Action Potentials: To the Nucleus and Beyond

Abstract

The neuronal nucleus is now widely accepted as playing a vital role in maintaining long-term changes in synaptic effectiveness. To act, however, the nucleus must be appropriately relayed with information regarding the latest round of synaptic plasticity. Several constraints of doing so in a neuron pertain to the often significant spatial distance of synapses from the nucleus and the number of synapses required for such a signal to reach functional levels in the nucleus. Largely based on the sensitivity of transcriptional responses to NMDA receptor antagonists, it has been postulated that the signals are physically relayed by biochemical messengers from the synapse to the nucleus. Alternatively, a second, less often considered but equally viable method of signal transduction may be initiated by action potentials generated proximal to the nucleus, wherefrom the signal can be relayed directly by calcium or indirectly by biochemical second messengers. We consider action potential-dependent signaling to the nucleus to have its own computational advantages over the synapse-to-nucleus signal for some functions. This minireview summarizes the logic and experimental support for these two modes of signaling and attempts to validate the action potential model as playing an important role in transcriptional regulation relating specifically to long-term synaptic plasticity.

Parent-of-origin genetic background affects the transcriptional levels of circadian and neuronal plasticity genes following sleep loss

“…Calcium is widely known to be a major player in neuronal intracellular communication and signalling processes capable of activating and promoting gene transcription in the nucleus. regulates the transcription of genes involved in synaptic plasticity, memory and cell survival [38][39][40][41]. BDNF is largely expressed in the nervous system [42].…”

γCaMKII Shuttles Ca2+/CaM to the Nucleus to Trigger CREB Phosphorylation and Gene Expression

“…This CaM/CaMK-based system adds to known mechanisms for signaling between neuronal (e.g. postsynaptic) membrane and nucleus (Ch’ng and Martin, 2011; Hagenston and Bading, 2011; Jordan and Kreutz, 2009; Saha and Dudek, 2008). The present mechanism likely tracks neuronal depolarization rather than synaptic activity per se , as is likely for the NMDAR-driven transcription factors NFκB (Meffert et al, 2003), Jacob (Karpova et al, 2013) and CRTC1/TORC1 (Ch’ng et al, 2012).…”

Molluscan Memory of Injury: Evolutionary Insights into Chronic Pain and Neurological Disorders

“…Initiating events for long-term alterations include intense depolarization and Ca 2+ entry consequent to membrane injury or binding of excitatory amino acids, and activation of cell signaling pathways by binding of neuromodulators and growth factors released by neurons [Jankowsky and Patterson, 1999;Kandel, 2001;Weragoda and Walters, 2007] and other cell types [e.g., glia, support cells, and inflammatory cells; Bradley and Finkbeiner, 2002;Gibbs et al, 2008]. Changes in gene expression are triggered by Ca 2+ entry accompanying action potentials propagating into the soma [Saha and Dudek, 2008], as well as retrograde signals transported to the nucleus from sites of axonal injury [Gunstream et al, 1995;Lin et al, 2003; or intense synaptic stimulation [Otis et al, 2006;Lai et al, 2008]. Long-term alterations can include effects localized to sites of injury or to intensely activated synapses, as well as global actions affecting much of the neuron from neural or endocrine signals released throughout the body during either injury or the formation of central memories.…”