Yasumasa Watanabe

Tricyclic antidepressants block NMDA receptor-mediated synaptic responses and induction of long-term potentiation in rat hippocampal slices

The effects of tricyclic antidepressants (imipramine, desipramine and amitriptyline) on the NMDA receptor-mediated synaptic responses and the induction of long-term potentiation were investigated in the CA1 region and the dentate gyrus of rat hippocampal slices. Both in the CA1 region and in the dentate gyrus, all three antidepressants (3 x 10(-5)M) did not affect the evoked potential in normal artificial cerebrospinal fluid (CSF) but inhibited the NMDA receptor-mediated epileptiform responses in Mg(2+)-free artificial CSF. Furthermore, all three agents blocked the induction of long-term potentiation in a concentration-dependent manner, both in the CA1 region and in the dentate gyrus. The concentrations which were effective in blocking the induction of long-term potentiation were consistent with those in inhibiting the NMDA receptor-mediated synaptic responses in Mg(2+)-free artificial CSF. These results suggest that tricyclic antidepressants block the induction of long-term potentiation by inhibitory actions on NMDA receptors.

Roles of GABAA, NMDA and muscarinic receptors in induction of long-term potentiation in the medial and lateral amygdala in vitro.

We have studied mechanisms underlying long-term potentiation (LTP) in the medial and lateral amygdala using in vitro slice preparations. In normal bathing medium, LTP was not induced by tetanic stimulation (100 pulses at 100 Hz). However, in the presence of a GABAA blocker, picrotoxin or bicuculline, LTP was reproducibly induced in both medial and lateral amygdala. In the medial amygdala, the LTP induced in the presence of picrotoxin was blocked by 2-amino-5-phosphonovalerate (APV), an NMDA receptor antagonist, and was significantly reduced by scopolamine, a muscarinic receptor antagonist. On the other hand, the LTP in the lateral amygdala was not affected by APV, but was significantly reduced by scopolamine. These results suggest that both NMDA receptors and muscarinic receptors are involved in the induction of medial amygdala LTP, while muscarinic receptors, but not NMDA receptors, are involved in the induction of lateral amygdala LTP.

Involvement of glycine site associated with the NMDA receptor in hippocampal long-term potentiation and acquisition of spatial memory in rats.

The effects of 7-chlorokynurenic acid (7-Cl-Kyn), a selective antagonist at the glycine site associated with the N-methyl-D-aspartate (NMDA) receptor, on hippocampal long-term potentiation (LTP) and behavioral performances in a spatial learning task were investigated. Extracellular recordings of evoked potential (population spike) were made in rat hippocampal slices. Perfusion of 7-Cl-Kyn (10(-5) M) inhibited the induction of LTP following a tetanic stimulation (51 or 101 pulses at 100 Hz) both in the Schaffer/commissural-CA1 pyramidal cell synapses and in the perforant path-dentate granule cell synapses. Acquisition of a spatial memory in the Morris water maze was examined using rats chronically cannulated for application of drugs. The intact and vehicle-injected rats learned easily to escape onto a hidden platform with short latencies, while the rats given an injection of 7-Cl-Kyn (10(-8) mol/brain, i.c.v.) prior to every session took a longer time and a longer path to escape even after all 5 sessions of trials. Injection of 7-Cl-Kyn did not affect the swimming speed, an index of swimming ability. This is the first report providing direct evidence that endogenous glycine supports the processes of learning and memory.

Effects of glycine and structurally related amino acids on generation of long-term potentiation in rat hippocampal slices

The effects of glycine and structurally related amino acids, serine, alanine and valine, on generation of long-term potentiation (LTP) of evoked potentials were investigated in the CA1, CA3 and dentate regions of rat hippocampal slices. In the Schaffer collateral-CA1 pyramidal cell synapses and in the perforant path-dentate granule cell synapses, glycine (5 x 10(-4) M) significantly enhanced the short-term potentiation (STP) induced by subthreshold tetanic stimulation, without affecting baseline responses. The effects of glycine resulted in generation of LTP in both synapses. On the other hand, glycine did not influence STP induced by subthreshold tetanus in the mossy fiber-CA3 pyramidal cell synapses. These results suggest that exogenous glycine can facilitate the generation of LTP in the CA1 region and in the dentate gyrus but not in the CA3 region. In the CA1 region and the dentate gyrus, D- and L-serine and D-alanine (10(-3) M) also showed the LTP-facilitating effects in a similar manner to glycine, but D- and L-valine had no effect on LTP generation. Furthermore, glycine and D-serine, but not L-valine, enhanced NMDA receptor-mediated synaptic responses in the absence of extracellular Mg2+. Together, these results make it probable that exogenously applied glycine and related amino acids facilitate the generation of LTP in the CA1 and dentate region by activating the glycine modulatory sites associated with NMDA receptors.

Nitric oxide is involved in long-term potentiation in the medial but not lateral amygdala neuron synapses in vitro

Possible involvement of nitric oxide (NO) in the induction of long-term potentiation (LTP) in the amygdala was investigated using rat brain slice preparations in vitro. The induction of LTP in the medial amygdala was blocked by NO synthase inhibitors, NG-nitro-L-arginine and NG-nitro-L-arginine methyl ester, and an NO scavenger hemoglobin. On the other hand, the lateral amygdala LTP was not blocked by inhibition of endogenous NO. These results suggest that endogenous NO is involved in the induction of LTP in the medial amygdala but not in the lateral amygdala.

Glycine facilitates induction of long-term potentiation of evoked potential in rat hippocampus

Effects of glycine were investigated in Schaffer/commissural-CA1 pyramidal cell synapses of the rat hippocampal slices. Perfusion of glycine (0.05 mM) did not change baseline population spikes evoked by test stimulation but significantly enhanced short-term potentiation induced by a single shorter tetanus (100 Hz, 11 impulses); the effects resulted in production of long-term potentiation (LTP). LTP produced by a longer tetanus (100 Hz, 100 impulses, 2 trains) was not significantly influenced. Higher concentration (0.5 mM) of glycine increased the baseline spike amplitude. All these effects of glycine were not observed in the presence of 10(-5) M 2-amino-5-phosphonovalerate, an N-methyl-D-aspartate (NMDA) antagonist. These results demonstrate that glycine can facilitate induction of LTP probably by activating NMDA receptor.

Differential role of nitric oxide in long-term potentiation in the medial and lateral amygdala

The effects of nitric oxide (NO) donors on the induction of long-term potentiation in the amygdala were investigated using rat brain slice preparations in vitro. In the medial amygdala synapses, sodium nitroprusside (10 microM) and hydroxylamine (100 microM), when applied together with a weak tetanic stimulation, significantly facilitated the induction of long-term potentiation. The NO donors showed no effect in the lateral amygdala synapses. These results suggest that NO plays a role in facilitating the induction of long-term potentiation in the medial amygdala but not in the lateral amygdala.

Effects of Plasma Discharge on Hypersonic Flow over Flat Plate

As a preliminary study on the application of plasma discharge to hypersonic aerodynamic control, the effect of direct current (DC) plasma in a hypersonic flow was examined with wind tunnel experiments. It was shown that the pressure rises significantly in the upstream region of the discharge. To the contrary, the pressure decreases in the region very close to the electrodes. This pressure change would be applied to a new aerodynamic control device. Under the assumption that the effects of the plasma discharge in a hypersonic flow are mainly due to the Joule heating, three-dimensional Navier-Stokes analyses were conducted. It was concluded that the pressure change far from the plasma area can be explained as an effect of the heat addition to the flow.

Global stability analysis method to numerically predict precursor of breakdown voltage

This study presents a new method for predicting a precursor of breakdown voltage. This method applies a global linear stability analysis to a drift-diffusion model coupled with the Poisson equation. The instability of the solution of these equations is evaluated with the proposed method and is considered to be the onset of a breakdown. The proposed method is validated in one dimension by using the Townsend theory as a reference. To extend the one-dimensional case and investigate the characteristics of multidimensional eigenmodes, we apply the method to two-dimensional plane-to-plane discharge tubes. To prove an adaptability against complex electrodes geometry, the discharge path and the corresponding breakdown voltage for the well-known corner-to-plane geometry are qualitatively evaluated.

Effect of Impulsive Plasma Discharge in Hypersonic Boundary Layer over Flat Plate

The application of plasma discharge to hypersonic flow control methods has received a good deal of research attention in recent years. As a fundamental study for such methods, direct current plasma discharge in Mach-7 hypersonic flow over flat plate was investigated both with wind tunnel experiments and numerical analyses. Impulsive discharge in a boundary layer over flat plate caused a decrease in the wall pressure around electrodes. For the purpose of clarifying the principal cause of this phenomenon, a numerical analysis was conducted by solving the three-dimensional Navier-Stokes equations with impulsive energy addition to the flow. Numerical results revealed that the pressure oscillates in the vicinity of heated region, which suggests that the fluctuation of surface pressure observed in the experiment could be qualitatively explained as the unsteady response of the flow to the impulsive Joule heating by the discharge.