Wherefore Art Thou, Homeo(stasis)? Functional Diversity in Homeostatic Synaptic Plasticity

Abstract

Homeostatic plasticity has emerged as a fundamental regulatory principle that strives to maintain neuronal activity within optimal ranges by altering diverse aspects of neuronal function. Adaptation to network activity is often viewed as an essential negative feedback restraint that prevents runaway excitation or inhibition. However, the precise importance of these homeostatic functions is often theoretical rather than empirically derived. Moreover, a remarkable multiplicity of homeostatic adaptations has been observed. To clarify these issues, it may prove useful to ask: why do homeostatic mechanisms exist, what advantages do these adaptive responses confer on a given cell population, and why are there so many seemingly divergent effects? Here, we approach these questions by applying the principles of control theory to homeostatic synaptic plasticity of mammalian neurons and suggest that the varied responses observed may represent distinct functional classes of control mechanisms directed toward disparate physiological goals.

Polo-like kinase 2 phosphorylation of amyloid precursor protein regulates activity-dependent amyloidogenic processing

“…Chronic synaptic overactivity induces somatodendritic expression of Plk2, which binds directly to the intracellular tail of APP and phosphorylates T668/S675, stimulating endocytosis of surface APP and subsequent Aβ production. This mechanism occurs over a slow time course, concordant with the observation that many forms of homeostatic plasticity occur on relatively slow timescales (reviewed in Queenan et al, 2012). On a molecular level, this delay may reflect the time required to induce Plk2 expression, ~6–12 hrs (Seeburg and Sheng, 2008).…”

Mapping homeostatic synaptic plasticity using cable properties of dendrites

“…The “synaptic scaling” model (4) proposes that all synapses are homeostatically adjusted by the same proportion, thus preserving relative weights. Many studies support this theory, while others are inconsistent with the model (9). The question remains: does HSP scale globally along dendrites?…”

Sucrose-induced plasticity in the basolateral amygdala in a ‘comfort’ feeding paradigm

“…Synaptic currents were analyzed for changes in mean frequency, amplitude and decay time (defined as the elapsed time from the peak to 63% decay to baseline) using the Minianalysis 6.0 program (Synaptosoft Inc., Decatur, GA). The frequency of miniature synaptic currents primarily reflects the probability of spontaneous (unstimulated) presynaptic neurotransmitter release and/or the number of presynaptic release sites (Queenan et al 2012); the amplitude primarily reflects the postsynaptic response (Queenan et al 2012); and the decay time primarily reflects the amount of neurotransmitter clearance/reuptake and receptor desensitization (Takahashi et al 1995). …”