Selective regulation of current densities underlies spontaneous changes in the activity of cultured neurons

Abstract

We study the electrical activity patterns and the expression of conductances in adult stomatogastric ganglion (STG) neurons as a function of time in primary cell culture. When first plated in culture, these neurons had few active properties. After 1 d in culture they produced small action potentials that rapidly inactivated during maintained depolarization. After 2 d in culture they fired large action potentials tonically when depolarized, and their properties resembled very closely the properties of STG neurons pharmacologically isolated in the ganglion. After 3–4 d in culture, however, their electrical properties changed and they fired in bursts when depolarized. We characterized the currents expressed by these neurons in culture. They included two TTX-sensitive sodium currents, a calcium current, a delayed-rectifier-like current, a calcium-dependent potassium current, and two A-type currents. The changes in firing properties with time in culture were accompanied by an increase in inward and decrease in outward current densities. A single-compartment conductance-based model of an STG neuron was constructed by fitting the currents measured in the biological neurons. When the current densities in the model neuron were matched to those measured for the biological neurons in each activity state, the model neuron closely reproduced each state, indicating that the changes in current densities are sufficient to account for the changes in intrinsic properties. These data indicate that STG neurons isolated in culture change their intrinsic electrical properties by selectively adjusting the magnitudes of their ionic conductances.

Added astroglia promote greater synapse density and higher activity in neuronal networks

“…Turrigiano has reported several mechanisms that coordinately regulate synaptic activity, a process termed synaptic scaling or homeostatic plasticity. In adult stomatogastric ganglion neurons in culture, a change from tonic to bursting action potentials is accompanied by changes in the ratio of inward:outward currents (Turrigiano et al, 1995). Deprivation of visual cortical activity downregulates GABAergic input through reduced BDNF (Rutherford et al, 1997); but BDNF-independent mechanisms also control quantal current amplitudes through postsynaptic polarization (Leslie et al, 2001).…”

Predictions of Phase-Locking in Excitatory Hybrid Networks: Excitation Does Not Promote Phase-Locking in Pattern-Generating Networks as Reliably as Inhibition

“…The membrane currents were based on voltage-clamp experiments on lobster stomatogastric neurons (Turrigiano et al 1995) and included a fast sodium current (I NaF ), a fast and a slow transient calcium current (I CaT and I CaS ), a fast transient potassium current (I A ), a calcium-dependent potassium current (I KCa ), a delayed rectifier potassium current (I Kd ), an H-type current (I H ), and a leak current (I leak ). The model neurons differed only in the maximal conductances of their eight membrane currents; these conductances were chosen to produce different burst periods and duty cycles in the different model neurons (Fig.…”

Calcium Channel Density and Hippocampal Cell Death with Age in Long-Term Culture

“…Critical developmental processes such as the appearance of neurotransmitters and ion channels, neurite outgrowth, synaptogenesis, and intrinsic firing patterns all depend in part on developmental changes in voltage-dependent C a 2ϩ conductances (Mattson and Kater, 1987;Gruol et al, 1992;Basarsky et al, 1994;Spitzer, 1994;Rusanescu et al, 1995;T urrigiano et al, 1995).…”