Jonathan A. N. Fisher, Ph.D
Laboratory of Sensory Neuroscience
The Rockefeller University
1230 York Avenue
New York, NY 10065
Contact: jfisher at rockefeller dot edu
I'm a research associate in the Laboratory of Sensory Neuroscience at The Rockefeller University. My background is in applied physics and optics, and I work on problems in molecular, cellular, and systems neuroscience. My current research is focused on the biophysics and neurophysiology of the auditory system. My research interests also include biomedical optics (particularly the development of new neuroimaging techniques) and auditory processing. My present work is funded by a Bristol-Myers Squibb Fellowship in the Basic Neurosciences and by a grant from the American Hearing Research Foundation (Fisher, PI).
Research Overview and Selected Publications
The neurophysiology and biophysics of hearing
Our sense organs represent the gateway between the physical world and our internal, abstract neural representation. Much of the precision, richness, as well as illusion with which we perceive the world can be explained by the biophysics of these sensors.
Hearing is a remarkable sense in that it allows us to detect, locate, and characterize complex sound sources at great distances, even if those sources are visually hidden or masked by the presence of other sounds. Human hearing is exquisitely sensitive over a vast range of sounds. We can hear faint sounds down to the level of thermal fluctuations in the ear, and our ability to discern subtle differences in tone allows us to distinguish human voices of nearly identical timbre. We additionally perceive sounds of vastly differing intensities on a similar scale, enabling us to clearly hear the distant strumming of nylon strings from a classical guitar playing in concert with a full orchestra.
These capabilities, which are largely lost in individuals with sensorineural hearing loss, arise from a dynamic interplay between sound and sensation in the inner ear: uniquely among our senses, the cochlea actively amplifies its own sound stimuli. Identifying the cellular and molecular components that give rise to this active process is the main biological focus of my current research.
J. A. N. Fisher, F. Nin, T. Reichenbach, R. Uthaiah, A. J. Hudspeth. 2012. The spatial pattern of cochlear amplification. Neuron 76(5): 989-997 [cover] Online
Cochlear traveling wave measured in vivo
This reconstruction from interferometric data depicts cochlear a traveling wave measured in vivo under control conditions (top panel) and after anoxia (bottom panel). The waves travel from the base of the cochlea, which is oriented to the left, and peak at the characteristic place for the stimulus frequency. Plotting the results on identical ordinate axes emphasizes the amplification associated with active, healthy hearing. Measured in the cochlea of a single chinchilla with sensitive hearing, the waves were elicited by a 9.4 kHz tone at 90 dB SPL. The data represent interferometric measurements at points on a Cartesian grid that spanned a 175 X 600 micron segment of the basilar membrane.
New Techniques for Neuroimaging
Neurons communicate electrically through changes in their membrane voltage that propagate along excitable membranes. At synapses, these electrical signals are relayed chemically by neurotransmitters. While fMRI has yielded a wealth of insights into in vivo neurological function, the signals are inherently metabolic in origin. A deeper understanding of the macroscopic electrical communication in the brain is dependent on the emergence of new imaging modalities.
Imaging individual action potentials from single nerve terminals
The fast all-or-nothing action potential is the fundamental unit of information flow in the nervous system. Recording action potentials in vivo typically requires the use of invasive electrodes. Using a voltage-sensitive membrane-bound dye and two-photon microscopy, we were able to record individual action potentials (in single trials) from single mammalian nerve terminals for the first time.
J. A. N. Fisher, J. R. Barchi, C. G. Welle, G-H. Kim, P. Kosterin, A. L. Obaid, A. G. Yodh, D. Contreras, B. M. Salzberg. 2008. Two-photon excitation of potentiometric probes enables optical recording of action potentials from individual mammalian nerve terminals in situ. Journal of Neurophysiology 99: 1545-1553. PDF
Multifocal 2-photon microscopy
Scanning-based imaging techniques suffer from low temporal resolution. One technique for speeding up acquisition is by multiplexing the scanning by using multiple scan beams. In this work, described in my dissertation, I developed a multifocal 2-photon microscope for in vivo imaging.
3D Endoscopic Imaging of Neural Activity in vivo
Optical imaging devices with small, implantable objective lenses enable an entirely new set of physiological experiment possibilities. From chronically-implanted imaging devices in awake, behaving animals to surface-penetrating hypodermic lenses, these devices have a unique niche in functional and molecular imaging. By implementing a small stepper motor to adjust a CCD detector position, we enabled 3D fluorescence imaging of neural electrical activity in vivo using a small diameter gradient-index (GRIN) lens as an objective. Results revealed large-scale differences in cortical processing in response to thalamic vs. nearby cortical electrical stimulation.
J. A. N. Fisher, E. F. Civillico, D. Contreras, A. G. Yodh. 2004. In vivo fluorescence microscopy of neuronal activity in three dimensions by use of voltage-sensitive dyes. Optics Letters 29(1): 71-73. PDF
New contrast agents for optical imaging
Functional and molecular fluorescence imaging offers new windows into examining complex biological systems from the whole-animal spatial scale down to sub-micron scale. For a variety of imaging modalities, and in particular for nonlinear optical microscopy (e.g. multi-photon excited fluorescence, second harmonic generation), new materials with custom electrical susceptibilities are crucial. In a collaboration with chemistry groups, we measured the nonlinear optical properties of novel compounds, in particular assessing their utility for 2-photon absorption applications. These materials, which offer large two-photon absorption cross-sections, are also useful for a variety of optical and electro-optic technologies including optical data storage, lithographic microfabrication, optical limiting devices, and medical photodynamic therapy.
J. A. N. Fisher, K. Susumu, M. Therien, A. G. Yodh. 2009. One- and two-photon absorption of highly conjugated multiporphyrin systems in the two-photon Soret transition region. Journal of Chemical Physics 130(13):134506 PDF
K. Susumu, J. A. N. Fisher, J. Zheng, D. N. Beratan, A. G. Yodh, M. J. Therien. 2011. Two-Photon Absorption Properties of Proquinoidal D-A-D and A-D-A Quadrupolar Chromophores. Journal of Physical Chemistry A Online