Noga Vardi, Ph.D.
1971-74 B.Sc. Hebrew University (Biology)
1975-81 Ph.D. Cornell University
Research Professor, University of Pennsylvania
Perception is an incredibly abstract and complicated brain function, which enables us to see the world through the filters of the sensory systems. Sensory neurons transduce physical signals (light, sound waves, molecules in the air) into electrical signals, and these are communicated between neurons. It is the ensemble of these neuronsí activity that is interpreted as a familiar face, a pleasant music, an obnoxious smell, etc.. Neurons communicate by a variety of cellular and molecular mechanisms whose principals and details Neuroscience is seeking.
I am interested in deciphering some of these principal mechanisms, and I use the visual retina as a model system. I address questions concerning the precise connections between neurons, both at the morphological and molecular levels. By knowing which chemicals are released from a cell, and which receptors receive a particular chemical, one can figure out which information is being communicated.
The retina is used as a model system for signal processing because it has several advantages over centers in the brain. First, the input is well defined: it is the pattern of light and dark "dots" that falls on the retina. Second, the output, which is carried out of the retina by ganglion cells, has been thoroughly studied. Third, the anatomy of the retinal is well studies both on the light and electron microscopic levels. The knowledge is so detailed that the number of synapses between specific cell type is known. Finally, the questions regarding signal processing are well defined: we know that photoreceptor (through retinal circuits) transfer information to ganglion cells under a wide range of luminances, and they do it very reliably! We know that to signal reliably, the retina has to employ gain control and noise removal mechanisms. The key question is: what is the molecular basis of these principal mechanism? Figuring out the chemical architecture of the circuit will decipher this question.
The Vardi Lab (2013)
Anuradha Dhingra (Ph.D)
Hari S Ramakrishnan (Ph.D)
Sergei Nikonov (Ph.D)
Previous students and postdocs:
Tian Li Wang - Currently at John Hopkins University
Katsuko Morigiwa - Currently at Osaka Bioscience Institute
Lingli Zhang - Currently at the University of Pennsylvania
Ying Xu - Currently at Jinan University
Pyroja Sulaiman - Maternity leave
Peter Auerbach (Emergency Doctor)
Tehila Bar-Yehuda (Entrepreneur)
From Left to right:
Ying Xu: Former Research Associate
Pyroja Sulaiman: Former Post doc
Marie Fina: Research Specialist
|Schematic to illustrate information transfer in the first visual synapse. Rod photoreceptors contact a single type of second order neuron: the rod bipolar cell. Cone photoreceptors contact 10 types of second order neurons which are divided into two classes: the ON and the OFF cone bipolar cells. ON cone bipolar cells and rod bipolar cells depolarize to light, while OFF cone bipolar cells hyperpolarize to light following the same polarity of photoreceptors. This happens because glutamate has two modes of action: using the conventional AMPA/kainate receptor, it depolarizes the OFF bipolar cells; and using the metabotropic glutamate receptor mGluR6, it hyperpolarizes ON bipolar cells.|
Immunocytochemistry, dye injection, electron microscopy, molecular biology, physiology, recording from oocytes, and ERG.
A transgenic mouse with green flourescent ON bipolar cells
To study mGluR6 cascade in ON bipolar cells we produced a mouse that expressed EGFP under the control of mGluR6 promoter.
Organization of receptors in the cone synaptic complex.
Localization of Cl- cotransporters
Chloride cotransporters contribute greatly to maintain certain chloride concentrations in neurons. One class of these transporters (Na-K-Cl) normally accumulates chloride by using the Na+ gradient, and another class (K-Cl) extrudes chloride by using the K+ gradient. Chloride concentration is extremely important because it determines the Ecl (equilibrium potential for Chloride), and this in turn determines whether GABA (the main inhibitory transmitter in the brain) would hyperpolarize (inhibit) or depolarize (excite) the cell.
The two chloride cotranporters, NKCC and KCC2, distribute differently in the retina. Although both are present in both synaptic layers (OPL and IPL), they are generally not present in the same cell compartment. For example, in OPL, KCC is present in OFF bipolar dendrites, and NKCC is present in ON bipolar dendrites. This diferential localization enables GABA to contribute to bipolar cells' receptive field surround by hyperpolarizing the OFF cells and depolarizing the ON cells.
It is interesting that the two transporters can be within a single cell, in two different compartments. For example, in ON bipolar cells, the dendrites express NKCC, but the axon terminals express KCC2. In the picture on the left, we marked the rod bipolar cells (ON cells) with anti-PKC (green) and localized KCC (red). The axons of these cell is green (does not localize KCC2), but the axon terminals is orange (does localize KCC2). In the picture on the right, we marked the ON bipolar dendrites with anti-mGluR6 (green) and localize NKCC (red). All ON bipolar dendrites are yellowish, indicating that they express NKCC.
Localization and function of Go
|Staining for the alpha subunit of Go - stain is localized to somas and dendrites of rod bipolar and ON cone bipolar cells.|
|wild type mouse stained for Go||G-alpha-o knockout mouse stain for Go.||Mouse that lacks the G-alpha-o subunit has no b-wave. (From Dhingra et al., 2000 J. Neuroscie, in press).|
Localization of mGluR6
|Punctate staining for mGluR6 in monkey retina. Stain is localized to dendritic tips of rod and ON cone bipola cells|
|Electronmicrograph showing staining for mGluR6. Stain is localized to the mouth of the invaginations, in apposition to cone electron-dense membrane.|
Monkey retina (cross section) immunostained for blue-sensitive opsin (red) and mGluR6 (green). mGluR6 is localized to dendritic tips of blue-sensitive bipolar cells..
Localization of GAD in rabbit horizontal cells
Rabbit retina immunoreacted for GAD65. Type A horizontal cell in the visual streak express GAD65, but those outside the visual streak do not.
Rabbit retina immunoreacted for GAD67. All horizontal cell terminals express this isoform.
Complete list of published work in my bibliography can be found at:
Husband, Avi (mathematician). Three gorgeous children: Eilat Vardi-Gonen (Ph.D student; computer science), Tamar Vardi (biologist), Amir Vardi (Wharton graduate; financial analyst).
|With Eilat at her wedding (1999).|
|Tamar (2004)||Tamar at Cardigen Lodge, Aug. 2005|
|At Amir's graduation (2004)||Amir with my dad (2006)|
|:Rain Gonen (born Sept, 19, 2004)|
|My darling is (from left to right) 4, 6, and 10 months old|
|8 months old with my mom||15 months old with a random puppy||21 months old|
|Oct. 2007 with dady Itamar||Dec. 2007 fun fun fun|
Rain got a brother, Jordan - born on Dec 18, 2009
|Rain is 6||Jordy is 2||and they become good friends|
|Eilat, Rain and Jordy, 2011||In LA, Apri 2011: Amir, Tamar, Eilat, Noga|
Amir and Dorian (Married )
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