Modeling stability in neuron and network function: the role of activity in homeostasis

Abstract

SummaryIndividual neurons display characteristic firing patterns determined by the number and kind of ion channels in their membranes. We describe experimental and computational studies that suggest that neurons use activity sensors to regulate the number and kind of ion channels and receptors in their membrane to maintain a stable pattern of activity and to compensate for ongoing processes of degradation, synthesis and insertion of ion channels and receptors. We show that similar neuronal and network outputs can be produced by a number of different combinations of ion channels and synapse strengths. This suggests that individual neurons of the same class may each have found an acceptable solution to a genetically determined pattern of activity, and that networks of neurons in different animals may produce similar output patterns by somewhat variable underlying mechanisms.

Animal-to-Animal Variability in Motor Pattern Production in Adults and during Growth

“…We know anecdotally that animal performance in both simple behaviors and complex cognitive tasks varies among individuals, but there are relatively few attempts to assess the degree of variance in network outputs in preparations in which it is possible to both characterize the network and to understand the cellular mechanisms that give rise to those outputs. This question is particularly interesting in the light of recent experimental and theoretical studies of homeostasis of cellular and synaptic properties in the nervous system (Stemmler and Koch, 1999;Turrigiano, 1999;Marder and Prinz, 2002;Turrigiano and Nelson, 2004). These studies suggest that the intrinsic excitability of single neurons and synaptic strengths are subject to slow homeostatic regulation that can stabilize neuronal function despite ongoing turnover of channels and receptors (LeMasson et al, 1993;Turrigiano et al, 1995;Davis and Goodman, 1998;Liu et al, 1998;Desai et al, 1999;Golowasch et al, 1999a,b;Davis and Bezprozvanny, 2001;Aizenman et al, 2003;MacLean et al, 2003;Zhang and Linden, 2003).…”

Robustness of Neural Coding inDrosophilaPhotoreceptors in the Absence of Slow Delayed Rectifier K+Channels

“…Despite their importance in regulating neural activity, genetic deletions of specific ion channels may produce relatively little change in performance, even when pharmacological or modeling studies suggest that the phenotypes should be severe (Liu et al, 1998;Namkung et al, 1998;Wickman et al, 1998;Akopian et al, 1999;Brickley et al, 2001;MacLean et al, 2003;Niven et al, 2003a). This robustness may be required to ensure that neurons maintain their response characteristics despite variable levels of channel expression (Goldman et al, 2001;Marder and Prinz, 2002;Niven, 2004). Indeed, recent work has shown that identified neurons in the crab stomatogastric ganglion generate similar outputs despite large fluctuations in K ϩ conductance densities between individuals (Liu et al, 1998;Golowasch et al, 1999;Prinz et al, 2003).…”

Observed network dynamics from altering the balance between excitatory and inhibitory neurons in cultured networks

“…In the brain, there are two types of neurons: excitatory and inhibitory, and it has been suggested that competition for excitatory and inhibitory inputs received by a neuron is essential for healthy brain activity [10]. The brain must operate within a range of activity for which external perturbations do not drive it into the pathological state and it is the balance between excitation and inhibition that maintains this dynamical state [11,12]. This balance is achieved in the cortex by an approximate ratio of 70% excitatory and 30% inhibitory neurons.…”