PKA-activated ApAF-ApC/EBP heterodimer is a key downstream effector of ApCREB and is necessary and sufficient for the consolidation of long-term facilitation.

Long-term memory requires transcriptional regulation by a combination of positive and negative transcription factors. Aplysia activating factor (ApAF) is known to be a positive transcription factor that forms heterodimers with ApC/EBP and ApCREB2. How these heterodimers are regulated and how they participate in the consolidation of long-term facilitation (LTF) has not, however, been characterized.

Regulation of ApC/EBP mRNA by the Aplysia AU-rich element-binding protein, ApELAV, and its effects on 5-hydroxytryptamine-induced long-term facilitation.

Aplysia CCAAT enhancer-binding protein (ApC/EBP), a key molecular switch in 5-hydroxytryptamine (5-HT)-induced long-term facilitation of Aplysia, is quickly and transiently expressed in response to a 5-HT stimulus, but the mechanism underlying this dynamic expression profile remains obscure. Here, we report that the dynamic expression of ApC/EBP during long-term facilitation is regulated at the post-transcriptional level by AU-rich element (ARE)-binding proteins. We found that the 3'UTR of ApC/EBP mRNA contains putative sequences for ARE, which is a representative post-transcriptional cis-acting regulatory element that modulates the stability and/or the translatability of a distinct subset of labile mRNAs.

A nucleolar protein ApLLP induces ApC/EBP expression required for long-term synaptic facilitation in aplysia neurons.

In Aplysia, long-term synaptic plasticity is induced by serotonin (5-HT) or neural activity and requires gene expression. Here, we demonstrate that ApLLP, a novel nucleolus protein, is critically involved in both long-term facilitation (LTF) and behavioral sensitization. Membrane depolarization induced ApLLP expression, which activated ApC/EBP expression through a direct binding to CRE.

An Aplysia type 4 phosphodiesterase homolog localizes at the presynaptic terminals of Aplysia neuron and regulates synaptic facilitation.

The cAMP-dependent signaling pathway is critically involved in memory-related synaptic plasticity. cAMP-specific type 4 phosphodiesterases (PDE4) play a role in this process by regulating the cAMP concentration. However, it is unclear how PDE4 is involved in regulating synaptic plasticity.

Two interdependent TRPV channel subunits, inactive and Nanchung, mediate hearing in Drosophila.

Hearing in Drosophila depends on the transduction of antennal vibration into receptor potentials by ciliated sensory neurons in Johnston's organ, the antennal chordotonal organ. We previously found that a Drosophila protein in the vanilloid receptor subfamily (TRPV) channel subunit, Nanchung (NAN), is localized to the chordotonal cilia and required to generate sound-evoked potentials (Kim et al., 2003).

Thiol oxidation-mediated cell death in Aplysia cultured sensory neurons.

Cellular thiol groups modulate various aspects of cellular function, including cell death. In this study, we found that a thiol oxidant, diamide, induced morphological changes such as cell swelling, membrane blebbing, and chromatin condensation in Aplysia cultured sensory neurons. Furthermore, diamide induced biphasic changes in the membrane potential, where hyperpolarization was followed by depolarization.

Impairment of a parabolic bursting rhythm by the ectopic expression of a small conductance Ca2+-activated K+ channel in Aplysia neuron R15.

The electrical properties of neurons are produced by the coordinated activity of ion channels. K+ channels play a key role in shaping action potentials and in determining neural firing patterns. Small conductance Ca2+-activated K+ (SK(Ca)) channels are involved in modulating the slow component of afterhyperpolarization (AHP).

Beta-amyloid peptide binding protein does not couple to G protein in a heterologous Xenopus expression system.

Alzheimer's disease is a neurodegenerative disorder related to the formation of protein aggregates. beta-Amyloid protein (A beta), generated by enzymatic cleavage of amyloid precursor protein (APP), can cause such aggregation, and these aggregates may cause neuronal cell death by inducing apoptosis. However, A beta-induced intracellular signaling pathways involved in the neuronal death are not well understood.

Identification of nuclear/nucleolar localization signal in Aplysia learning associated protein of slug with a molecular mass of 18 kDa homologous protein.

We isolated a learning associated protein of slug with a molecular mass of 18 kDa (LAPS18) homologue from the expressed sequence tag database of Aplysia kurodai and named it Aplysia LAPS18-like protein (ApLLP). ApLLP encodes 120 amino acids and has 57% identity with LAPS18. To examine the subcellular expression pattern of ApLLP we constructed an EGFP-tagged ApLLP fusion protein and overexpressed it in both Aplysia neurons and COS-7 cells.

Synaptic facilitation by ectopic octopamine and 5-HT receptors in Aplysia.

The cAMP pathway plays a critical role in synaptic plasticity. We assessed using the ectopic expression of octopamine (OA) receptor, the contribution of the cAMP pathway to short-term facilitation of sensory-motor synapses in Aplysia. When synaptic connections were depressed to 20-30% of their initial EPSP amplitude, the application of OA to sensory cells expressing OA receptor showed significant synaptic facilitation, but this was less than the synaptic facilitation shown by 5-HT treatment.

Hydrogen peroxide modulates K+ ion currents in cultured Aplysia sensory neurons.

Hydrogen peroxide (H(2)O(2)) causes oxidative stress and is considered a mediator of cell death in various organisms. Our previous studies showed that prolonged (>6 h) treatment of Aplysia sensory neurons with 1 mM H(2)O(2) produced hyperpolarization of the resting membrane potential, followed by apoptotic morphological changes. In this study, we examined the effect of H(2)O(2) on the membrane conductance of Aplysia sensory neurons.

Hydrogen peroxide-induced cell death in cultured Aplysia sensory neurons.

Widespread neuronal cell death occurs during normal development and as a result of pathological conditions in the nervous system of many organisms. In this study, we investigated the cytotoxicity induced by H(2)O(2) in Aplysia mechanosensory neurons, which serve as a useful model in the study of learning and memory. Treatment with hydrogen peroxide (10(-2)-10 mM) for 3 h produced a nuclear DNA breakage in Aplysia sensory neurons, as revealed by TdT-mediated dUTP nick end labeling (TUNEL) staining, in a dose-dependent manner.