Lab Meeting: the Highlights ofAudrey’s Amacrine Paper (Submitted, J. Neurophys)

Audrey RoyerJanuary 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

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

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