Learning and memory are absolutely essential to hearing. In their absence, comprehension would be impossible because no auditory information could be acquired or stored, and the recognition of previously heard sounds would be impossible. The long-term objectives of this research project are to discover the neural mechanisms that enable sounds to acquire meaning. The primary auditory cortex (A1) has been identified as a site for the acquisition and storage of auditory information. In general, encoding of behaviorally relevant sounds is strengthened as part of an overall functional remodeling of acoustic representation. For example, when a tone becomes a signal for rewarding or aversive stimuli, frequency tuning shifts toward or to the signal frequency, strengthening its encoding while weakening that of other frequencies. Tuning shifts can increase the area of signal representation in A1, and the amount of gain is directly proportional to both the cue's level of acquired importance and its memory strength. Such representational plasticity (RP) appears to be a substrate of auditory memory because it has the same attributes as memory itself. Engagement of mAChR's in A1 directly or by pairing tone with stimulation of the cholinergic nucleus basalis (NBstm) is sufficient to (a) produce RP, (b) actually implant specific behavioral auditory memory, and (c) increase neural synchrony (NSync). Further, increased synchrony predicts both RP in A1 and auditory memory. Thus, sounds may gain meaning via increased neural synchrony, which gives them greater effectiveness in communicating with target structures and strengthening their own representations.
The specific aims of this project are to determine if increasing NSynch (gamma band oscillations and unit co-variances) during signal presentation can strengthen and increase the specificity of auditory memory, and/or enhance RP. Rats will be trained in auditory fear and reward tasks while a signal tone's induced neural synchronization is boosted via increasing loudness or brief concurrent NBstm. Studies will determine if increasing NSync can enhance memory strength and specificity, using custom designed training protocols that produce a modest level of RP and memory. If these experiments uncover neural synchrony as a mechanism sufficient to strengthen and/or produce specific auditory memory, then this project will have opened a pathway for remediation of auditory comprehension disorders.

Public Health Relevance

Many problems in hearing are auditory processing disorders that impair the ability to properly grasp the meaning of language and other sounds. The goal of this research project is to discover the brain mechanisms that provide for comprehension of sound. Once these are known, effective treatments can be designed and used to treat those disorders.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01DC002938-16A1
Application #
8754728
Study Section
Auditory System Study Section (AUD)
Program Officer
Platt, Christopher
Project Start
Project End
Budget Start
Budget End
Support Year
16
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
City
Irvine
State
CA
Country
United States
Zip Code
92697
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Bieszczad, Kasia M; Kant, Ritu; Constantinescu, Cristian C et al. (2012) Nicotinic acetylcholine receptors in rat forebrain that bind ýýýýýF-nifene: relating PET imaging, autoradiography, and behavior. Synapse 66:418-34
Headley, Drew B; Weinberger, Norman M (2011) Gamma-band activation predicts both associative memory and cortical plasticity. J Neurosci 31:12748-58
Miasnikov, Alexandre A; Chen, Jemmy C; Weinberger, Norman M (2011) Consolidation and long-term retention of an implanted behavioral memory. Neurobiol Learn Mem 95:286-95
Weinberger, Norman M (2011) The medial geniculate, not the amygdala, as the root of auditory fear conditioning. Hear Res 274:61-74
Weinberger, Norman M; Miasnikov, Alexandre A; Chen, Jemmy C (2009) Sensory memory consolidation observed: increased specificity of detail over days. Neurobiol Learn Mem 91:273-86
Miasnikov, Alexandre A; Chen, Jemmy C; Weinberger, Norman M (2009) Behavioral memory induced by stimulation of the nucleus basalis: effects of contingency reversal. Neurobiol Learn Mem 91:298-309
Hui, Gabriel K; Wong, Kwan L; Chavez, Candice M et al. (2009) Conditioned tone control of brain reward behavior produces highly specific representational gain in the primary auditory cortex. Neurobiol Learn Mem 92:27-34
Miasnikov, Alexandre A; Chen, Jemmy C; Gross, Nataliya et al. (2008) Motivationally neutral stimulation of the nucleus basalis induces specific behavioral memory. Neurobiol Learn Mem 90:125-37
Miasnikov, Alexandre A; Chen, Jemmy C; Weinberger, Norman M (2008) Specific auditory memory induced by nucleus basalis stimulation depends on intrinsic acetylcholine. Neurobiol Learn Mem 90:443-54

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