HOMEOSTATIC CONTROL OF NEURAL ACTIVITY: From Phenomenology to Molecular Design

Abstract

Homeostasis is a specialized form of regulation that precisely maintains the function of a system at a set point level of activity. Recently, homeostatic signaling has been suggested to control neural activity through the modulation of synaptic efficacy and membrane excitability ( Davis & Goodman 1998a, Turrigiano & Nelson 2000, Marder & Prinz 2002, Perez-Otano & Ehlers 2005 ). In this way, homeostatic signaling is thought to constrain neural plasticity and contribute to the stability of neural function over time. Using a restrictive definition of homeostasis, this review first evaluates the phenomenological and molecular evidence for homeostatic signaling in the nervous system. Then, basic principles underlying the design and molecular implementation of homeostatic signaling are reviewed on the basis of work in other, simplified biological systems such as bacterial chemotaxis and the heat shock response. Data from these systems are then discussed in the context of homeostatic signaling in the nervous system.

Time scales of memory, learning, and plasticity

“…Here, the synaptic efficiency of all inputs to a neuron increases/ decreases if the activity of this neuron is lower/higher than a target activity (Davis 2006). These changes happen on a time scale of days.…”

Isolation rearing impairs wound healing and is associated with increased locomotion and decreased immediate early gene expression in the medial prefrontal cortex of juvenile rats

“…Homeostatic synaptic plasticity and synaptic scaling (Davis 2006) suggest that altered neuronal plasticity, such as that reflected by increased or decreased IEG expression, is optimized by compensatory changes that affect neuronal activity. For example, decreased Arc expression due to TTX application (which blocks the voltage sensitive sodium channel) results in increased AMPA receptor expression (Shepherd, Rumbaugh et al 2006).…”

Spinal cord - skeletal muscle cocultures detect muscle-relaxant action of botulinum neurotoxin A

“…Therefore, it seems unlikely that incobotulinumtoxin A was capable of attenuating the frequency of muscle contractions via this route. However, there is ample evidence in the literature that a depression of synaptic transmission produced by pharmacologic interventions evokes homeostatic responses and changes neuronal excitability on a slow time scale (Davis, 2006;Galante et al, 2000;turrigiano, 1999). thus, a modulating botulinum effect at the neuromuscular junction might be veiled by alterations of glutamate transmitter release in the spinal ventral horn, where locomotor activity is triggered.…”