Propagating Neuronal Discharges in Neocortical Slices: Computational and Experimental Study

Abstract

We studied the propagation of paroxysmal discharges in disinhibited neocortical slices by developing and analyzing a model of excitatory regular-spiking neocortical cells with spatially decaying synaptic efficacies and by field potential recording in rat slices. Evoked discharges may propagate both in the model and in the experiment. The model discharge propagates as a traveling pulse with constant velocity and shape. The discharge shape is determined by an interplay between the synaptic driving force and the neuron's intrinsic currents, in particular the slow potassium current. In the model, N-methyl-D-aspartate (NMDA) conductance contributes much less to the discharge velocity than amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) conductance. Blocking NMDA receptors experimentally with 2-amino-5-phosphonovaleric acid (APV) has no significant effect on the discharge velocity. In both model and experiments, propagation occurs for AMPA synaptic coupling gAMPA above a certain threshold, at which the velocity is finite (non-zero). The discharge velocity grows linearly with the gAMPA for gAMPA much above the threshold. In the experiments, blocking AMPA receptors gradually by increasing concentrations of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the perfusing solution results in a gradual reduction of the discharge velocity until propagation stops altogether, thus confirming the model prediction. When discharges are terminated in the model by the slow potassium current, a network with the same parameter set may display discharges with several forms, which have different velocities and numbers of spikes; initial conditions select the exhibited pattern. When the discharge is also terminated by strong synaptic depression, there is only one discharge form for a particular parameter set; the velocity grows continuously with increased synaptic conductances. No indication for more than one discharge velocity was observed experimentally. If the AMPA decay rate increases while the maximal excitatory postsynaptic conductance (EPSC) a cell receives is kept fixed, the velocity increases by approximately 20% until it reaches a saturated value. Therefore the discharge velocity is determined mainly by the cells' integration time of input EPSCs. We conclude, on the basis of both the experiments and the model, that the total amount of excitatory conductance a typical cell receives in a control slice exhibiting paroxysmal discharges is only approximately 5 times larger than the excitatory conductance needed for raising the potential of a resting cell above its action potential threshold.

Traveling waves and pulses in a one-dimensional network of excitable integrate-and-fire neurons

“…We also establish that for fast solitary waves the velocity scales as some power of the synaptic strength g with c 0 ∼ √ g for synaptic delays and c 0 ∼ g 2 for dendritic delays. This suggests that the approximately linear relationship observed experimentally (Golomb and Amitai 1997) might arise from some combination of these two aspects.…”

“…Second, it establishes that the velocity of a wave is approximately independent of wavelength (at least for long wavelength solutions). This is at least suggestive of the approximate velocity-independence of the various discharge patterns observed in more detailed computational models (Golomb and Amitai 1997). As highlighted by Ermentrout (1998), a major unsolved problem is the detailed nature of the effects of re-excitation on wave propagation.…”

“…These various studies indicate that wave propagation in cortical (and hippocampal) slices only occurs if the synaptic strength of neuronal interactions exceeds some threshold; well beyond threshold the velocity is approximately linear in the coupling (see eg. Golomb and Amitai 1997). Moreover, multiple forms of discharge patterns are observed to propagate at the same parameter values.…”

“…A number of recent experimental studies have revealed the propagation of traveling bursts of activity in slices of excitable neural tissue taken from the cortex (Chervin et al 1988;Golomb and Amitai 1997), hippocampus (Traub et al 1993) and thalamus (Kim et al 1995;Golomb et al 1996;Destexhe et al 1996). The underlying mechanism for propagation of these waves is thought to be synaptic in origin rather than diffusive as in the propagation of action potentials.…”

“…The underlying mechanism for propagation of these waves is thought to be synaptic in origin rather than diffusive as in the propagation of action potentials. Computational models of synaptically generated waves have also been developed, in which neural tissue is treated as a one-dimensional continuum (Traub et al 1993;Golomb et al 1996;Destexhe et al 1996: Golomb andAmitai 1997). These various studies indicate that wave propagation in cortical (and hippocampal) slices only occurs if the synaptic strength of neuronal interactions exceeds some threshold; well beyond threshold the velocity is approximately linear in the coupling (see eg.…”