A novel form of presynaptic CaMKII-dependent short-term potentiation between Lymnaea neurons.

Short-term plasticity is thought to form the basis for working memory, the cellular mechanisms of which are the least understood in the nervous system. In this study, using in vitro reconstructed synapses between the identified Lymnaea neuron visceral dorsal 4 (VD4) and left pedal dorsal 1 (LPeD1), we demonstrate a novel form of short-term potentiation (STP) which is 'use'- but not time-dependent, unlike most previously defined forms of short-term synaptic plasticity. Using a triple-cell configuration we demonstrate for the first time that a single presynaptic neuron can reliably potentiate both inhibitory and excitatory synapses. We further demonstrate that, unlike previously described forms of STP, the synaptic potentiation between Lymnaea neurons does not involve postsynaptic receptor sensitization or presynaptic residual calcium. Finally, we provide evidence that STP at the VD4-LPeD1 synapse requires presynaptic calcium/calmodulin dependent kinase II (CaMKII). Taken together, our study identifies a novel form of STP which may provide the basis for both short- and long-term potentiation, in the absence of any protein synthesis-dependent steps, and involve CaMKII activity exclusively in the presynaptic cell.

Comparisons of two different doses of fentanyl for procedural analgesia during epidural catheter placement: a double-blind prospective, randomized, placebo-controlled study.

The purpose of this study was to investigate the effect of fentanyl on analgesic properties and respiratory responses during an epidural procedure. Sixty patients premedicated with oral brotizolam 0.25 mg were allocated to receive procedural analgesia with saline or 25 or 50 µg of fentanyl. Five minutes after administration, an epidural procedure was started. Pain assessments were made immediately after the epidural catheter placement using a visual analog scale. The lowest SpO2 levels during the procedure were recorded to evaluate respiratory depression, and cardiovascular complications were also recorded. The pain scores were significantly lower in the 25 and 50 µg fentanyl groups than in the placebo group (P < 0.01). There was no difference in pain assessment between the 25 and 50 µg fentanyl groups. The lowest SpO2 value of the 50 µg fentanyl group was significantly lower than those of the other groups (P < 0.001). Seven of 20 cases in the 50 µg fentanyl group needed oxygen administration because of a decreased SpO2 value (<94%). No cardiovascular complications were observed in any group during the entire study period. Thus, intravenous fentanyl at a dose of 25 µg provides effective procedural analgesia without the risk of hypoxemia during an epidural procedure in a patient with preanesthetic medication.

Sevoflurane blocks cholinergic synaptic transmission postsynaptically but does not affect short-term potentiation.

BACKGROUND: As compared with their effects on both inhibitory and excitatory synapses, little is known about the mechanisms by which general anesthetics affect synaptic plasticity that forms the basis for learning and memory at the cellular level. To test whether clinically relevant concentrations of sevoflurane affect short-term potentiation involving cholinergic synaptic transmission, the soma-soma synapses between identified, postsynaptic neurons were used. METHODS: Uniquely identifiable neurons visceral dorsal 4 (presynaptic) and left pedal dorsal 1 (postsynaptic) of the mollusk Lymnaea stagnalis were isolated from the intact ganglion and paired overnight in a soma-soma configuration. Simultaneous intracellular recordings coupled with fluorescent imaging of the FM1-43 dye were made in either the absence or the presence of sevoflurane. RESULTS: Cholinergic synapses, similar to those observed in vivo, developed between the neurons, and the synaptic transmission exhibited classic short-term, posttetanic potentiation. Action potential-induced (visceral dorsal 4), 1:1 excitatory postsynaptic potentials were reversibly and significantly suppressed by sevoflurane in a concentration-dependent manner. Fluorescent imaging with the dye FM1-43 revealed that sevoflurane did not affect presynaptic exocytosis or endocytosis; instead, postsynaptic nicotinic acetylcholine receptors were blocked in a concentration-dependent manner. To test the hypothesis that sevoflurane affects short-term potentiation, a posttetanic potentiation paradigm was used, and synaptic transmission was examined in either the presence or the absence of sevoflurane. Although 1.5% sevoflurane significantly reduced synaptic transmission between the paired cells, it did not affect the formation or retention of posttetanic potentiation at this synapse. CONCLUSIONS: This study demonstrates that sevoflurane blocks cholinergic synaptic transmission postsynaptically but does not affect short-term synaptic plasticity at the visceral dorsal 4-left pedal dorsal 1 synapse.

Anesthetic treatment blocks synaptogenesis but not neuronal regeneration of cultured Lymnaea neurons.

Trauma and injury necessitate the use of various surgical interventions, yet such procedures themselves are invasive and often interrupt synaptic communications in the nervous system. Because anesthesia is required during surgery, it is important to determine whether long-term exposure of injured nervous tissue to anesthetics is detrimental to regeneration of neuronal processes and synaptic connections. In this study, using identified molluscan neurons, we provide direct evidence that the anesthetic propofol blocks cholinergic synaptic transmission between soma-soma paired Lymnaea neurons in a dose-dependent and reversible manner. These effects do not involve presynaptic secretory machinery, but rather postsynaptic acetylcholine receptors were affected by the anesthetic. Moreover, we discovered that long-term (18-24 h) anesthetic treatment of soma-soma paired neurons blocked synaptogenesis between these cells. However, after several hours of anesthetic washout, synapses developed between the neurons in a manner similar to that seen in vivo. Long-term anesthetic treatment of the identified neurons visceral dorsal 4 (VD4) and left pedal dorsal 1 (LPeD1) and the electrically coupled Pedal A cluster neurons (PeA) did not affect nerve regeneration in cell culture as the neurons continued to exhibit extensive neurite outgrowth. However, these sprouted neurons failed to develop chemical (VD4 and LPeD1) and electrical (PeA) synapses as observed in their control counterparts. After drug washout, appropriate synapses did reform between the cells, although this synaptogenesis required several days. Taken together, this study provides the first direct evidence that the clinically used anesthetic propofol does not affect nerve regeneration. However, the formation of both chemical and electrical synapses is severely compromised in the presence of this drug. This study emphasizes the importance of short-term anesthetic treatment, which may be critical for the restoration of synaptic connections between injured neurons.