Coding in Auditory Neurons: Effects of Amino Acids
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Principal Investigator: Donald M. Caspary Organization: SOUTHERN ILLINOIS UNIVERSITY SCH OF MED Fiscal Year: 2024 Award: $559,289 Funding agency: National Institute on Deafness and Other Communication Disorders 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. Terms: <65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><> 65 years><ACh Receptors><Acetylcholine><Acetylcholine Receptors><Acoustics><Affect><Aged 65 and Over><Aging><Amino Acids><Anesthesia><Anesthesia procedures><Attention><Auditory><Auditory Cortex><Auditory area><Auditory system><Award><Behavioral><Binding><Brain><Brain Nervous System><Cell Body><Cell Communication and Signaling><Cell Nucleus><Cell Signaling><Cells><Cholinergic Receptors><Cholinoceptive Sites><Cholinoceptors><Code><Coding System><Cognition><Cognitive><Cognitive Disturbance><Cognitive Impairment><Cognitive decline><Cognitive function abnormal><Common Rat Strains><Complex><Data><Development><Differences between sexes><Differs between sexes><Disease><Disorder><Disturbance in cognition><Dorsal><Drug Design><Drug Targeting><Drugs><Elderly><Electrophysiology><Electrophysiology (science)><Encephalon><Exposure to><FISH Technic><FISH Technique><FISH analysis><FISH assay><Female><Fluorescence In Situ Hybridization><Fluorescent in Situ Hybridization><Future><Glutamates><Grant><Hearing><Impaired cognition><In Vitro><Individual><Industrialization><Inferior Colliculus><Intracellular Communication and Signaling><Knowledge><L-Glutamate><Location><Medial geniculate body><Mediating><Medication><Mental Depression><Modeling><Molecular Interaction><Nerve Cells><Nerve Transmitter Substances><Nerve Unit><Neural Cell><Neurocyte><Neurons><Neurophysiology / Electrophysiology><Neurotransmitters><Nicotinic Acetylcholine Receptors><Nicotinic Receptors><Norway Rats><Nucleus><Older Population><Pharmaceutical Preparations><Pharmacology><Pons><Pons Cerebelli><Pons Varolii><Pontine><Pontine structure><Population><Posterior Quadrigeminal Body><Presbyacusis><Presbycusis><Property><Rat><Rats Mammals><Rattus><Rattus norvegicus><Receptor Activation><Receptor Protein><Research Resources><Resistance><Resources><Sensory><Sex Differences><Sexual differences><Signal Transduction><Signal Transduction Systems><Signaling><Slice><Social isolation><Speech><Stimulus><Structure><System><Tegmentum Mesencephali><Thalamic structure><Thalamus><Transcript><United States><Withdrawal><above age 65><acetylcholine receptor agonist><adult youth><advanced age><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age associated><age associated alterations><age associated changes><age associated effects><age associated hearing loss><age correlated><age correlated alterations><age correlated changes><age dependent><age dependent alterations><age dependent changes><age effect><age induced hearing loss><age linked><age of 65 years onward><age related><age related alterations><age related changes><age related decline in hearing><age related effects><age related hearing deficits><age related hearing impairment><age related hearing loss><age specific><age specific alterations><age specific changes><aged><aged 65 and greater><aged 65+><aged ≥65><aging associated hearing loss><aging effect><aging induced hearing loss><aging related decline in hearing><aging related hearing deficits><aging related hearing impairment><aging related hearing loss><alterations with age><aminoacid><antagonism><antagonist><attention modulation><attentional modulation><auditory pathway><auditory thalamus><awake><biological signal transduction><cell type><changes with age><cholinergic><cognitive dysfunction><cognitive loss><depression><design><designing><developmental><drug development><drug/agent><electrophysiological><geriatric><glutamatergic><human old age (65+)><impact of age><improved><in vivo><influence of age><information processing><juvenile animal><male><neuronal><novel><old age><older groups><older individuals><older person><optogenetics><over 65 years><patch clamp><pharmacologic><postsynaptic><preference><presynaptic><radioligand><receptor><receptor function><resistant><response><senior citizen><sex based differences><sex-dependent differences><sex-related differences><sex-specific differences><social><synapse function><synaptic function><tegmentum><thalamic><young adult><young adulthood><young animal><≥65 years>