Xiao Yan Han

Hippocampus in relation to mental sweating response evoked by memory recall and mental calculation: a human electroencephalography study with dipole tracing.

Mental-sweating response (MSR) was observed in the palm when the subject was asked to perform a mentally stressful task such as memory recall or mental calculation. About 4 s before the development of MSR, small MSR-related wavelets (MSR wavelets) and large waves were randomly generated on electroencephalograph. After differentiating the two types of waves, we calculated locations of the current dipole of MSR wavelets using the two-dipole model of the SSB/dipole tracing method. The result showed that one current dipole of MSR wavelets was consistently located in the hippocampus while the other dipole was widely dispersed in the cortex during memory recall and mental calculation.

Identifiable Achatina giant neurones: Their localizations in ganglia, axonal pathways and pharmacological features

1. An African giant snail (Achatina fulica Férussac), originally from East Africa, is now found abundantly in tropical and subtropical regions of Asia, including Okinawa in Japan. This is one of the largest land snail species in the world. The Achatina central nervous system is composed of the buccal, cerebral and suboesophageal ganglia. The 37 giant neurones were identified in these ganglia by the series of studies conducted over about 20 years. The identifications were made by the localization of these neurones in the ganglia, their axonal pathways and their pharmacological features. 2. In the left buccal ganglion, the four giant neurones, d-LBAN, d-LBMB, d-LBCN and d-LBPN, were identified. In the left and right cerebral ganglia, d-LCDN, d-RCDN, v-LCDN and v-RCDN were identified. The suboesophageal ganglia are further composed of the left and right parietal, the visceral, the left and right pleural, and the left and right pedal ganglia. In the right parietal ganglion, PON, TAN, TAN-2, TAN-3, RAPN, d-RPLN, BAPN, LPPN, LBPN, LAPN and v-RPLN were identified. In the visceral ganglion, VIN, FAN, INN, d-VLN, v-VLN, v-VAN, LVMN, RVMN and v-VNAN were identified. In the left parietal ganglion, v-LPSN was identified. In the left and right pedal ganglia, LPeNLN, RPeNLN, d-LPeLN, d-LPeCN, d-RPeAN, d-LPeDN, d-LPeMN and d-LPeEN were identified. 3. Of the small molecule compounds tested, dopamine, 5-hydroxytryptamine, GABA, L-glutamic acid, threo- or erythro-beta-hydroxy-L-glutamic acid were effective on the Achatina giant neurones. We suppose that these compounds act as the neurotransmitters for these neurones. 4. Of the neuroactive peptides, achatin-I(Gly-D-Phe-Ala-Asp). APGW-amide(Ala-Pro-Gly-Trp-NH2) and Achatina cardioexcitatory peptide (ACEP-1)(Ser-Gly-Gln-Ser-Trp-Arg-Pro-Gln-Gly-Arg-Phe-NH2) were proposed as neurotransmitters, because these were effective on the Achatina giant neurones and their presence was demonstrated in the Achatina ganglia. Further, myomodulin (Pro-Met-Ser-Met-Leu-Arg-Leu-NH2), buccalin (Gly-Met-Asp-Ser-Leu-Ala-Phe-Ser-Gly-Gly-Leu-NH2), FMRFamide (Phe-Met-Arg-Phe-NH2). [Ser2]-Mytilus inhibitory peptide ([Ser2]-MIP) (Gly-Ser-Pro-Met-Phe-Val-NH2), catch-relaxing peptide (CARP) (Ala-Met-Pro-Met-Leu-Arg-Leu-NH2), oxytocin (Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly-NH2) and small cardioactive peptideB (SCPB) (Met-Asn-Tyr-Leu-Ala-Phe-Pro-Arg-Met-NH2) could also be neurotransmitters because these peptides were also effective on the Achatina giant neurones, though their presence in the ganglia of this animal has not yet been demonstrated. 5. Calcium current (ICa) was recorded from Achatina giant neurones in the Na(+)-free solution containing K(+)-channel blockers under voltage clamp. The Ca2+ antagonistic effects of brovincamine, verapamil, eperisone, diltiazem, monatepil, etc., were compared using the ICa of the Achatina neurones. 6. Almost all of the mammalian small molecule neurotransmitters were effective on the Achatina giant neurones, suggesting that these compounds are acting on the neurones of a wide variety of animal species. However, the pharmacological features of the Achatina neurone receptors to these compounds were not fully comparable to those of the mammalian receptors. For example, we proposed that beta-hydroxy-L-glutamic acid (either threo- or erythro-) could be an inhibitory neurotransmitter for an Achatina neurone. 7. In contrast, the Achatina giant neurones appear to have no receptor for the mammalian neuroactive peptides, except for oxytocin and Arg-vasotocin. On the other hand, many neuroactive peptides were isolated from invertebrate nervous tissues, including achatin-I, a neuroexcitatory tetrapeptide having a D-phenylalanine residue.

Pharmacologic characteristics of excitatory γ-amino-butyric acid (GABA) receptors in a snail neuron

1. The pharmacologic characteristics of excitatory gamma-aminobutyric acid (GABA) receptors, termed muscimol II type GABA receptors, found in a giant neuron type, v-LCDN (ventral-left cerebral distinct neuron), of an African giant snail (Achatina fulica Férussac), were studied using the mammalian GABA receptor agonists, antagonists and synergists and GABA uptake inhibitor using the voltage clamp technique. 2. GABA and its agonists, ejected by brief pressure, produced an inward current (Iin) of the following order of potency: trans-t-aminocrotonic acid (TACA) > GABA > muscimol > isoguvacine > 5-aminopentanoic acid and cis-4-aminocrotonic acid (CACA). (+/-)-Baclofen and 3-aminopropylphosphonic acid (APPA) were ineffective. The Iin values produced by GABA, TACA, isoguvacine and CACA were stable for at least 60 min, whereas the Iin induced by muscimol was not. 3. According to the dose-response curves of GABA, TACA, isoguvacine and CACA, measured by the varied pressure duration method, the ED50 value of CACA was larger than those of the other compounds, and Emax of TACA was larger than that of GABA, whereas Emax values of isoguvacine and CACA were smaller. 4. The perfusion of beta-alanine, pentobarbital and 5-aminopentanoic acid inhibited the Iin induced by GABA, whereas (-)-bicuculline, pitrazepin, diazepam and 2-hydroxysaclofen had no effect. 5. From the effects of beta-alanine on the dose-response curves of GABA, measured by the varied pressure duration method, beta-alanine competitively inhibited the Iin caused by GABA. According to the effects of pentobarbital on the dose-response curves of GABA, this drug noncompetitively inhibited the Iin using the varied pressure duration method, and partly competitively and partly noncompetitively using the Y-tube method. The effects of 5-aminopentanoic acid on the dose-response curves of GABA indicated that this drug noncompetitively inhibited the Iin using the varied pressure duration method, and partly noncompetitively and partly uncompetitively using the Y-tube method. 6. The pharmacologic features of the Achatina muscimol II type GABA receptors were similar to those of mammalian GABAC (GABAp1) receptors, except for the effects of pentobarbital.

Modulation by APGW-amide, an Achatina endogenous inhibitory tetrapeptide, of currents induced by neuroactive compounds on Achatina neurons: peptides.

1. Modulatory effects of APGW-amide (Ala-Pro-Gly-Trp-NH2), proposed as an inhibitory neurotransmitter of Achatina neurons, perfused at 3 x 10(-6) M on the currents induced by neuroactive peptides, ejected by brief pressure, were examined by using Achatina giant neuron types, v-RCDN (ventral-right cerebral distinct neuron) and PON (periodically oscillating neuron), under voltage clamp. 2. Outward current (Iout) caused by FMRFamide (Phe-Met-Arg-Phe-NH2) on v-RCDN, which was probably K+ dependent, was inhibited with membrane conductance (g) increase by APGW-amide. From the dose (pressure duration)-response curves of FMRFamide and a Lineweaver-Burk plot of these data, the inhibition caused by APGW-amide was mainly in an uncompetitive manner. 3. Iout caused by APGW-amide on v-RCDN, which was probably K+ dependent, was inhibited with g increase by APGW-amide. The inhibition caused by APGW-amide was partly in a competitive manner and partly in a noncompetitive manner. 4. Iout caused by [Ser2]-Mytilus inhibitory peptide, [Ser2]-MIP (Gly-Ser-Pro-Met-Phe-Val-NH2) on v-RCDN, which was probably K+ dependent, was inhibited with g increase by APGW-amide. Because the modulation of this current was not so marked, a dose-response study of this compound was not carried out. Iin induced by oxytocin on PON was not affected by APGW-amide. 5. From the dose-response curves of APGW-amide, perfused consecutively, the inhibitory effects of APGW-amide on the Iout caused by APGW-amide were stronger than those on the Iout caused by FMRFamide. 6. The inhibition of the APGW-amide-induced Iout on v-RCDN by APGW-amide was partly due to the competition in the receptor sites and partly to the g increase. The inhibition by APGW-amide on the Iout induced by FMRFamide and [Ser2]-MIP would be partly due to the g increase. In addition, we consider that APGW-amide affects intracellular signal transduction systems or ionic channels, thus modulating these currents. 7. The currents modulated by APGW-amide were different from those modulated by achatin-1, another Achatina endogenous neuroexcitatory peptide. We consider that the mechanisms underlying the modulatory effects of APGW-amide are different from those of achatin-I.

Modulation by APGW-Amide, an Achatina Endogenous Inhibitory Tetrapeptide, of Currents Induced by Neuroactive Compounds on Achatina Neurons: Amines and Amino Acids

1. Modulatory effects of APGW-amide (Ala-Pro-Gly-Trp-NH2), proposed as an inhibitory neurotransmitter of Achatina neurons, perfused at 3 x 10(-6) M on the currents induced by small-molecule putative neurotransmitters were examined by using Achatina giant neuron types, v-RCDN (ventral-right cerebral distinct neuron), TAN (tonically autoactive neuron) and RAPN (right anterior pallial nerve neuron), under voltage clamp. These putative neurotransmitters were ejected locally to the neuron by brief pneumatic pressure. 2. Outward current (Iout) induced by erythro-beta-hydroxy-L-glutamic acid (erythro-L-BHGA) on v-RCDN, which was probably K+ dependent, was enhanced with membrane conductance (g) increase under APGW-amide. From dose (pressure duration)-response curves of erythro-L-BHGA measured in physiological solution (control curve) and with APGW-amide (drug curve), ED50 values of the two curves were nearly comparable, whereas Emax of the drug curve was significantly larger than that of the other. From a Lineweaver-Burk plot of these data, the cross point of the control line and the drug line was on the abscissa. 3. K(+)-dependent Iout caused by dopamine (DA) on v-RCDN was inhibited with a g increase by APGW-amide. The inhibition of this current caused by APGW-amide was mainly in a noncompetitive and partly uncompetitive manner. 4. 5-Hydroxytryptamine (5-HT) produced an inward current (Iin) with two (fast and slow) components on TAN, which was probably Na+ dependent. The fast component of the Iin was inhibited by APGW-amide. The inhibition was mainly in a noncompetitive manner. 5. The currents induced by acetylcholine, gamma-aminobutyric acid and L-glutamic acid on Achatina neuron types were not affected by APGW-amide. 6. The inhibitory effects of APGW-amide on the Iin (fast component) induced by 5-HT were nearly equipotent or a bit stronger than those on the Iout caused by DA. 7. The g increase produced by APGW-amide would be a cause for inhibiting the Iout induced by DA. In addition, we consider that APGW-amide affects intracellular signal transduction systems or ionic channels, thus modulating these currents.

Blocking effects of promethazine,triprolidine and their analogues on the excitation caused by the peptide,achatin-I

An Achatina endogenous tetrapeptide, achatin-I (Gly-d-Phe-Ala-Asp), applied by brief pressure, produced an inward current (Iin) on an Achatina giant neurone type, PON (periodically oscillating neurone). Promethazine, triprolidine and their analogues tested, applied by perfusion, showed a tendency to inhibit the Iin, suggesting that the effective structures vary to a wide extent. With respect to promethazine and its analogues, the presence of 2-bromo, 5-oxo, 3-dimethylsulfamido and 2-methoxy weakened the effects. 10-(2-methylamino-2-methylethyl) instead of 10-(2-dimethylamino-2-methylethyl) of promethazine and the azepine ring instead of phenothiazine ring potentiated the effects. From the dose (pressure duration)-response study of achatin-I, the two promethazine analogues, RP 6497 and RP 6549 (the structures are shown in Fig. 1), inhibited the Iin in partly competitive and partly noncompetitive manners. Regarding triprolidine and its analogues, the compounds in Z-configuration seemed to be more effective than those in E-configuration. The presence of 4-methyl in 1-phenyl, and 1-(4-pyridyl) instead of 1-(2-pyridyl) potentiated the effects. 3-Dimethylamino instead of 3-pyrrolidino weakened the effects. The two triprolidine analogues, Trip Der 3 and Trip Der 6 (the structures in Fig. 2), inhibited the Iin in an uncompetitive manner.

Inward Current Induced by Achatin-I Attenuated by Some H1-Receptor Antagonists and Their Analogues

Achatin-I, a neuropeptide isolated from the ganglia of Achatina fulica Ferussac, was proposed as an excitatory neurotransmitter and neuromodulator for A. fulica neurons (Kamatani et al. 1989; Kim et al. 1991; Liu and Takeuchi 1993). This peptide induced an inward current (Iin) on the giant neuron type, periodically oscillating neuron (PON). This Iin was found to be Na2+-dependent and is mediated by the cyclic AMP-PKA and calmodulin systems (Kim et al. 1991; Emaduddin et al. 1996). It was also found that some histamine H1 receptor antagonists inhibited this Iin (Santos et al. 1995). This paper, which is a part of studies on the characterization of Iin induced by achatin-I on PON, describes the suppressing effects of some H1 receptor antagonists and their analogues on this current. Their structure-activity relationship was also elucidated.

Determination of current source sites of EEG activated by mental calculation and memory recall

Wave energy has not been reported for study of the event-related potentials (ERPs). Wave energy could analyze both negative and positive potentials as a whole. Background activities, peculiar to each recording site, were considered as normalization with the energy just before the stimuli. Auditory ERPs were recorded to study the energy for eight volunteers with a contextual decision task using congruent and incongruent sentences at the terminal words. Wave energy, mean square potentials, were normalized and analyzed for post-stimulus 1024 ms. The energy for auditory contextual process showed significant difference between the incong.ruent and congruent sentences, and the left hemisphere showed significantly higher energy than that of the right hemisphere.

260 Blocking effects of promethazine triprolidine and their analogues on the excitation caused by the peptide, achatin-I

An Achatina endogenous tetrapeptide, achatin-I (Gly-D-Phe-Ala-Asp), applied by brief pressure, produced an inward current (Iin) on an Achatina giant neurone type, PON (periodically oscillating neurone). Promethazine, triprolidine and their analogues tested, applied by perfusion, showed a tendency to inhibit the Iin, suggesting that the effective structures vary to a wide extent. With respect to promethazine and its analogues, the presence of 2-bromo, 5-oxo, 3-dimethylsulfamido and 2-methoxy weakened the effects. 10-(2-methylamino-2-methylethyl) instead of 10-(2-dimethylamino-2-methylethyl) of promethazine and the azepine ring instead of phenothiazine ring potentiated the effects. From the dose (pressure duration)-response study of achatin-I, the two promethazine analogues, RP 6497 and RP 6549 (the structures are shown in Fig. 1), inhibited the Iin in partly competitive and partly noncompetitive manners. Regarding triprolidine and its analogues, the compounds in Z-configuration seemed to be more effective than those in E-configuration. The presence of 4-methyl in 1-phenyl, and 1-(4-pyridyl) instead of 1-(2-pyridyl) potentiated the effects. 3-Dimethylamino instead of 3-pyrrolidino weakened the effects. The two triprolidine analogues, Trip Der 3 and Trip Der 6 (the structures in Fig. 2), inhibited the Iin in an uncompetitive manner.