The Mechanisms by which cell geometry controls repetitive impulse firing in
Retinal Ganglion Cells.
Fohlmeister, J.F. and Miller, R.F.
Physiology Department, University of Minnesota, Minneapolis, MN 55455.
APStracts 4:0097N, 1997.
ABSTRACT
Models for generating repetitive impulse activity were developed, based on
multicompartmental representations of ganglion cell morphology in the
amphibian retina. Each model includes five non-linear ion channels and one
linear (leakage) channel. Compartmental distribution of ion channel type and
density was designed to simulate whole-cell recording experiments carried out
in the intact retina-eyecup preparation. Correspondence between the model and
physiology emphasized channel-specific details in the impulse waveform, based
on phase plot analysis, frequency vs current (F/I) properties and interspike
trajectories for current injected into the soma, as well as the ability to
conduct impulses in both orthodromic and antidromic directions. Two general
types of model are developed, including equivalent cylinder representations
and more realistic compartmentalizations of dendritic morphology. These
multicompartmental models include representations for dendritic trees, soma,
axon hillock, a thin axonal segment, and axon distal to thin segment. A large
number of compartments (up to 800) representing a single neuron were employed
to ensure that maximum voltage differences between neighboring compartments
during the steepest rates of change of membrane potential were acceptably
small. Leakage conductance varied from 3 to 8 ęS/cm2. The results establish
that intercompartmental currents, due to inhomogeneous morphology, dominate
membrane currents in the interspike intervals, and thus play a major role in
determining the impulse spacing and the information carried by impulse trains.
Variations in input resistance is far less important than the degree to which
ion channels are present in the dendritic compartments for the regulation of
F/I properties. Cell geometry, including the thin axonal segment, places
significant constraints on the location of ion channels required to support
impulse initiation and propagation in both the ortho and antidromic
directions. The site of impulse initiation varies greatly, and depends on the
stimulus magnitude. Models which conform to physiological constraints also
show irregular firing, particularly for near threshold stimulation of the
soma, due to multiple sites of impulse initiation. Such behavior could
represent an asset to the cells for conveying information under conditions of
low contrast stimulation. Multiple spike initiation zones can also provide
retinal ganglion cells with a variety of response characteristics, including
spike doublets, depending on the level of cell activation. Increasing the
diameter of the dendritic equivalent cylinder reduces the impulse frequency
(F/I) response. Over a restricted range of ion channel densities in the
dendritic tree, phase locking between dendritic membrane oscillations and
somatic spiking can occur with dendritic stimulation, and mathematical chaos
can be demonstrated when sufficiently thin dendritic processes are present. We
conclude that cell morphology is the primary factor in determining firing
patterns and the impulse frequency response of a given cell, and that
differences in channel density distribution accross a population of cells
plays at most a secondary role in this function. This conclusion applies to
both synaptic activation and electrode stimulation of the soma.
Received 1 April 1996; accepted in final form 13 June 1997.
APS Manuscript Number J270-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 15 July 1997