Roles of PKA and PKC in facilitation of evoked and spontaneous transmitter release at depressed and nondepressed synapses in aplysia sensory neurons (original) (raw)
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Modulation of a cAMP/protein kinase A cascade by protein kinase C in sensory neurons of Aplysia
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1997
The synaptic connections between the sensory neurons of Aplysia and their follower neurons have been used as a model system for examining the cellular mechanisms contributing to neuronal and synaptic plasticity. Recent studies suggest that at least two protein kinases, protein kinase A (PKA) and protein kinase C (PKC), contribute to serotonin (5-HT)-induced short-term facilitation. The interaction between these two kinase cascades has not been examined, however. Using electrophysiological and biochemical approaches, we examined possible interactions between PKA and PKC cascades. The results indicated that prolonged activation of PKC by preincubation with phorbol esters attenuated PKA-mediated actions of 5-HT, including increases in sensory neuron excitability and spike broadening in the presence of tetraethylammonium (TEA) and nifedipine. Although phorbol esters also attenuated increases in excitability by an analog of cAMP and small cardioactive peptide B (SCPB), the degree of atte...
Proceedings of the National Academy of Sciences, 1998
Long-term facilitation of the connections between the sensory and motor neurons of the gill-withdrawal ref lex in Aplysia requires five repeated pulses of serotonin (5-HT). The repeated pulses of 5-HT initiate a cascade of gene activation that leads ultimately to the growth of new synaptic connections. Several genes in this process have been identified, including the transcriptional regulators apCREB-1, apCREB-2, apC͞EBP, and the cell adhesion molecule ap-CAM, which is thought to be involved in the formation of new synaptic connections. Here we report that the transcriptional regulators apCREB-2 and apC͞EBP, as well as a peptide derived from the cytoplasmic domain of apCAM, are phosphorylated in vitro by Aplysia mitogen-activated protein kinase (apMAPK). We have cloned the cDNA encoding apMAPK and show that apMAPK activity is increased in sensory neurons treated with repeated pulses of 5-HT and by the cAMP pathway. These results suggest that apMAPK may participate with cAMP-dependent protein kinase during long-term facilitation in sensory cells by modifying some of the key elements involved in the consolidation of short-to long-lasting changes in synaptic strength.
Proceedings of the National Academy of Sciences, 1984
We have found that two endogenous neuropeptides in Aplysia, the small cardioactive peptides SCPA and SCPB, facilitate synaptic transmission from siphon mechano-sensory neurons and enhance the defensive withdrawal reflex that these sensory neurons mediate. Single-channel recording revealed that these peptides close a specific K+ channel, the S channel, which is sensitive to cAMP. Moreover, the peptides increase cAMP levels in these sensory neurons. This reduction in K+ current slows the repolarization of the action potential in these cells, which increases transmitter release. In these actions, the SCPs resemble both noxious sensitizing stimuli, which enhance the reflex, and serotonin. Bioassay of HPLC fractions of abdominal ganglion extracts and immunocytochemistry indicate that both the SCPs and serotonin are present in the ganglion and are found in processes close to the siphon sensory neurons, suggesting that these transmitters may be involved in behavioral sensitization. Recent ...
Neuroscience, 2003
Activation of the extracellular signal-related kinase is important for long-term increases in synaptic strength in the Aplysia nervous system. However, there is little known about the mechanism for the activation of the kinase in this system. We examined the activation of Aplysia extracellular signal-related kinase using a phosphopeptide antibody specific to the sites required for activation of the kinase. We found that phorbol esters led to a prolonged activation of extracellular signal-related kinase in sensory cells of the Aplysia nervous system. Surprisingly, inhibitors of protein kinase C did not block this activation. Serotonin, the physiological transmitter involved in long-term synaptic facilitation, also led to prolonged activation of extracellular signal-related kinase, but inhibitors of protein kinase A or protein kinase C did not block this activation. We examined whether the protein synthesis-dependent increase in excitability stimulated by phorbol esters was dependent on phorbol ester activation of extracellular signal-related kinase, but increases in excitability were still seen in the presence of inhibitors of extracellular signal-related kinase activation. Our results suggest that prolonged phosphorylation of extracellular signal-related kinase in the Aplysia system is not mediated by either of the classic second messenger activated kinases in this system, protein kinase A or protein kinase C and that extracellular signal-related kinase is not important for phorbol ester induced long-term effects on excitability.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2001
At nondepressed Aplysia sensory to motor synapses, serotonin (5-HT) facilitates transmitter release primarily through a protein kinase A pathway. In contrast, at depressed Aplysia sensory to motor synapses, 5-HT facilitates transmitter release primarily through a protein kinase C (PKC)-dependent pathway. It is known that only two phorbol ester-activated PKC isoforms, the Ca(2+)-dependent PKC Apl I and the Ca(2+)-independent PKC Apl II, exist in the Aplysia nervous system. For the first time, we have now been able to functionally determine which isoform of PKC is involved in a particular form of plasticity. We microinjected cultured sensorimotor pairs of neurons with various PKC constructs tagged with the enhanced green fluorescent protein as a reporter for successful plasmid expression. Our results demonstrate that short-term facilitation of depressed synapses is mediated by PKC Apl II. Dominant-negative PKC Apl II, but not dominant-negative PKC Apl I, disrupted the normal kinetics ...
Journal of Neuroscience, 2003
Short-term homosynaptic depression and heterosynaptic facilitation of transmitter release from mechanoreceptor sensory neurons of Aplysia are involved in habituation and sensitization, respectively, of defensive withdrawal reflexes. We investigated whether synaptic transmission is regulated in these forms of plasticity by means of changes in the size of the pool of transmitter available for immediate release [the readily releasable pool (RRP)] or in the efficacy of release from an unchanging pool. Using sensorimotor synapses formed in cell culture, we estimated the number of transmitter quanta in the RRP from the asynchronous release of neurotransmitter caused by application of a hypertonic bathing solution. Our experiments indicate that the transmitter released by action potentials and by hypertonic solution comes from the same pool. The RRP was reduced after homosynaptic depression of the EPSP by low-frequency stimulation and increased after facilitation of the EPSP by application of the endog-enous facilitatory transmitter serotonin (5-HT) after homosynaptic depression. However, although the fractional changes in the RRP and in the EPSP were similar for both synaptic depression and facilitation when depression was induced by repeated hypertonic stimulation, the changes in the EPSP were significantly greater than the changes in the RRP when depression was induced by repeated electrical stimulation. These observations indicate that homosynaptic depression and restoration of depressed transmission by 5-HT are caused by changes in both the amount of transmitter available for immediate release and in processes involved in the coupling of the action potential to transmitter release.