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Lab Meeting: the Highlights of Audrey’s Amacrine Paper (Submitted, J. Neurophys). Audrey Royer January 12, 2007. Amacrine Cell Modeling. Began as a rotation project Objective: reproduce previously published electrophysiological data with a computer model
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Lab Meeting: the Highlights ofAudrey’s Amacrine Paper (Submitted, J. Neurophys) Audrey Royer January 12, 2007
Amacrine Cell Modeling • Began as a rotation project • Objective: reproduce previously published electrophysiological data with a computer model • Objective achieved, written up, and submitted as a paper • Paper was firmly and rightfully rejected • What contribution did the paper make to the scientific community?
Amacrine Cell Modeling – Round 2 • Used reviewers’ feedback to expand modeling • Why did these new results not agree with previous results? • Investigation into discrepancy led to novel discovery • Could only have been found through modeling • Explains electrophysiological data • New paper written and submitted on 11/29/06
Dendritic impulse collisions and shifting sites of action potential initiation contract and extend the receptive field of an amacrine cell
Problem • Amacrine cells only retinal neurons with observable dendritic action potentials (AP) • APs needed to laterally spread inhibition over more than 250 um (Cook et al. 1998) • Receptive field size (Bloomfield 1992, 1996) • Approximates dendritic tree • Significantly reduced in the presence of TTX (Na channel blocker) • Evaluate influence of dendritic APs on receptive field properties of amacrine cells
Why Modeling? • Electrophysiological data obtained from soma • Sometimes from proximal dendrites • Very limited view of the electrical activity of the cell
Methods • NEURON computer program • I Na • IK • I K, A • I K, Ca • I Ca • I Leak
Annular Data • Voltage recording in soma • Somatic and dendritic APs • Active dendrites: all annuli capable of influencing soma • Dendritic spikes same amplitude in A and D • Passive dendrites: annuli 300 um no effect on soma
Cumulative Annular Injected Charge • Points of interest: • Shapes of graphs • Where each model reaches 100% • Used to predict receptive field size in area summation simulations
Area Summation Data • Somatic response increases until it saturates • Active dendrites saturate later than passive dendrites • Larger receptive field
Active Dendrites Prevent Saturation –Shifting Sites of Impulse Initiation
Impulse Collisions Reduce Influence of Distal Dendrites in Area Summation Sims • As increased peak synaptic conductance, increased number of APs • APs started to overlap in time course and interact • Collisions • Refractory • Interactions reduced influence of distal dendritic APs
References • Bloomfield SA. Relationship between receptive and dendritic field size of amacrine cells in the rabbit retina. J Neurophysiol 68: 711-725, 1992. • Bloomfield SA. Effect of spike blockade on the receptive-field size of amacrine and ganglion cells in the rabbit retina. J Neurophysiol 75: 1878-1893, 1996. • Cook PB, Lukasiewicz PD and McReynolds JS. Action potentials are required for the lateral transmission of glycinergic transient inhibition in the amphibian retina. J Neurosci 18: 2301-2308, 1998.
After Accounting for Collisions, Annular Data Predicts Area Summation Receptive Fields