Elias Aizenman, PhD, professor of neurobiology,and Thanos Tzounopoulos, PhD, Endowed Professor and Vice Chair of Research in the Department of Otoralyngology, have received a $1.24 million grant from the National Science Foundation (NSF) to study a previously unknown link between the metal zinc and control of auditory processing in the cerebral cortex. Findings from this project are expected to advance understanding about mechanisms of adaptations of sound processing. For instance, the findings could provide insight into how the brain dampens its responses to constant background noise or repetitive loud sounds. Overall, the project is designed to create a new framework for approaching and interpreting the role of the auditory system in the processing of sound.

An Israeli arm of the study, headed by Michal Hershfinkel, PhD, of Ben-Gurion University of the Negev, is funded by the U.S.-Israel Binational Science Foundation (BSF). Aizenman and Hershfinkel have previously collaborated on BSF-funded studies of how neurons use zinc as a signaling molecule. Tzounopoulos  is an expert on zinc neurobiology and on auditory processing.

“We have shown that sound exposure evokes zinc release from the synaptic vesicles," Tzounopoulos says. "Once zinc is released in a sound-dependent manner, it modulates the magnitude of the sound-evoked response of auditory cortical neurons.”

Joint preliminary studies by the three investigators began to reveal clues about how zinc modulates sound processing and adaptation to sound. They determined that changes in the auditory environment rapidly modulate the levels of the proteins that regulate zinc levels in the auditory cerebral cortex, suggesting a role of zinc in adaptive hearing processing.

With the help of the NSF-BSF partnership grant, the team is going further to analyze neuronal zinc and its effects on the auditory system. The team hopes to identify the pathways that are activated by sound-evoked zinc release, and understand how these pathways modulate sound processing. By revealing the basic roles of zinc in the synapses, the investigators may begin to understand how the brain discriminates between frequency or level of sound.

“The previously-funded BSF projects allowed the establishment of a collaborative and synergistic experimental setup between our research groups,” Hershfinkel says. “These studies, which were based on the mutual interests of our laboratories, enabled us to interact and conceive novel hypotheses that were based on the distinct viewpoints and strengths of each of the principal investigators.” Their past research has already led to 11 joint papers.

“These grants have helped us work together in ways that have opened new avenues for our research," Aizenman says. The current NSF/BSF project will establish a US-Israel student exchange program, as well as target underserved student populations both in Israel and the United States.  The students will be trained in  problem-solving at behavioral, neural and molecular levels of analysis.

"We are delighted that the ongoing collaboration among the three laboratories has significantly enhanced the training opportunities of our students and postdocs,” Aizenman says. “We are making new discoveries, and at the same time, we are training the next generation who will make their own discoveries.”  The investigators say broad dissemination of the work will be made possible by active engagement with the International Society for Zinc Biology Biology (ISZB.org), where both Aizenman and Hershfinkel have served as past presidents..

--Adapted from a BSF profile