Persistent Sodium Current Is a Nonsynaptic Substrate for Long-Term Associative Memory

Abstract

Although synaptic plasticity is widely regarded as the primary mechanism of memory [1], forms of nonsynaptic plasticity, such as increased somal or dendritic excitability or membrane potential depolarization, also have been implicated in learning in both vertebrate and invertebrate experimental systems [2-7]. Compared to synaptic plasticity, however, there is much less information available on the mechanisms of specific types of nonsynaptic plasticity involved in well-defined examples of behavioral memory. Recently, we have shown that learning-induced somal depolarization of an identified modulatory cell type (the cerebral giant cells, CGCs) of the snail Lymnaea stagnalis encodes information that enables the expression of long-term associative memory [8]. The Lymnaea CGCs therefore provide a highly suitable experimental system for investigating the ionic mechanisms of nonsynaptic plasticity that can be linked to behavioral learning. Based on a combined behavioral, electrophysiological, immunohistochemical, and computer simulation approach, here we show that an increase of a persistent sodium current of this neuron underlies its delayed and persistent depolarization after behavioral single-trial classical conditioning. Our findings provide new insights into how learning-induced membrane level changes are translated into a form of long-lasting neuronal plasticity already known to contribute to maintained adaptive modifications at the network and behavioral level [8].

A Homolog of the Vertebrate Pituitary Adenylate Cyclase-Activating Polypeptide Is Both Necessary and Instructive for the Rapid Formation of Associative Memory in an Invertebrate

“…A model of the PACAP-activated molecular cascades of memory formation after food-reward classical conditioning in Lymnaea Previous molecular, behavioral, pharmacological, and electrophysiological analyses already have identified a number of receptors, ion channels, and signaling molecules involved in the acquisition as well as early and/or late consolidation of associative LTM after food-reward classical conditioning in Lymnaea Ribeiro et al, 2003Ribeiro et al, , 2005Ribeiro et al, , 2008Fulton et al, 2005;Korneev et al, 2005;Michel et al, 2008;Nikitin et al, 2008;Wan et al, 2010). Our new findings have now made it possible to construct a model of the interacting components involved in the formation of long-term associative memory after foodreward classical conditioning in Lymnaea (Fig.…”

“…Previous work in our laboratory and by others has shown that activation of NMDA receptors is necessary for the formation of associative LTM in invertebrates [Aplysia, Murphy and Glanzman (1999); Drosophila, Xia et al (2005); Lymnaea, Jami et al (2007), Wu et al (2007), and Wan et al (2010)], and we now hypothesize that invertebrate PACAP-like peptides play a mechanistic role in the learninginduced activation of NMDA receptors similar to that previously described in the hippocampus. , and K ϩ channels, Staras et al (2002) and Nikitin et al (2008); NOS and NO, Kemenes et al (2002) and Korneev et al (2005); PKA, G. ; RNA and protein synthesis, Fulton et al (2005); sGC, Ribeiro et al (2008) and Michel et al (2008)], are shown boxed. G, G-Protein; DA, dopamine; 5-HT,serotonin;MAPK,mitogen-activatedproteinkinase;CaMKII,calcium/calmodulin-dependentkinaseII;NOS,nitricoxidesynthase;NO, nitric oxide; sGC, soluble guanylyl cyclase; PKG, cGMP-activated protein kinase; PCREB, phosphorylated cAMP response element-binding protein; C/EBP, CCAAT enhancer-binding protein.…”

Previous motor activity affects transition from uncertainty to decision-making in snails

“…Lymnaea stagnalis snails have been used extensively for the analysis of cellular and molecular mechanisms of locomotion (Syed and Winlow, 1991b;Pavlova, 2010;Longley and Peterman, 2013), feeding (Benjamin and Rose, 1979;Elliott and Benjamin, 1989;Kemenes and Elliott, 1994;Staras et al, 1998Staras et al, , 2003Alania et al, 2004;Vehovszky et al, 2005;Vavoulis et al, 2007;Chistopolsky and Dyakonova, 2012), respiration (Syed and Winlow, 1991a,b;Tsyganov et al, 2004;Bell et al, 2007), learning and memory (Kemenes et al, 1997(Kemenes et al, , 2002Kojima et al, 1997;Spencer et al, 1999;Staras et al, 1998;Jones et al, 2003;Sangha et al, 2003;Kemenes et al, 2006;Nikitin et al, 2008;Marra et al, 2013;Mita et al, 2014;Naskar et al, 2014), and decision making (Pirger et al, 2014;Crossley et al, 2016). There are also approaches that have been developed only in this organism, particularly the studies at the single-cell level of freshly isolated, not cultured, neurons (Dyakonova et al, 2009(Dyakonova et al, , 2015Dyakonova and Dyakonova, 2010), and experimental tests of an extracellular chemical microenvironment that has been demonstrated to play a prominent 'socializing' role in adjusting single-cell physiology to the network state (Dyakonova et al, 2015).…”

Find synaptic topology from spike trains

“…In the current paper, we have found a way to recover the network topology using spiking data. However, the topology is static and does not reflect the interesting dynamics of learning [6], [7]. It is certainly one of our future research topics: using sliding windows to reconstruct a dynamical network topology.…”

“…Undoubtedly, the relation between the spike activities and the synaptic couplings has been attracting increasing interests from various research fields of neuroscience [6], [7]. A basic problem is how to detect the system structure from the neural activities.…”