Lab Meeting: the Highlights of Audrey’s Amacrine Paper (Submitted, J 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 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 I K  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

Area Summation Receptive Fields Walk through how D put together. Flip back to figure 3. Receptive fields less than predicted.

Saturation of the Soma with Passive Dendrites

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 Not whole story. 100pS - all active saturated at 89%, all passive cell saturated at 75%. 14% difference from AP shift. What preventing 11%? Initiating dendritic APs in the distal dendrites allowed the all active 100pS cell to summate 14% more charge than its all passive counterpart, but another factor prevented the summation of the remaining 11%.

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