cAMP evokes long-term facilitation in Aplysia sensory neurons that requires new protein synthesis

Science ◽  
1988 ◽  
Vol 240 (4859) ◽  
pp. 1667-1669 ◽  
Author(s):  
S Schacher ◽  
V. Castellucci ◽  
E. Kandel
Keyword(s):  
Protein Synthesis ◽  
Sensory Neurons ◽  
Long Term Facilitation ◽  
New Protein

5-HT modulates protein synthesis and the expression of specific proteins during long-term facilitation in aplysia sensory neurons

Neuron ◽  
1989 ◽  
Vol 2 (6) ◽  
pp. 1577-1586 ◽  
Author(s):  
A. Barzilai ◽  
T.E. Kennedy ◽  
J.D. Sweatt ◽  
E.R. Kandel
Keyword(s):  
Protein Synthesis ◽  
Sensory Neurons ◽  
Specific Proteins ◽  
Long Term Facilitation

scholarly journals Mammalian target of rapamycin is required for phrenic long-term facilitation following severe but not moderate acute intermittent hypoxia

2015 ◽  
Vol 114 (3) ◽  
pp. 1784-1791 ◽  
Author(s):  
Brendan J. Dougherty ◽  
Daryl P. Fields ◽  
Gordon S. Mitchell
Keyword(s):  
Protein Synthesis ◽  
Phrenic Nerve ◽  
Intermittent Hypoxia ◽  
Mammalian Target Of Rapamycin ◽  
Nerve Activity ◽  
Long Term Facilitation ◽  
New Protein ◽  
Mtor Activity ◽  
Dependent Mechanism

Phrenic long-term facilitation (pLTF) is a persistent increase in phrenic nerve activity after acute intermittent hypoxia (AIH). Distinct cell-signaling cascades give rise to pLTF depending on the severity of hypoxemia within hypoxic episodes. Moderate AIH (mAIH; three 5-min episodes, PaO2 ∼35–55 mmHG) elicits pLTF by a serotonin (5-HT)-dependent mechanism that requires new synthesis of brain-derived neurotrophic factor (BDNF), activation of its high-affinity receptor (TrkB), and ERK MAPK signaling. In contrast, severe AIH (sAIH; three 5-min episodes, PaO2 ∼25–30 mmHG) elicits pLTF by an adenosine-dependent mechanism that requires new TrkB synthesis and Akt signaling. Although both mechanisms require spinal protein synthesis, the newly synthesized proteins are distinct, as are the neurochemicals inducing plasticity (serotonin vs. adenosine). In many forms of neuroplasticity, new protein synthesis requires translational regulation via mammalian target of rapamycin (mTOR) signaling. Since Akt regulates mTOR activity, we hypothesized that mTOR activity is necessary for sAIH- but not mAIH-induced pLTF. Phrenic nerve activity in anesthetized, paralyzed, and ventilated rats was recorded before, during, and 60 min after mAIH or sAIH. Rats were pretreated with intrathecal injections of 20% DMSO (vehicle controls) or rapamycin (0.1 mM, 12 μl), a selective mTOR complex 1 inhibitor. Consistent with our hypothesis, rapamycin blocked sAIH- but not mAIH-induced pLTF. Thus spinal mTOR activity is required for adenosine-dependent (sAIH) but not serotonin-dependent (mAIH) pLTF, suggesting that distinct mechanisms regulate new protein synthesis in these forms of spinal neuroplasticity.

scholarly journals Induction of long-term facilitation in Aplysia sensory neurons by local application of serotonin to remote synapses

1993 ◽  
Vol 90 (23) ◽  
pp. 11411-11415 ◽  
Author(s):  
G A Clark ◽  
E R Kandel
Keyword(s):  
Gene Expression ◽  
Sensory Neurons ◽  
Cell Body ◽  
Sensory Cells ◽  
Target Cells ◽  
Synaptic Terminals ◽  
Dissociated Cell Culture ◽  
Synaptic Changes ◽  
Long Term Facilitation

Long-term synaptic facilitation at the connections of Aplysia sensory neurons onto their target cells involves alterations in gene expression. How then are the relevant cellular signals for the induction and expression of long-term synaptic changes conveyed between the nucleus and remote synaptic terminals? We have explored this question using a set of remote, peripheral terminals of siphon sensory cells, which are approximately 3 cm from the sensory cell body in the abdominal ganglion. We found that these remote synapses, like the proximal synapses previously studied in dissociated cell culture, can exhibit long-term facilitation 24 hr after cell-wide serotonin application. Furthermore, serotonin applications restricted to the remote synaptic terminals nevertheless produced long-term facilitation, indicating that signals generated in synaptic regions can trigger the long-term process, perhaps via retrograde signals to the nucleus to modify gene expression, followed by anterograde signals back to the terminal. Serotonin applications restricted to the cell body and proximal synapses of the sensory neuron also produced long-term facilitation at remote synapses, although to a lesser extent, suggesting that long-term facilitation is expressed cell-wide, but that superimposed on this cell-wide facilitation there appears to be a component that is synapse-specific.

Mechanisms Involved in Persistent Facilitation of Neuromuscular Synapses in Aplysia

2002 ◽  
Vol 87 (4) ◽  
pp. 2018-2030 ◽  
Author(s):  
Lyle E. Fox ◽  
Philip E. Lloyd
Keyword(s):  
Motor Neurons ◽  
Neuromuscular Synapses ◽  
Camp Pathway ◽  
Kinase C ◽  
Withdrawal Reflexes ◽  
Central Synapses ◽  
Long Term Facilitation ◽  
Camp Levels ◽  
New Protein

Synaptic plasticity can last from a fraction of a second to weeks depending on how it was induced. The mechanisms that underlie short-, intermediate-, and long-term plasticity have been intensively studied at central synapses of both vertebrates and invertebrates; however, peripheral plasticity has not received as much attention. In this study, we investigated the mechanisms that contribute to a persistent form of plasticity at neuromuscular synapses in buccal muscle I3a of Aplysia.These synapses are reversibly facilitated by the small cardioactive peptide (SCP), a peptide cotransmitter that is intrinsic to the motor neurons, and persistently facilitated by serotonin (5HT) released from modulatory neurons that are extrinsic to the motor circuit. Many of the short-term effects of 5HT and SCP are mediated by the cAMP pathway, but little is known about the mechanisms that underlie persistent modulation. We were able to eliminate several possible mechanisms. One of these was the possibility that the apparent reversal of SCP's effects was due to desensitization of the SCP receptor. Superfusion for longer periods or with higher concentrations of SCP indicate that the SCP receptors do not desensitize. We also determined that new protein synthesis is not required for the persistent facilitation of EJPs. Another possibility was that 5HT was taken up and slowly re-released. Our results suggest that this mechanism is also unlikely. Activation of the cAMP pathway does not appear to mediate persistent effects; however, 5HT as well as SCP does cause persistent increases in cAMP levels that can prime I3a synapses and increase the effectiveness of activators of the cAMP pathway. Instead, the persistent effects of 5HT are mimicked by phorbol, suggesting that protein kinase C or an Aplysia homologue of unc13 may mediate these effects. These results, in combination with results from experiments on the sensory neurons that contribute to withdrawal reflexes in Aplysia, suggest that the mechanisms for intermediate- and long-term facilitation may reside in all of the synapses involved in the sensory to motor response reflex.

Protein synthesis at synapse versus cell body: Enhanced but transient expression of long-term facilitation at isolated synapses

2003 ◽  
Vol 56 (3) ◽  
pp. 275-286 ◽  
Author(s):  
Ke Liu ◽  
Jiang-Yuan Hu ◽  
Denong Wang ◽  
Samuel Schacher
Keyword(s):  
Protein Synthesis ◽  
Transient Expression ◽  
Cell Body ◽  
Long Term Facilitation

scholarly journals Synapse-Specific, Long-Term Facilitation of Aplysia Sensory to Motor Synapses: A Function for Local Protein Synthesis in Memory Storage

Cell ◽  
1997 ◽  
Vol 91 (7) ◽  
pp. 927-938 ◽  
Author(s):  
Kelsey C Martin ◽  
Andrea Casadio ◽  
Huixiang Zhu ◽  
Yaping E ◽  
Jack C Rose ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Memory Storage ◽  
Local Protein Synthesis ◽  
Long Term Facilitation ◽  
Local Protein

scholarly journals ApTrkl, a Trk-like Receptor, Mediates Serotonin- Dependent ERK Activation and Long-Term Facilitation in Aplysia Sensory Neurons

Neuron ◽  
2004 ◽  
Vol 44 (4) ◽  
pp. 715-728 ◽  
Author(s):  
Jake Ormond ◽  
Jonathan Hislop ◽  
Yali Zhao ◽  
Neil Webb ◽  
Francois Vaillaincourt ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Erk Activation ◽  
Long Term Facilitation
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