Figure 1. Cable-in-cable hypothesis.

(A) The principal hypothesis: synaptic activation onto a dendritic spine, generates two simultaneous currents, along the cytoplasmic compartment and along the ER lumen. These currents generate two passive electrotonic signals, across the plasma membrane (outer cable) and across the ER membrane (the inner cable). Consequently, synaptic activity at the spine can signal electrotonically-fast to the nucleus. (B) The model describes a passive system of a cable within cable where the internal cable represents the ER-lumen confined by ER-membrane and a cytosolic compartment surrounded by plasma membrane. The model also assumes a non-conductive cross section representing various intracellular organelles. (C) The cable-in-cable model provides an analytical solution for a system constructed of iso-potential circuit elements of length dx. The circuit describes three semi-infinite compartments: external (V _e), cytosolic (V _i), and ER (V _ER), which are separated by two membranes, represented by a resistor (R _m) and a capacitor (C _m) in parallel. The circuit further defines the positive direction of currents. A similar two layer circuit has been employed previously for modeling non-passive signaling along myelinated axon [69].