Auditory comprehension, as well as auditory analysis, is essential for hearing. The comprehension of sound requires enduring auditory memory, i.e., the storage of the learned meanings of sounds. The rich and complex domain of auditory memory is enabled by the plasticity of the auditory cortex. For example, learning is accompanied by shifts of frequency tuning to emphasize sounds that become behaviorally important, as during associative learning. Although the fact of learning-induced cortical plasticity is now well-established, it alone cannot provide either an adequate understanding of the neural bases of auditory memory or the effective application of basic knowledge to clinical problems in hearing and communication. It is essential to determine the memory functions of cortical plasticity. The goals of this research project are to determine the memory functions of learning-induced cortical plasticity and the role of the cholinergic nucleus basalis as a mechanism mediating those functions. We hypothesize that three main functions of associative auditory plasticity are to enhance auditory memories by (1) making them stronger, (2) preserving their acoustic details and (3) promoting their flexible use to solve new auditory problems. To determine the functions of plasticity, it is necessary to control plasticity. We have already developed two ways to control plasticity: (a) indirectly by guiding learning strategies, (b) directly by stimulating the nucleus basalis. To test these hypotheses and reveal mnemonic functions of associative plasticity we will train rats with microelectrodes chronically implanted in their primary auditory cortex (A1), to bar-press for water in the presence of a tone. We will track the development of behavior and plasticity, and obtain complete functional maps of A1 in a subset of animals, by obtaining repeated profiles of neuronal discharge and local field potential responses to a broad range of pure tone frequency-level combinations. Post-training tests will assess memory strength, memory for details of acoustic experience and the ability to learn an auditory-cued avoidance task compared to appropriate control groups. If the nucleus basalis (NB) can meditate memory functions of A1, then pairing a tone with NB stimulation to induce A1 plasticity and auditory memory should increase the level of memory strength, retention of acoustic details and facilitate avoidance learning. The findings have direct translational implications for the design and implementation of therapeutic interventions, including remediation of phonological processing deficits in children and learning to comprehend speech following cochlear implantation. The optimal design of remediation training will directly benefit from promoting the desired type of specific cortical plasticity (assessed by scalp recordings or functional imaging) that can be custom-designed for each patient to promote strong, specific and flexible auditory memory.

Public Health Relevance

Auditory comprehension, as well as auditory analysis, is essential for hearing as it enables the recognition of all sounds including speech. The results of this project will significantly increase our understanding of how the brain acquires, represents, stores and utilizes auditory experience. The findings will be directly relevant to the design and implementation of therapeutic interventions, to enable and improve general auditory and speech comprehension.

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC010013-04
Application #
8302164
Study Section
Auditory System Study Section (AUD)
Program Officer
Platt, Christopher
Project Start
2009-09-18
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$295,947
Indirect Cost
$92,304
Name
University of California Irvine
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
046705849
City
Irvine
State
CA
Country
United States
Zip Code
92697
Bieszczad, K M; Miasnikov, A A; Weinberger, N M (2013) Remodeling sensory cortical maps implants specific behavioral memory. Neuroscience 246:40-51
Bieszczad, Kasia M; Weinberger, Norman M (2012) Extinction reveals that primary sensory cortex predicts reinforcement outcome. Eur J Neurosci 35:598-613
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
Weinberger, Norman M (2011) The medial geniculate, not the amygdala, as the root of auditory fear conditioning. Hear Res 274:61-74
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
Bieszczad, Kasia M; Weinberger, Norman M (2010) Remodeling the cortex in memory: Increased use of a learning strategy increases the representational area of relevant acoustic cues. Neurobiol Learn Mem 94:127-44