Papers by Shigenori Kawahara
Effects of the noncompetitive NMDA receptor antagonist MK-801 on classical eyeblink conditioning in mice
Neuropharmacology, Oct 1, 2001
N-methyl-d-aspartate (NMDA) receptors are involved in synaptic plasticity and play a critical rol... more N-methyl-d-aspartate (NMDA) receptors are involved in synaptic plasticity and play a critical role in learning and memory. We investigated the effects of the noncompetitive NMDA receptor antagonist (+)MK-801 on classical eyeblink conditioning of mice, using various interstimulus intervals between the conditioned stimulus (CS) and unconditioned stimulus (US). A tone was used for the CS and a periorbital shock was used
Activation of the type-1 metabotropic glutamate receptor (mGluR1) signaling pathway in the cerebe... more Activation of the type-1 metabotropic glutamate receptor (mGluR1) signaling pathway in the cerebellum involves activation of phospholipase C (PLC) and protein kinase C (PKC) for the induction of cerebellar long term depression (LTD). The PLC and PKC isoforms that are involved in LTD remain unclear, however. One previous study found no change in LTD in PKC␥-deficient mice, thus, in the present study, we examined cerebellar LTD in PLC4-deficient mice. Immunohistochemical and Western blot analyses of cerebellum from wild-type mice revealed that PLC1 was expressed weakly and uniformly, PLC2 was not detected, PLC3 was expressed predominantly in caudal cerebellum (lobes 7-10), and PLC4 was expressed uniformly throughout. In PLC4-deficient mice, expression of total PLC, the mGluR1-mediated Ca 2؉ response, and LTD induction were greatly reduced in rostral cerebellum (lobes 1-6). Furthermore, we used immunohistochemistry to localize PKC␣,-I,-II, and-␥ in mouse cerebellar Purkinje cells during LTD induction. Both PKC␣ and PKCI were found to be translocated to the plasmamembrane under these conditions. Taken together, these results suggest that mGluR1-mediated activation of PLC4 in rostral cerebellar Purkinje cells induced LTD via PKC␣ and/or PKCI. Cerebellar long term depression (LTD) 1 is produced by asso
Modulation of the feeding system by a radular mechanosensory neuron in the terrestrial slug, Incilaria fruhstorferi
Journal of Comparative Physiology A-neuroethology Sensory Neural and Behavioral Physiology, Feb 1, 1995
We investigated the modulatory role of a radular mechanoreceptor (RM) in the feeding system of In... more We investigated the modulatory role of a radular mechanoreceptor (RM) in the feeding system of Incilaria. RM spiking induced by current injection evoked several cycles of rhythmic buccal motor activity in quiescent preparations, and this effect was also observed in preparations lacking the cerebral ganglia. The evoked rhythmic activity included sequential activation of the inframedian radular tensor, the supramedian radular
Radular mechanosensory neuron in the buccal ganglia of the terrestrial slug, Incilaria fruhstorferi
Journal of Comparative Physiology A-neuroethology Sensory Neural and Behavioral Physiology, 1994
A radular mechanosensory neuron, RM, was identified in the buccal ganglia of Incilaria fruhstorfe... more A radular mechanosensory neuron, RM, was identified in the buccal ganglia of Incilaria fruhstorferi. Fine neurites ramified bilaterally in the buccal ganglia, and main neurites entered the subradular epithelium via buccal nerve 3 (n3). When the radula was distorted by bending, RM produced an afferent spike which was preceded by an axonic spike recorded at n3. The response of RM
The Journal of Neuroscience, Feb 6, 2008
The ␦2 glutamate receptor (GluR␦2) is predominantly expressed in Purkinje cells and plays crucial... more The ␦2 glutamate receptor (GluR␦2) is predominantly expressed in Purkinje cells and plays crucial roles in cerebellar functions: GluR␦2 Ϫ/Ϫ mice display ataxia and impaired motor learning. In addition, long-term depression (LTD) at parallel fiber (PF)-Purkinje cell synapses is abrogated, and synapse formation with PFs and climbing fibers (CFs) is severely disturbed in GluR␦2 Ϫ/Ϫ Purkinje cells. Recently, we demonstrated that abrogated LTD was restored in GluR␦2 Ϫ/Ϫ Purkinje cells by the virus-mediated expression of the wild-type GluR␦2 transgene (Tg wt) but not by that of mutant GluR␦2 lacking the C-terminal seven residues to which several PDZ proteins bind (Tg ⌬CT7). These results indicated that the C terminus of GluR␦2 conveys the signal(s) necessary for LTD. In contrast, other phenotypes of GluR␦2 Ϫ/Ϫ cerebellum, especially morphological abnormalities at PF and CF synapses, could not be rescued by virus-mediated transient expression. Thus, whether these phenotypes are mediated by the same signaling pathway remains unclear. To address these issues and to further delineate the function of GluR␦2 in vivo, we generated transgenic mice that expressed Tg ⌬CT7 on a GluR␦2 Ϫ/Ϫ background. Interestingly, although Tg ⌬CT7 restored abnormal PF and CF synapse formation almost completely, it could not rescue abrogated LTD in GluR␦2 Ϫ/Ϫ Purkinje cells. Furthermore, although the gross motor discoordination of GluR␦2 Ϫ/Ϫ mice was restored, the cerebellar motor learning underlying delayed eyeblink conditioning remained impaired. These results indicate that LTD induction and motor learning are regulated by signaling via the C-terminal end of GluR␦2, whereas other functions may be differentially regulated by other regions of GluR␦2.
SPAL1 interacts with the Neurabin family of proteins and is involved in the regulation of G Protein-Coupled Receptor signaling
The Molecular Biology Society of Japan, Nov 8, 2016
30aPS-89 Detection of determinism and nonlinearity in hippocampal local field potentials
Meeting abstracts of the Physical Society of Japan, Mar 5, 2014
Japanese Journal of Pharmacology, 1997
Consider homomorphisms φ: X-* Y and ψ: Y-> Z, where φ is open and N-to-one, ψ is almost periodic.... more Consider homomorphisms φ: X-* Y and ψ: Y-> Z, where φ is open and N-to-one, ψ is almost periodic. In the paper by R. J Sacker and G. R. Sell, it was shown that, under a certain condition on the phase group, the composition ψ ° φ: X-» Z is almost periodic (provided that Z is trivial and X is minimal). In this paper almost periodicity of ψ ° φ is studied under connectedness conditions on the fibers of ψ. For instance it is shown that if ψ is almost periodic with connected fibers than ψ φ is almost periodic. If ψ is locally almost periodic with locally connected fibers then φ ° ψ is locally almost periodic.
Neuroscience, 2005
Classical eyeblink conditioning has been known to depend critically on the cerebellum. Apparently... more Classical eyeblink conditioning has been known to depend critically on the cerebellum. Apparently consistent with this, glutamate receptor subunit 2 null mutant mice (GluR2-/mice), which have serious morphological and functional deficiencies in the cerebellar cortex, are severely impaired in delay paradigm. However, these mutant mice successfully learn in trace paradigm, even in '0-trace paradigm', in which the unconditioned stimulus (US) starts just after the conditioned stimulus (CS) terminates. Our previous studies revealed that the hippocampus and the muscarinic acetylcholine receptors play crucial roles in 0-trace paradigm in GluR2-/mice unlike in wild-type mice, suggesting a large contribution of the forebrain to 0-trace conditioning in this type of mutant mice. In the present study, we investigated the role of N-methyl-D-aspartate (NMDA) receptors in 0-trace eyeblink conditioning in GluR2-/mice. Mice were injected intraperitoneally with the noncompetitive NMDA receptor antagonist (+)MK-801 (0.1 mg/kg) or saline, and conditioned with 350-ms tone CS followed by 100-ms periorbital shock US. GluR2-/mice that received (+)MK-801 injection exhibited a severe impairment in acquisition of the conditioned response (CR), compared to the saline-injected GluR2-/mice. In contrast, wild-type mice were not impaired with 0-trace CR acquisition by (+)MK-801 injection. After the injection solution was changed from (+)MK-801 to saline, GluR2-/mice showed a rapid and partial recovery of CR performance. On the other hand, when the injection solution was changed from saline to (+)MK-801, GluR2-/mice showed a marked impairment in expression of the pre-acquired CR, whereas impairment of CR expression was small in wild-type mice. Injection of (+)MK-801 had no significant effects on spontaneous eyeblink frequency or startle eyeblink frequency to the tone CS in either GluR2-/mice or wild-type mice. These results suggest that NMDA receptors play critical roles both in acquisition and expression of the CR in 0-trace eyeblink conditioning in GluR2-/mice.
PLOS ONE, Jan 25, 2016
We investigated the role of muscarinic acetylcholine receptors (mAChRs) in eyeblink serial featur... more We investigated the role of muscarinic acetylcholine receptors (mAChRs) in eyeblink serial feature-positive discrimination learning in mice using the mAChR antagonist. A 2-s light cue was delivered 5 or 6 s before the presentation of a 350-ms tone paired with a 100-ms periorbital electrical shock (cued trial) but not before the tone-alone presentation (non-cued trial). Mice received 30 cued and 30 non-cued trials each day in a random order. We found that saline-injected control mice were successfully discriminating between cued and non-cued trials within a few days of conditioning. The mice responded more frequently to the tone in cued trials than in non-cued trials. Analysis of conditioned response (CR) dynamics revealed that the CR onset latency was shorter in cued trials than in non-cued trials, despite the CR peak amplitude not differing significantly between the two conditions. In contrast, scopolamine-injected mice developed an equal number of CRs with similar temporal patterns irrespective of the presence of the cue during the 7 days of conditioning, indicating in a failure to acquire conditional discrimination. In addition, the scopolamine administration to the control mice after they had successfully acquired discrimination did not impair the conditional discrimination and expression of pre-acquired CR. These results suggest that mAChRs may play a pivotal role in memory formation in the conditional brain state associated with the feature cue; however they are unlikely to be involved in the development of discrimination after conditional memory had formed in the serial feature-positive discrimination task during eyeblink conditioning.
Involvement of muscarinic acetylcholine receptors in conditional discrimination task in eyeblink conditioning in mice
F1000Research, Oct 24, 2015
The Journal of Neuroscience, 2022
Signal-induced proliferation-associated 1 (SIPA1)-like 1 (SIPA1L1; also known as SPAR1) has been ... more Signal-induced proliferation-associated 1 (SIPA1)-like 1 (SIPA1L1; also known as SPAR1) has been proposed to regulate synaptic functions that are important in maintaining normal neuronal activities, such as regulating spine growth and synaptic scaling, as a component of the PSD-95/NMDA-R-complex. However, its physiological role remains poorly understood. Here, we performed expression analyses using super-resolution microscopy (SRM) in mouse brain and demonstrated that SIPA1L1 is mainly localized to general submembranous regions in neurons, but surprisingly, not to PSD. Our screening for physiological interactors of SIPA1L1 in mouse brain identified spinophilin and neurabin-1, regulators of G-protein-coupled receptor (GPCR) signaling, but rejected PSD-95/NMDA-R-complex components. Furthermore,Sipa1l1−/−mice showed normal spine size distribution and NMDA-R-dependent synaptic plasticity. Nevertheless,Sipa1l1−/−mice showed aberrant responses to α2-adrenergic receptor (a spinophilin targ...
Journal of Experimental Biology, 1998
We investigated the morphological characteristics of physiologically characterized neurones in th... more We investigated the morphological characteristics of physiologically characterized neurones in the procerebrum (PC) of the terrestrial slug Limax marginatus. The electrophysiological characteristics of the neurones were determined using the perforated patch recording technique. By comparing the shapes and sizes of somata, we found that the somata of bursting neurones were larger and had more oblong shapes than those of nonbursting neurones, indicating that the bursting and nonbursting neurones in the PC could be discriminated on the basis of the sizes and shapes of their soma. Injection of fluorescent dyes into the bursting and nonbursting neurones revealed morphological differences in the neurites. The bursting neurones had extensive projections within the cell body layer, and the major neurites of the bursting neurones were oriented along the dorsal–ventral axis. In contrast, the nonbursting neurones had neurites extending into the neuropile layers, where terminals of both sensory...
A Cation-Channel of Tetrahymena Ciliary Membrane Reconstituted Into a Planar Lipid Bilayer
Journal of pharmacobio-dynamics, 1987
Journal of Experimental Biology, 1997
Coherent oscillatory activities in procerebral neurones have been described in Limax maximus; how... more Coherent oscillatory activities in procerebral neurones have been described in Limax maximus; however, the electrical properties of the procerebrum of other terrestrial molluscs are less well understood. We have examined oscillatory activity in the procerebrum of Incilaria bilineata and Limax marginatus. The local field potential measured in the procerebrum of I. bilineata showed repetitive peaks which had the opposite polarity from those measured in L. marginatus. Optical measurement of membrane potential using a potential-sensitive dye, di-4-ANEPPS, showed that the oscillations in I. bilineata occurred mainly in the internal mass while those in L. marginatus were located in the cell mass. An analysis of the waveform revealed that the depolarizing phase of the oscillations consists of both a slow and a rapid component in both species. The rapid component was most pronounced in the internal mass of I. bilineata but was prominent in the cell mass of L. marginatus. The superior tentac...
30aPS-89 海馬CA1の局所場電位振動における非線形時系列解析と決定論性の検出(30aPS 領域12ポスターセッション,領域12(ソフトマター物理・化学物理・生物物理))
Meeting Abstracts of the Physical Society of Japan (Nihon Butsuri Gakkai koen gaiyoshu), 2014
Rat hippocampal LFP, eyelid EMG, and stimulus timstamp (PLOS ONE Data)
3F1036 DBA/2マウスの瞬目反射条件付けにおける同側小脳核依存性(3F 神経・感覚、神経回路・脳の情報処理、行動,日本生物物理学会第49回年会)
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Papers by Shigenori Kawahara