Long-term regulation of neuronal high-affinity glutamate and glutamine uptake in Aplysia

Abstract

An increase in transmitter release accompanying long-term sensitization and facilitation occurs at the glutamatergic sensorimotor synapse of Aplysia. We report that a long-term increase in neuronal Glu uptake also accompanies long-term sensitization. Synaptosomes from pleural-pedal ganglia exhibited sodium-dependent, high-affinity Glu transport. Different treatments that induce longterm enhancement of the siphon-withdrawal reflex, or long-term synaptic facilitation increased Glu uptake. Moreover, 5-hydroxytryptamine, a treatment that induces long-term facilitation, also produced a long-term increase in Glu uptake in cultures of sensory neurons. The mechanism for the increase in uptake is an increase in the V max of transport. The long-term increase in Glu uptake appeared to be dependent on mRNA and protein synthesis, and transport through the Golgi, because 5,6-dichlorobenzimidazole riboside, emetine, and brefeldin A inhibited the increase in Glu uptake. Also, injection of emetine and 5,6-dichlorobenzimidazole into Aplysia prevented long-term sensitization. Synthesis of Glu itself may be regulated during long-term sensitization because the same treatments that produced an increase in Glu uptake also produced a parallel increase in Gln uptake. These results suggest that coordinated regulation of a number of different processes may be required to establish or maintain long-term synaptic facilitation.

Different Mechanisms Exist for the Plasticity of Glutamate Reuptake during Early Long-Term Potentiation (LTP) and Late LTP

“…For example, in both vertebrates and invertebrates, changes in glutamate uptake parallel changes in synaptic efficacy (Levenson et al, 2000(Levenson et al, , 2002. In addition, changes in synaptic efficacy produced by morphine withdrawal were associated with increases in glutamate uptake in synaptosomes obtained from hippocampus (Xu et al, 2003).…”

Interaction between Amount and Pattern of Training in the Induction of Intermediate- and Long-Term Memory for Sensitization in Aplysia

“…Whereas a single tail shock induces short-term memory (STM) for sensitization lasting minutes, repeated spaced shocks produce LTM for sensitization lasting days to weeks (Frost et al 1985;Scholz and Byrne 1987;Castellucci et al 1989;Goldsmith and Byrne 1993;Cleary et al 1998;Levenson et al 2000;Sutton et al 2001a;see also, Carew et al 1971;Pinsker et al 1973). Recently, we distinguished a third phase of memory for sensitization, intermediate-term memory (ITM), that is induced by repeated spaced shocks and lasts 1-3 h after training (Sutton et al 2001a).…”

“…Recently, we distinguished a third phase of memory for sensitization, intermediate-term memory (ITM), that is induced by repeated spaced shocks and lasts 1-3 h after training (Sutton et al 2001a). These three phases of memory for sensitization in Aplysia can be mechanistically distinguished in a similar fashion as their synaptic counterparts: STM requires neither protein nor RNA synthesis, ITM requires protein but not RNA synthesis, and LTM requires both (Castellucci et al 1989;Levenson et al 2000;Sutton et al 2001a). ITM and LTM can also be distinguished in the same animals based on the temporal dynamics of memory for sensitization after training: five spaced tail shocks induces ITM that decays completely to baseline by about 3 h, several hours before the emergence of LTM (Sutton et al 2001a).…”

Modulation of EAAC1-Mediated Glutamate Uptake by Addicsin

“…These results indicate that EAAC1 functions as a cysteine transporter in neurons and sustains intracellular GSH to ameliorate oxidative stress in vivo. Furthermore, neuronal glutamate uptake can also regulate memory formation (Levenson et al, 2000;Maleszka et al, 2000). The increase of EAAC1-mediated neuronal glutamate uptake is associated with the induction and expression of early phase long-term potentiation (LTP) in the CA1 area of the hippocampal formation and with contextual fear conditioning, a form of hippocampus-dependent memory thought to depend on induction of LTP (Levenson et al, 2002).…”