Venkatesh Murthy, PhD

Professor

Department of Molecular and Cellular Biology, Faculty of Arts and Sciences

Synaptic plasticity; neuronal circuits and adaptation in the rodent olfactory system

Study synaptic plasticity in the rodent brain to understand compensation mechanisms, how neurons maintain stable function during perturbations; understand the function of neuronal circuits in the rodent olfactory system and how they mediate the sense of smell.

Image

Commercial Opportunities

The understanding of how brain circuitry works as well as how it is coupled to blood flow will yield insights into what goes wrong in neurodegenerative diseases, the aging brain, and olfactory disorders. Similarly, the studies of synapses and synaptic plasticity will aid in the understanding of nerve damage. The spH mice can be crossed with mouse mutants that model specific brain disorders, affording a convenient way to investigate synaptic dysfunction. These insights into the nervous system could be applied to the future development of small molecules and other therapeutics to treat such diseases and conditions.

The nanowire arrays that Murthy and colleagues used for neurons could be applied to many other cell types, particularly in studies that require spatial resolution. The arrays could also be utilized to deliver biomolecules and reagents to cells, rather than as a monitoring device. This would be an efficient method to deliver several molecules at once to a given cell. Furthermore, new knowledge of the circuitry of the brain could be applied to advance computer technology.

Current Research Interests
  • Investigate mechanisms related to synaptic plasticity, particularly inhibitory synapses and homeostatic synaptic plasticity.
  • Determine how the olfactory system represents and processes odor information.
  • Reveal the logic behind synaptic circuits in the early olfactory system.
  • Ascertain how circuits and processing in the olfactory system are affected by odor experience and different brain states.
Tools and Assays

SpH mouse: A transgenic mouse line that expresses the pH-sensitive fluorescent protein synaptopHluorin, which permits in vivo imaging of presynaptic neurotransmitter release in specific classes of neurons. The spH mice can be crossed with mouse mutants that model specific brain disorders, affording a convenient way to investigate synaptic dysfunction.

OMP-ChR2 mice: transgenic mice that express a light-activated protein called Channelrhodopsin-2 in the olfactory sensory neurons, which allows quantitative control of sensory stimuli much more easily than odors themselves. These mice, which effectively "smell" light, have wide application in neuroscience – from studies of sensory coding to behavioral decision making.

2D Semiconductor nanowire transistor arrays: A nano-device that allows the study of live and acute brain slices by sensing action potentials, presynaptic firing and postsynaptic depolarization---all in sub-millisecond resolution as a neuron fires. In addition, the arrays allow the identification of neuronal regions and multiplex mapping in high spatial resolution. This technology could be applied to many other cell types, particularly in studies that require spatial resolution. The arrays could also be utilized to deliver biomolecules and reagents to cells, rather than as a monitoring device. This would be an efficient method to deliver several molecules at once to a given cell.

Research Expertise

The Murthy laboratory focuses on understanding how neural circuits process information and adapt to changing circumstances. They have elucidated the function of serotonin in the olfactory system, showing that serotonin gates the olfactory signal at individual olfactory glomeruli. Recent work by the group has led to the highest resolution odor map of the olfactory bulb to date, revealing that glomeruli less than 1 mm apart tend to have similar odor spectra, yet those immediately adjacent do not. This is the first study to systematically observe how the spacing of glomeruli relates to odor responses. Another research from the lab has shown that astrocyte senses presynaptic glutamate to regulate capillary dynamics when a given glomerulus is activated by a specific odor. This enabled further insight into how synaptic activity is coupled to astrocytes and blood flow.

The Murthy laboratory has developed many novel technologies and groundbreaking methods including the SpH mouse, a mouse line expresses the pH-sensitive fluorescent protein synaptopHluorin, which permits in vivo imaging of presynaptic neurotransmitter release in specific classes of neurons. Using genetically-engineered mice such as these, researchers are able to obtain precise and specific responses to sensory inputs, which can be visualized using advanced imaging techniques such as multiphoton laser scanning microscopy. The laboratory has also engineered mice expressing a light-activated protein called Channelrhodopsin-2 in the olfactory sensory neurons, which allows quantitative control of sensory stimuli much more easily than odors themselves. These mice, which effectively "smell" light, have wide application in neuroscience – from studies of sensory coding to behavioral decision making.

Technologies developed by the Murthy laboratory have advanced the field of monitoring neuronal networks. In collaboration with the Lieber laboratory, the scientists have developed semiconductor nanowire transistor arrays to study acute brain slices by sensing action potentials, presynaptic firing and postsynaptic depolarization, all in sub-millisecond resolution as a neuron fires. In addition, the nanowire arrays allow the identification of neuronal regions and multiplex mapping in high spatial resolution. Such combination of high temporal and spatial resolutions has never been accomplished before in the study of neuronal circuits and will no doubt reveal novel insights into brain function.