New modification rules for neural networks with excitatory and inhibitory synaptic connections

The existence of Hebbian-like learning rules was supported by numerous experiments on excitatory glutamatergic synapses. Two forms of long-term modification of excitatory synaptic transmission-potentiation (LTPe) and depression (LTDe) were demonstrated. Both effects are input specific, depend on correlation between presynaptic activity and postsynaptic response, and require increase in postsynaptic Ca⁺⁺ ion concentration (Ca⁺⁺_p). There are experimental evidences that the large surge in Ca⁺⁺_p (designed Ca⁺⁺_l) triggers LTPe by activation of Ca⁺⁺-dependent protein kinases (PKs), phosphorylation of ionotropic AMPA and NMDA receptors (AMPARs, NMDARs), and increasing of their sensitivity. The moderate elevation of Ca⁺⁺ _p (designed Ca⁺⁺_m) leads to LTDe by Ca⁺⁺-dependent on (by the use of calcineurin) activation of protein phosphatases (PPs), dephosphorylation of AMPARs and NMDARs, and decrease of their sensitivity. Thus the balance between PKs and PPs determine the type of excitatory transmission modification