There are two main molecular mechanisms for synaptic restructure. The first mechanism involves modification of existing synaptic proteins (typically protein kinases) resulting in altered synaptic function. The second mechanism depends on second messenger neurotransmitters regulating gene transcription and changes in the levels of key proteins at synapses. This second mechanism can be triggered by protein phosphorylation, but takes longer, providing the mechanism for longlasting memory storage. Long-lasting changes in the efficacy of synaptic connections (long term potentiation, or LTP) between two neurons can involve the making and breaking of synaptic contacts. Several facts suggest that neurons change the density of receptors on their postsynaptic membranes as a mechanism for changing their own excitability in response to stimuli. In a dynamic process that is maintained in equilibrium, NMDA and AMPA receptors are added to the membrane by exocytosis and removed by endocytosis, that can be altered by synaptic activity. If the strength of a synapse is only reinforced by stimulation or weakened by its lack, a positive feedback loop will develop, but two regulatory forms of plasticity, called scaling and metaplasticity, also exist to provide negative feedback. Synaptic scaling serves to maintain the strengths of synapses relative to each other, lowering amplitudes of small excitatory postsynaptic potentials. Metaplasticity instead reduces the effects of plasticity over time and since LTP and LTD (long term depression) rely on the influx of Ca2+ through NMDA channels, metaplasticity may be due to changes in NMDA receptors. Three major hypotheses for the molecular nature of this plasticity have been wellstudied, and none are required to be the exclusive mechanism: a) change in the probability of glutamate release b) insertion or removal of postsynaptic AMPA receptors and c) phosphorylation and de-phosphorylation inducing a change in AMPA receptor conductance. The first two hypotheses have been recently mathematically examined to have identical calcium-dependent dynamics; in a linear model it can be expressed as follows: DWi(t)/dt={1/τ([Ca2+])}*(Ω[Ca2+]i)Wi, where Wi is the synaptic weight of the ith input axon, τ is a time constant dependent on the insertion and removal rates of neurotransmitter receptors, which is dependent on [Ca2 + ]. Ω=βAfp m is also a function of the concentration of calcium that depends linearly on the number of the receptors on the membrane of the neuron at some fixed point. The model makes important simplifications that make it unsuited for actual experimental predictions, but provides a significant basis for the hypothesis of a calcium-based synaptic plasticity dependence.