Voltage-Gated ion currents of schwann cells in cell culture models of human neurofibromatosis

K(+) (K) channels play a role in the proliferation of many cell types in normal cells and certain disease states. Several laboratories have studied K currents in cultured Schwann cells from models of the human diseases, neurofibromatosis type 1 (NF1) and neurofibromatosis type 2 (NF2). These diseases are characterized by the growth of Schwann cell tumors. In all cell culture NF models the K current properties differ in tumor-derived and normal Schwann cells. Depending on the model however, the type of K channel abnormality differs. K channels appear to play a role in the proliferation of Schwann cell cultures of these disease models, because a link has been established between K current blockade and the inhibition of Schwann cell proliferation in NF1 and NF2. Differences in the proliferation response of normal Schwann cells to K channel blockers suggest that in vitro regulation of proliferation in neoplastic and normal Schwann cells is complex

Neurotransmitters and Neuropeptides of Invertebrates

This chapter introduces working definitions of neuropeptides and neurotransmitters from the perspective of invertebrate physiological processes. Neuropeptides and neurotransmitters are intercellular chemical signaling agents used by all animals. Chemical signaling augments or substitutes for electrical communication in the nervous system. When these agents act as neurotransmitters, they convert electrical signals to chemical signals across the synapse. As hormones, they circulate from a site of release to act at a more distant site in the body of the organism. Neuropeptides and neurotransmitters are classified into these groups mostly on the basis of their molecular size. This article describes several neuropeptide superfamilies and their wide scope of actions in model invertebrates. The article also describes the main neurotransmitters used by invertebrates

The development of excitatory capability in Aplysia californica bag cells observed in cohorts

The bag cells of Aplysia release egg laying hormone in sexually mature animals. Bag cells cannot sustain the long-lasting excitatory afterdischarge (AD) required for hormone release prior to sexual maturity (T.A. Nick, L.K. Kaczmarek, T.J. Carew, Ionic currents underlying developmental regulation of repetitive firing in Aplysia bag cell neurons, J. Neurosci. 1996;16:7583–7598; L.A. Fieber, Characterization of Na + and Ca 2+ currents in bag cells of sexually immature Aplysia californica, J. Exp. Biol. 1998;201:745–754). To investigate the development of bag cell excitability, whole-cell voltage-clamp experiments were executed in dissociated bag cells from four cohorts (batches) of hatchery-reared A. californica maintained at 13–15°C. K + current densities, representing the sum of at least four different outward K + currents (Nick et al., 1996), declined significantly as a function of age, beginning at least 2–3 months before sexual maturity. The K + current decreases coincided with the first appearance of Na + and Ca 2+ currents in bag cells, which occurred at ages 6–7 months. Whole cell K + currents were not decreased significantly by a cAMP analog earlier than 1 month prior to the onset of reproductive activity. The frequency of observing Na + currents in whole cell recordings was low for developmental times earlier than sexual maturity. In one winter batch, both control and PMA-treated Na + currents increased significantly with age, and PMA-treated current densities were significantly greater than controls, but the other two batches studied had significant differences in Na + current frequency only at sexual maturity. Ca 2+ currents were reliably measured in more cells than were Na + currents. The Ca 2+ current frequency increased significantly with maturity in one winter batch. Ca 2+ currents were significantly increased by phorbol ester treatment beginning 6–8 weeks before reproductive activity in the two winter batches. These observations support the hypothesis that bag cell excitability is not fully developed until shortly before sexual maturity

Life history and aging of captive-reared California sea hares (Aplysia californica)

Although the California sea hare, Aplysia californica, is well known from neurobiological studies and is raised in the laboratory for this purpose, various aspects of its life history in the laboratory, such as aging dynamics, are unknown. Therefore we collected life history data on 4 cohorts of eggs from hatchery-reared animals and performed an actuarial analysis of mortality data. Temperature was controlled at 13 to 15 degrees C, the photoperiod was a 14:10-h light:dark cycle, and the seawater O2 concentration, pH, and salinity were held at optimized levels. The feeding protocol for 3 cohorts was unrestricted access to the red macroalga Gracilaria ferox, whereas the remaining cohort was fed standard hatchery rations of G. ferox 4 times per week. Growth was sigmoidal in each cohort and resulted in linear growth rates of 1.25 to 3.62 g/d during the exponential phase; these rates were not influenced by feeding level. Sexual maturity occurred at approximately 160 g, at ages ranging from 144 to 241 d. Egg production was highly variable in the different cohorts. Mean lifespan of cohorts fed ad libitum was approximately 228 d. In contrast, the cohort fed standard rations lived an average of 375 d and showed a lower initial mortality rate, suggesting that calorie restriction on a single-species diet prolongs lifespan in California sea hares

Aging in Sensory and Motor Neurons Results in Learning Failure in Aplysia californica

The physiological and molecular mechanisms of age-related memory loss are complicated by the complexity of vertebrate nervous systems. This study takes advantage of a simple neural model to investigate nervous system aging, focusing on changes in learning and memory in the form of behavioral sensitization in vivo and synaptic facilitation in vitro. The effect of aging on the tail withdrawal reflex (TWR) was studied in Aplysia californica at maturity and late in the annual lifecycle. We found that short-term sensitization in TWR was absent in aged Aplysia. This implied that the neuronal machinery governing nonassociative learning was compromised during aging. Synaptic plasticity in the form of short-term facilitation between tail sensory and motor neurons decreased during aging whether the sensitizing stimulus was tail shock or the heterosynaptic modulator serotonin (5-HT). Together, these results suggest that the cellular mechanisms governing behavioral sensitization are compromised during aging, thereby nearly eliminating sensitization in aged Aplysia

Improvements in operant memory of Aplysia are correlated with age and specific gene expression

The transcription factor Aplysia CCAAT/enhancer binding protein ( ApC/EBP ) is expressed as an immediate early gene in the cAMP responsive element binding protein (CREB) mediated gene cascade, and it has essential functions in the synaptic consolidation of memory following a learning event. Synaptic consolidation primarily involves morphological changes at neuronal synapses, which are facilitated through the reorganization of the actin and microtubular cytoarchitecture of the cell. During early nervous system development, the transmembrane synaptic protein teneurin acts directly upon neuronal presynaptic microtubules and postsynaptic spectrin-based cytoskeletons to facilitate the creation of new synapses. It is reasonable to hypothesize that teneurin may also be linked to learning-induced synaptic changes and is a potential candidate to be a later gene expressed in the CREB-mediated gene cascade downstream of ApC/EBP . To assess the role of ApC/EBP and teneurin in learning and memory in the marine snail Aplysia californica , young (age 7–8 months) and aged (age 13–15 months; aging stage AII) siblings of Aplysia were trained in an operant conditioning paradigm—learning food is inedible (LFI)—over 2 days, during which they learned to modify the feeding reflex. Aged Aplysia had enhanced performance of the LFI task on the second day than younger siblings although far more aged animals were excluded from the analysis because of the initial failure in learning to recognize the inedible probe. After 2 days of training, ApC/EBP isoform X1 mRNA and teneurin mRNA were quantified in selected neurons of the buccal ganglia, the locus of neural circuits in LFI. Teneurin expression was elevated in aged Aplysia compared to young siblings regardless of training. ApC/EBP isoform X1 expression was significantly higher in untrained aged animals than in untrained young siblings but decreased in trained aged animals compared to untrained aged animals. Elevated levels of ApC/EBP isoform X1 and teneurin mRNA before training may have contributed to the enhancement of LFI performance in the aged animals that successfully learned

Unique ionotropic receptors for D-aspartate are a target for serotonin-induced synaptic plasticity in Aplysia californica

The non- l-glutamate ( l-Glu) receptor component of d-aspartate ( d-Asp) currents in Aplysia californica buccal S cluster (BSC) neurons was studied with whole cell voltage clamp to differentiate it from receptors activated by other well-known agonists of the Aplysia nervous system and investigate modulatory mechanisms of d-Asp currents associated with synaptic plasticity. Acetylcholine (ACh) and serotonin (5-HT) activated whole cell excitatory currents with similar current voltage relationships to d-Asp. These currents, however, were pharmacologically distinct from d-Asp. ACh currents were blocked by hexamethonium (C6) and tubocurarine (d-TC), while d-Asp currents were unaffected. 5-HT currents were blocked by granisetron and methysergide (MES), while d-Asp currents were unaffected. Conversely, while (2S,3R)-1-(Phenanthren-2-carbonyl)piperazine-2,3-dicarboxylic acid(PPDA) blocked d-Asp currents, it had no effect on ACh or 5-HT currents. Comparison of the charge area described by currents induced by ACh or 5-HT separately from, or with, d-Asp suggests activation of distinct receptors by all 3 agonists. Charge area comparisons with l-Glu, however, suggested some overlap between l-Glu and d-Asp receptors. Ten minute exposure to 5-HT induced facilitation of d-Asp-evoked responses in BSC neurons. This effect was mimicked by phorbol ester, suggesting that protein kinase C (PKC) was involved