Abstract
Synapses on dendritic spines of pyramidal neurons show a remarkable ability to induce phosphorylation of transcription factors at the nuclear level with a short latency, incompatible with a diffusion process from the dendritic spines to the nucleus. To account for these findings, we formulated a novel extension of the classical cable theory by considering the fact that the endoplasmic reticulum (ER) is an effective charge separator, forming an intrinsic compartment that extends from the spine to the nuclear membrane. We use realistic parameters to show that an electrotonic signal may be transmitted along the ER from the dendritic spines to the nucleus. We found that this type of signal transduction can additionally account for the remarkable ability of the cell nucleus to differentiate between depolarizing synaptic signals that originate from the dendritic spines and back-propagating action potentials. This study considers a novel computational role for dendritic spines, and sheds new light on how spines and ER may jointly create an additional level of processing within the single neuron.
Highlights
Glutamatergic synaptic inputs onto dendritic spines of pyramidal neurons induce phosphorylation of the transcription factor CREB in the nucleus [1,2,3]
Our study incorporates the fact that the endoplasmic reticulum (ER) forms a complete continuum from the spine head to the nuclear envelope and suggests that electrical current flow in a neuron may be better described by a cable-within-a-cable system, where synaptic current flows simultaneously in the medium between the cell membrane and the ER, and within the ER
Our paper provides a novel extension to the classical cable theory and presents several interesting predictions
Summary
Glutamatergic synaptic inputs onto dendritic spines of pyramidal neurons induce phosphorylation of the transcription factor CREB (cAMP-Responsive-Element Binding protein) in the nucleus [1,2,3]. Several studies [1,2,3,7,8] have aimed at finding the spine-to-nucleus signaling involved in CREB phosphorylation that enables the nucleus to discriminate between orthodromic and antidromic signals. The nature of this signal transduction, remained unclear. Since the Ca2+-Calmodulin complex (Ca2+/CaM) is readily generated in the spine during synaptic activity and since activity-dependent CREB phosphorylation follows translocation of Ca2+/CaM from cytosol to nucleus, Ca2+/CaM diffusion was suggested to carry the spine-tonucleus signal [3,8]. Mermelstein et al have suggested that CaM diffuses in a phosphorylated form, which can reach 20 mm during 15 seconds due to an increased cytoplasmic diffusion rate
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