Faculty in Biology
Gautam Awatramani, Assistant Professor
Office: CUNN 259d Office Phone: 250-472-5178
Research areas: Synaptic physiology, multi-photon imaging, retina, optogenetics.
Fig 1. Top view of a GFP labelled ganglion cell population observed in a transgenic mouse retina. A) An individual cell is filled with a dye and then reconstructed after physiological recording. B) Cellular responses (spike rate histograms) of the cell shown in A to an image moving over its receptive field in 8 different directions. Note the cell responds most strongly when the image moves from left to right (preferred direction) because of its asymmetric shape and its connections to a specific neural circuit that codes image movement in this direction (Adapted from Trenholm et al., 2011).
Research in our lab aims to understand how specific elements of neural circuits in the brain interact through synapses to process relevant information. This is a considerable challenge since neurons are typically not isolated but entangled in an intricate mesh of overlapping circuits. To this end, we use mouse genetics to ‘light up’ specific circuits in the brain (Fig 1) with green fluorescent protein (GFP). One of the most accessible and anatomically well-defined parts of the brain is the retina. We use the retina as a model system to study the properties of synaptic interactions within specific genetically identified circuits. Amazingly, when carefully removed from the eye and placed in oxygenated salt and glucose-containing solutions, the retina continues to ‘see’. We can thus present pictures of all sorts to a little piece of retina placed under the microscope and directly observe how different circuit components extract relevant information, using 2-photon assisted patch-clamp techniques.
|Fig 2. A strategy for vision restoration in retina lacking conventional photoreceptors. Light-sensitive cells in wild type (wt) and the ‘rescued’ rd1 (mouse model for retinal degeneration) retina are highlighted. Using specific promoter sequences, GFP-tagged CHR2 can be selectively expressed in the ON bipolar cells (image on the right) and can restore light sensitivity to the downstream ON visual pathway (Adapted from Lagali et al., 2008)|
A second major emphasis in the lab is to develop optogenetic strategies to restore visual function during diseases that lead to the loss of photoreceptors and irreversible blindness. Optogenetic approaches utilize exogenous light sensitive molecules such as channelrhodopsin, to re-sensitize the retina to light after damage to the photoreceptor. By reprogramming remnant neurons of diseased retinas to play the role of missing photoreceptors (in the above illustrations ON bipolar cells (green) are endowed with light sensitivity), some vision can be partially restored in mice without photoreceptors.
Do email me if you are interested in opportunities in conducting research in retinal neurobiology.
Selected recent publications:
Trenholm S, Borowska JB, Zhang J, Hoggarth A, Johnson K, Barnes S, Lewis TJ and Awatramani GB (2012) Intrinsic oscillatory activity arising within the electrically-coupled AII amacrine/ON cone bipolar cell network is driven by voltage-gated Na+ channels JPhysiol 2012 Mar 5. [Epub ahead of print]
Trenholm S, Johnson K, Smith R and Awatramani GB (2011) Parallel mechanisms encode direction in the retina Neuron Aug 25;71(4):683-94.
Borowska JB, Trenholm S and Awatramani GB (2011) An intrinsic neural oscillator in the degenerating mouse retin JNeurosci 31(13):5000-12.
Münch T*, Azeredo da Silveira R*, Siegert S, Viney T, Awatramani G & Roska B (2009) Approach sensitivity in the retina processed by a multifunctional neural circuit. Nat Neurosci Oct;12(10):1308-16.
Balint K, Boldogkoi Z, Awatramani G, Viney T & Roska B (2009) Genetically timed, activity-sensor and rainbow transsynaptic viral tools Nat Methods 6(2):127-30.
Lagali P*, Balya D*, Awatramani GB*, Münch T, Kim D, Cepko C & Roska B (2008) Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration. Nat Neurosci 11(6):667-75.