Homeostatic synaptic plasticity: from single synapses to neural circuits

Abstract

Homeostatic synaptic plasticity remains an enigmatic form of synaptic plasticity. Increasing interest on the topic has fuelled a surge of recent studies that have identified key molecular players and the signaling pathways involved. However, the new findings also highlight our lack of knowledge concerning some of the basic properties of homeostatic synaptic plasticity. In this review we address how homeostatic mechanisms balance synaptic strengths between the presynaptic and the postsynaptic terminals and across synapses that share the same postsynaptic neuron.

Figure 1

Co-ordination of synaptic strengths across a network. (a) Representative scheme of three connected neurons. A postsynaptic neuron (yellow) receives inputs from two presynaptic neurons (red and blue) across its dendritic arbor. How heterosynaptic interactions between the red and the blue inputs occur at the level of individual synapses is not known. The scheme in (b) illustrates, at the synapse resolution, a possible interaction between a synapse belonging to the red input undergoing LTP and another (near or distant) synapse from the blue input showing compensatory depression. One possible mechanism involved in the heterosynaptic interaction is the spreading of Ca²⁺-dependent signaling molecules. (c) Retrograde signaling involved in matching of the presynaptic and the postsynaptic strengths under chronic synaptic activity blockade. This mechanism involves the postsynaptic accumulation of β-CaMKII and surface GluA1-containing AMPARs, followed by the postsynaptic release of BDNF and NO, and the subsequent increase in synaptic vesicle recycling.