DPOAE assessment of cochlear function in tinnitus subjects with normal hearing sensitivity

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2009.Cataloged from PDF version of thesis.Includes bibliographical references (p. 48-50).Tinnitus, the perception of sound in the absence of an external acoustic source, disrupts the daily life of 1 out of every 200 adults, yet its physiological basis remains largely a mystery. While tinnitus and hearing loss (i.e., elevated pure tone thresholds) commonly co-occur, many people without hearing loss experience tinnitus, raising the question of whether cochlear pathology is always a prerequisite for this percept. This study used distortion product otoacoustic emissions (DPOAEs) to evaluate the cochlear amplifier of 13 tinnitus subjects and 13 non-tinnitus subjects (matched by age, sex, and audiogram) across a broad range of frequencies and intensities. DPOAE magnitudes were measured for at least 52 frequencies (500 Hz <f2 5 8 kHz, with f2ff=1.2) and nine intensities (20 dB < L2 5 60 dB, with L, = 39 + 0.4L2) in each ear. Further, this study only considered ears with normal audiograms and unremarkable history so that any abnormal findings could not be attributed large-scale hair cell damage within the cochlea. Consistent differences in the shape of the DP-gram (DPOAE magnitude as a function of presentation frequency, f2) were found in tinnitus subjects. A quantitative method for assessing DP-gram shape was developed, and statistical analyses were performed to determine whether tinnitus or other patient characteristics correlated with the abnormal DP-gram shape. The data collected in this study suggest peripheral auditory malfunction in tinnitus subjects with normal audiograms.by Leah C. Acker.S.M

Noninvasive optical inhibition with a red-shifted microbial rhodopsin

Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium) salinarum (strain Shark) and engineered to result in red light–induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice. We also demonstrate that Jaws can noninvasively mediate transcranial optical inhibition of neurons deep in the brains of awake mice. The noninvasive optogenetic inhibition opened up by Jaws enables a variety of important neuroscience experiments and offers a powerful general-use chloride pump for basic and applied neuroscience.McGovern Institute for Brain Research at MIT (Razin Fellowship)United States. Defense Advanced Research Projects Agency. Living Foundries Program (HR0011-12-C-0068)Harvard-MIT Joint Research Grants Program in Basic NeuroscienceHuman Frontier Science Program (Strasbourg, France)Institution of Engineering and Technology (A. F. Harvey Prize)McGovern Institute for Brain Research at MIT. Neurotechnology (MINT) ProgramNew York Stem Cell Foundation (Robertson Investigator Award)National Institutes of Health (U.S.) (New Innovator Award 1DP2OD002002)National Institute of General Medical Sciences (U.S.) (EUREKA Award 1R01NS075421)National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1RC1MH088182)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Science Foundation (U.S.) (Career Award CBET 1053233)National Science Foundation (U.S.) (Grant EFRI0835878)National Science Foundation (U.S.) (Grant DMS0848804)Society for Neuroscience (Research Award for Innovation in Neuroscience)Wallace H. Coulter FoundationNational Institutes of Health (U.S.) (RO1 MH091220-01)Whitehall FoundationEsther A. & Joseph Klingenstein Fund, Inc.JPB FoundationPIIF FundingNational Institute of Mental Health (U.S.) (R01-MH102441-01)National Institutes of Health (U.S.) (DP2-OD-017366-01)Massachusetts Institute of Technology. Simons Center for the Social Brai

Optogenetic disruption of memory-drive, oculomotor behavior in the non-human primate

Thesis: Ph. D., Harvard-MIT Program in Health Sciences and Technology, 2014.Cataloged from PDF version of thesis.Includes bibliographical references (pages 130-139).Pharmacological inactivation studies have shown that the frontal eye field (FEF) is critical for executing saccades to remembered locations. FEF neurons increase their firing rate during the three epochs of the memory-guided saccade task: visual stimulus presentation, the delay interval, and motor preparation. It is unclear, though, whether FEF activity during each epoch is necessary for memory-guided saccade execution. To address this question, techniques for millisecond-precise optical inactivation of the primate brain were invented. A red-shifted halorhodopsin (Jaws) and a novel large-volume tissue illuminator were used in two rhesus macaques to inactivate part of the FEF at different times during the memory-guided saccade task. Neuronal recordings showed that the inactivated tissue volume (i.e., the volume where the firing rate of >80% of neurons decreased by >80%) spanned several cubic millimeters, which is consistent with histological findings. When the target was in the inactivated receptive field, error rates (i.e., failures to execute memory-guided saccades to the proper target location) increased in both monkeys with inactivation during either the target, delay, or motor period. This implies that FEF neuronal activity contributes to performance throughout the memory-guided saccade task.by Leah C. Acker.Ph. D

An Open Resource for Non-human Primate Optogenetics.

Optogenetics has revolutionized neuroscience in small laboratory animals, but its effect on animal models more closely related to humans, such as non-human primates (NHPs), has been mixed. To make evidence-based decisions in primate optogenetics, the scientific community would benefit from a centralized database listing all attempts, successful and unsuccessful, of using optogenetics in the primate brain. We contacted members of the community to ask for their contributions to an open science initiative. As of this writing, 45 laboratories around the world contributed more than 1,000 injection experiments, including precise details regarding their methods and outcomes. Of those entries, more than half had not been published. The resource is free for everyone to consult and contribute to on the Open Science Framework website. Here we review some of the insights from this initial release of the database and discuss methodological considerations to improve the success of optogenetic experiments in NHPs

An Open Resource for Non-human Primate Optogenetics

Optogenetics has revolutionized neuroscience in small laboratory animals, but its effect on animal models more closely related to humans, such as non-human primates (NHPs), has been mixed. To make evidence-based decisions in primate optogenetics, the scientific community would benefit from a centralized database listing all attempts, successful and unsuccessful, of using optogenetics in the primate brain. We contacted members of the community to ask for their contributions to an open science initiative. As of this writing, 45 laboratories around the world contributed more than 1,000 injection experiments, including precise details regarding their methods and outcomes. Of those entries, more than half had not been published. The resource is free for everyone to consult and contribute to on the Open Science Framework website. Here we review some of the insights from this initial release of the database and discuss methodological considerations to improve the success of optogenetic experiments in NHPs.status: publishe