitive decline. All individuals and especially the
elderly can maintain speech understanding in difficult listening conditions by engaging attentional, cognitive and
mnemonic (top-down) resources to help disambiguate speech from a degraded ascending acoustic code.
Understanding the impact of aging on circuits that maintain speech understanding and the pharmacology of
cholinergic attentional systems in their modulation is at the core of the proposed studies.
Studies during the previous grant period identified differential age-related changes in nicotinic cholinergic
receptor (nAChR) subunit/subtypes in the medial geniculate body (MGB) and primary auditory cortex (AI). In
vitro aging studies detailed the pre- and postsynaptic function of nAChRs in thalamic circuits likely to underpin
attentional modulation of acoustic information. Unit recordings from awake rat auditory thalamus MGB also
showed age-related repetition-enhancement, as opposed to sensory adaptation, in response to
repeating/predictable temporally rich stimuli. This was posited to reflect increased use of corticofugal/higher-
order resources. Age-related enhanced coding of repeating modulated stimuli was reproduced in young animals
by simply degrading the temporal clarity of the sinusoidal amplitude modulated (SAM) stimuli. Corticothalamic
blockade of projections to MGB reversed predictive repetition-enhancement to a degree, but not completely. The
proposed Specific Aims will address questions raised by these prior studies and supported by preliminary data.
In vitro and in vivo approaches in rats will: SA1: Characterize the functional pharmacology and the impact of
aging on nAChR pharmacology in the central and dorsal nuclei of the inferior colliculus (CNIC, ENIC and DNIC).
SA2A: Determine single unit response properties of CNIC and DNIC units to temporally distinct and less
temporally distinct SAM stimuli presented in repeating/predictable or random sequences. SA2B: Determine the
impact of aging on the response properties of CNIC and DNIC units to repeating vs. randomly presented SAM
stimuli. SA3. Determine the impact of pontine mesencephalic tegmentum (PMT) release of acetylcholine on the
response properties of IC units to temporally distinct and temporally less distinct SAM stimuli presented in a
repeating or random sequences. Understanding the mechanisms involved in repetition enhancement/predictive
coding and identification of novel nAChR subtypes potentially resistant to aging will inform future behavioral and
pharmacotherapeutic approaches to improve speech understanding in the elderly.

Grant Number: 5U01DC000151-40
NIH Institute/Center: NIH
Principal Investigator: Donald Caspary