Figure 1.

Mammalian Ca_V1 and Ca_V2 channels play central roles in forms of homeostatic plasticity. These two cartoons attempt to synthesize knowledge of mammalian pre- and postsynaptic homeostatic plasticity mechanisms involving Ca_V1 and Ca_V2 calcium channels in preparations like cultured hippocampal neurons. The cartoons are not intended to depict a single synaptic preparation or universally conserved mechanism, though some molecular responses may be widely conserved. (A) Homeostatic potentiation of synapse function. Inhibition of synaptic activity or postsynaptic Ca_V1 calcium influx results in multiple changes, including postsynaptic signaling through molecules like adenylate cyclase 1 (AC1) or guanylate kinase-associated protein (GKAP) to drive activating mechanisms, such as glutamate receptor insertion. Trans-synaptic signaling controlled by factors like Target of Rapamycin (TOR) and Brain-Derived Neurotrophic Factor (BDNF) can trigger enhanced presynaptic release probability. From a variety of systems there is evidence for enhanced presynaptic calcium influx through Ca_V2—which may require diminishment of cyclin-dependent kinase 5 (CDK5) function—as well as an enhanced readily releasable pool of presynaptic vesicles. (B) Homeostatic downscaling of synapse function. Synaptic activation (e.g., through GABA receptor blockade) and/or enhanced postsynaptic calcium influx through Ca_V1 results in the activation of diverse pathways, such as those mediated by calcium/calmodulin-dependent kinases (CaMK), as well as the Protein Phosphatase 1 (PP1) inhibitor, I-2. This can result in removal of excitatory glutamate receptors from the synapse. Presynaptically, there is evidence of diminished calcium influx through Ca_V2, and thus, diminished evoked presynaptic release.