Relationship between increase in astrocytic GLT-1 glutamate transport and late-LTP.

Na⁺-dependent high-affinity glutamate transporters have important roles in the maintenance of basal levels of glutamate and clearance of glutamate during synaptic transmission. Interestingly, several studies have shown that basal glutamate transport displays plasticity. Glutamate uptake increases in hippocampal slices during early long-term potentiation (E-LTP) and late long-term potentiation (L-LTP).

Regulation of glutamate transporter GLT-1 by MAGI-1.

The sodium-dependent glutamate transporter, glutamate transporter subtype 1 (GLT-1) is one of the main glutamate transporters in the brain. GLT-1 contains a COOH-terminal sequence similar to one in an isoform of Slo1 K(+) channel protein previously shown to bind MAGI-1 (membrane-associated guanylate kinase with inverted orientation protein-1). MAGI-1 is a scaffold protein which allows the formation of complexes between certain transmembrane proteins, actin-binding proteins, and other regulatory proteins.

PKG-mediated MAPK signaling is necessary for long-term operant memory in Aplysia.

Signaling pathways necessary for memory formation, such as the mitogen-activated protein kinase (MAPK) pathway, appear highly conserved across species and paradigms. Learning that food is inedible (LFI) represents a robust form of associative, operant learning that induces short- (STM) and long-term memory (LTM) in Aplysia. We investigated the role of MAPK signaling in LFI memory in vivo.

Intermediate-term memory is modulated by the circadian clock.

Sensitization of the tail-siphon withdrawal reflex in Aplysia, a nonassociative form of learning, affords a superb opportunity to investigate the regulation of learning and memory by the circadian clock. The circadian clock has been shown to modulate long-term but not short-term sensitization. However, no previous studies have examined the role of the circadian clock in intermediate-term memory.

Post-translational regulation of an Aplysia glutamate transporter during long-term facilitation.

Regulation of glutamate transporters accompanies plasticity of some glutamatergic synapses. The regulation of glutamate uptake at the Aplysia sensorimotor synapse during long-term facilitation (LTF) was investigated. Previously, increases in levels of ApGT1 (Aplysia glutamate transporter 1) in synaptic membranes were found to be related to long-term increases in glutamate uptake.

Training with inedible food in Aplysia causes expression of C/EBP in the buccal but not cerebral ganglion.

Training with inedible food in Aplysia increased expression of the transcription factor C/EBP in the buccal ganglia, which primarily have a motor function, but not in the cerebral or pleural ganglia. C/EBP mRNA increased immediately after training, as well as 1-2 h later. The increased expression of C/EBP protein lagged the increase in mRNA.

In vivo regulation of an Aplysia glutamate transporter, ApGT1, during long-term memory formation.

Regulation of glutamate transporters often accompanies glutamatergic synaptic plasticity. We investigated the mechanisms responsible for the increase in glutamate uptake associated with increased glutamate release at the Aplysia sensorimotor synapse during long-term sensitization (LTS) and long-term facilitation. An increase in the V(max) of transport, produced by LTS training, suggested that the increased glutamate uptake was due to an increase in the number of transporters in the membrane.

Different mechanisms exist for the plasticity of glutamate reuptake during early long-term potentiation (LTP) and late LTP.

Regulation of glutamate reuptake occurs along with several forms of synaptic plasticity. These associations led to the hypothesis that regulation of glutamate uptake is a general component of plasticity at glutamatergic synapses. We tested this hypothesis by determining whether glutamate uptake is regulated during both the early phases (E-LTP) and late phases (L-LTP) of long-term potentiation (LTP).

The circadian clock modulates core steps in long-term memory formation in Aplysia.

The circadian clock modulates the induction of long-term sensitization (LTS) in Aplysia such that long-term memory formation is significantly suppressed when animals are trained at night. We investigated whether the circadian clock modulated core molecular processes necessary for memory formation in vivo by analyzing circadian regulation of basal and LTS-induced levels of phosphorylated mitogen-activated protein kinase (P-MAPK) and Aplysia CCAAT/enhancer binding protein (ApC/EBP). No basal circadian regulation occurred for P-MAPK or total MAPK in pleural ganglia.

Non-ocular circadian oscillators and photoreceptors modulate long term memory formation in Aplysia.

In Aplysia californica, memory formation for long-term sensitization (LTS) and for a more complex type of associative learning, learning that food is inedible (LFI), is modulated by a circadian clock. For both types of learning, formation of long-term memory occurs during the day and significantly less during the night. Aplysia eyes contain a well-characterized circadian oscillator that is strongly coupled to the locomotor activity rhythm.

TGF-beta1-induced long-term changes in neuronal excitability in aplysia sensory neurons depend on MAPK.

Transforming growth factor beta-1 (TGF-beta1) plays important roles in the early development of the nervous system and has been implicated in neuronal plasticity in adult organisms. It induces long-term increases in sensory neuron excitability in Aplysia as well as a long-term enhancement of synaptic efficacy at sensorimotor synapses. In addition, TGF-beta1 acutely regulates synapsin phosphorylation and reduces synaptic depression induced by low-frequency stimuli.

Circadian modulation of complex learning in diurnal and nocturnal Aplysia.

Understanding modulation of memory, as well as the mechanisms underlying memory formation, has become a key issue in neuroscience research. Previously, we found that the formation of long-term, but not short-term, memory for a nonassociative form of learning, sensitization, was modulated by the circadian clock in the diurnal Aplysia californica. To define the scope of circadian modulation of memory, we examined an associative operant learning paradigm, learning that food is inedible (LFI).

Coregulation of glutamate uptake and long-term sensitization in Aplysia.

In Aplysia, long-term facilitation (LTF) at sensorimotor synapses of the pleural-pedal ganglia is mediated by an increase in the release of a neurotransmitter, which appears to be glutamate. Glutamate uptake also is increased in sensory neurons 24 hr after the induction of long-term sensitization (Levenson et al., 2000b).

Circadian modulation of long-term sensitization in Aplysia.

As the mechanisms for learning and memory are elucidated, modulation of learning and memory becomes a central issue. We studied the modulation of learning and memory by investigating the circadian regulation of short- and long-term sensitization of the siphon withdrawal reflex in Aplysia. We found that Aplysia exhibited diurnal and circadian rhythms of long-term sensitization (LTS) with significantly greater LTS occurring when animals were trained and tested during the day relative to those trained and tested at night.

Desensitization of postsynaptic glutamate receptors contributes to high-frequency homosynaptic depression of aplysia sensorimotor connections.

Withdrawal reflexes of Aplysia are mediated in part by a monosynaptic circuit of sensory (SN) and motor (MN) neurons. A brief high-frequency burst of spikes in the SN produces excitatory postsynaptic potentials (EPSPs) that rapidly decrease in amplitude during the burst of activity. It is generally believed that this and other (i.

Circadian regulation of a transcription factor, ApC/EBP, in the eye of Aplysia californica.

The transcription factor, ApC/EBP (Aplysia CCAAT enhancer-binding protein) is an immediate early gene that is rapidly induced by serotonin and the cAMP signaling pathway. ApC/EBP acts as an important link following the activation of protein kinase A (PKA) in the consolidation of long-term memory in Aplysia californica. In this study, we report that levels of ApC/EBP mRNA in the eye of Aplysia are modulated by serotonin or light.

Glutamate uptake in synaptic plasticity: from mollusc to mammal.

A great deal of research has been directed toward understanding the cellular mechanisms underlying synaptic plasticity and memory formation. To this point, most research has focused on the more "active" components of synaptic transmission: presynaptic transmitter release and postsynaptic transmitter receptors. Little work has been done characterizing the role neurotransmitter transporters might play during changes in synaptic efficacy.

Inhibitor of glutamate transport alters synaptic transmission at sensorimotor synapses in Aplysia.

Aplysia sensory neurons possess high-affinity glutamate uptake activity that is regulated by serotonin. To gain insight into the physiological role of glutamate uptake in sensory neurons, we examined whether blockade of glutamate transport altered synaptic transmission. We also examined whether glutamate transport affected homosynaptic depression and posttetanic potentiation (PTP).

Long-term potentiation and contextual fear conditioning increase neuronal glutamate uptake.

Induction and expression of long-term potentiation (LTP) in area CA1 of the hippocampus require the coordinated regulation of several cellular processes. We found that LTP in area CA1 was associated with an N-methyl-D-aspartate (NMDA) receptor-dependent increase in glutamate uptake. The increase in glutamate uptake was inhibited by either removal of Na+ or addition of D,L-threo-beta-hydroxyaspartate.