Somatic action potentials are sufficient for late-phase LTP-related cell signaling

Abstract

A question of critical importance confronting neuroscientists today is how biochemical signals initiated at a synapse are conveyed to the nucleus. This problem is particularly relevant to the generation of the late phases of long-term potentiation (LTP). Here we provide evidence that some signaling pathways previously associated with late-LTP can be activated in hippocampal CA1 neurons without synaptic activity; somatic action potentials, induced by backfiring the cells, were found to be sufficient for phosphorylation of extracellular signal-regulated kinase-1/2 and cAMP response element-binding protein, as well as for induction of zif268. Furthermore, such antidromic stimulation was adequate to rescue ''tagged'' synapses (early-LTP) from decay. These results show that a synapse-to-nucleus signal is not necessary for late-phase LTPassociated signaling cascades in the regulation of gene expression.

Identification of Compartment- and Process-Specific Molecules Required for “Synaptic Tagging” during Long-Term Potentiation and Long-Term Depression in Hippocampal CA1

“…Basal dendrites with their close relation to the soma (Fig. 7) may regulate a neuron-wide synthesis of PRPs, possibly via a direct activation of gene expression (Dudek and Fields, 2002;Adams and Dudek, 2005;Reymann and Frey, 2007), thus providing a cellular mechanism for a general increase in the capacity to store relevant information within the neuron.…”

“…How PRPs interact only with activated synapses expressing LTP or LTD is fundamental to synapse specificity of the process and can be explained by the "synaptic tagging" hypothesis . Synaptic tagging has also been shown by other laboratories (Barco et al, 2002;Dudek and Fields, 2002;Fonseca et al, 2004;Young and Nguyen, 2005), and it was described for LTD (Kauderer and Kandel, 2000;Sajikumar and Frey, 2004a) and for invertebrates (Casadio et al, 1999).…”

“…However, field stimulation in the stratum oriens may also partially activate CA1 axons (i.e., activating antidromically the target cells). This somatic stimulation could lead to a facilitation of plastic events in the stratum radiatum (Dudek and Fields, 2002;Adams and Dudek, 2005). Another possibility is that the requirements for inducing prolonged forms of plastic events in the basal dendrites may differ from those in the apical dendrites (LTP; see below, LTP in basal CA1 dendrites).…”

Mechanisms of heterosynaptic metaplasticity

“…Here, the duration of LTD/LTP is centrally regulated by protein synthesis such that prior neural activity facilitates rather than impairs LTP heterosynaptically [22]. In this model, a pool of proteins required for consolidation of LTD and LTP can be made available by suitably strong afferent stimulation, or even by simply postsynaptic spiking [23,24]. Crucially, the capture and usage of these proteins can occur at heterosynaptic locations where there is only relatively weak synaptic activity that is normally insufficient to induce the late phase of synaptic plasticity.…”

The Role of Functional Prion-Like Proteins in the Persistence of Memory

“…The model of a "synaptic tag," whereby gene products are delivered to all synapses but are only used at synapses that have been tagged, has been supported by a number of studies both in Aplysia (Figs. 3 and 4) (Martin et al 1997b;Casadio et al 1999) and in the rodent hippo- campus Morris 1997, 1998;Barco et al 2002;Dudek and Fields 2002).…”