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Yutaka Kirino

Publications and source records attributed to Yutaka Kirino.

At least 19 recordsLinked to original sources
PubMed2006

The procerebrum is necessary for odor-aversion learning in the terrestrial slug Limax valentianus.

The terrestrial slug Limax has a highly developed ability to associate the odor of some foods (e.g., carrot juice) with aversive stimuli such as the bitter taste of quinidine solution. The procerebrum (PC) is a part of the slug's brain thought to be involved in odor-aversion learning, but direct evidence is still lacking. Here we present evidence showing that the PC is essential for odor-aversion learning. Unlike sham-operated slugs, PC ablation 7 d prior to conditioning showed that most slugs did not avoid carrot juice in the memory retention test conducted 24 h after the conditioning. Slugs with the PC ablated 3 h, 1 d, 3 d, or 7 d after conditioning and examined by the memory retention test at 3 d after the PC ablation were also less likely to avoid carrot juice than sham-operated slugs. The PC ablation did not damage the ability of the slugs to sense attractive odor (everyday food) or innately aversive odor (onion or garlic). These results demonstrate that the PC is a necessary component in the retention and/or retrieval of odor-aversion memory.

Animals↗
PubMed2006

Air movement evokes electro-olfactogram oscillations in the olfactory epithelium and modulates olfactory processing in a slug.

In many animals, neurons in the olfactory system have been shown to respond not only to odorants but also to air movements. However, the manner in which the mechanical dynamics of odor stimulation affect olfactory processing remains poorly understood. Using a series of flow rates and odor concentrations from clean air to high-concentration vapors, we systematically analyzed the effects of air movement and odor concentration on olfactory processing. We extracellularly recorded local field potentials and spike units from the olfactory epithelium (OE) and tentacular nerve (TN), which connects the first and second relay centers of olfactory information, in the terrestrial slug Limax marginatus. We found that clean air puffs at a flow rate of 0.18 ml/s (gentle wind), but not high-concentration odor puffs at lower flow rates, induced electro-olfactogram (EOG) oscillations in the OE with a constant frequency (2.5 Hz), regardless of the odor. Surgically isolated OE preparations also showed these EOG oscillations, indicating that the oscillations arose from the OE independently of the downstream circuits. The EOG oscillations entrained the slower spontaneous TN oscillations (1-2 Hz) to the fixed rhythm (2.5 Hz). Spontaneous and odor-evoked units were phase-locked to the TN oscillation peaks. This TN oscillation entrainment by the EOG oscillations caused stronger phase-locking, specifically TN oscillation peaks and EOG oscillation troughs. Taken together, these results suggest that when odors are carried by a gentle wind, the air movement induces EOG oscillations and modulates rhythmic spike patterning of olfactory outputs to the second olfactory relay center in Limax.

Action Potentials↗
PubMed2006

Depletion of serotonin selectively impairs short-term memory without affecting long-term memory in odor learning in the terrestrial slug Limax valentianus.

The terrestrial slug Limax is able to acquire short-term and long-term memories during aversive odor-taste associative learning. We investigated the effect of the selective serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) on memory. Behavioral studies indicated that 5,7-DHT impaired short-term memory but not long-term memory. HPLC (high-performance liquid chromatography) analysis revealed that 5,7-DHT significantly reduced serotonin content in the central nervous system. The present study suggests that acquisition, retention, and/or retrieval of short-term memory involves serotonin, and neither acquisition nor retrieval of long-term memory requires serotonin at a level as high as that required for short-term memory.

5,7-Dihydroxytryptamine↗
PubMed2006

Systems consolidation requires postlearning activation of NMDA receptors in the medial prefrontal cortex in trace eyeblink conditioning.

The importance of the hippocampus in declarative memory is limited to recently acquired memory, and remotely acquired memory is believed to be stored somewhere in the neocortex. However, it remains unknown how the memory network is reorganized from a hippocampus-dependent form into a neocortex-dependent one. We reported previously that the medial prefrontal cortex (mPFC) is important for this neocortex-dependent remote memory in rat trace eyeblink conditioning. Here, we investigate the involvement of NMDA receptors in the mPFC in this reorganization and determine the time window of their contribution using chronic infusion of an antagonist into the mPFC, specifically during the postlearning consolidation period. The rats with blockade of the mPFC NMDA receptors during the first 1 or 2 weeks after learning showed a marked impairment in memory retention measured 6 weeks after learning, but relearned normally with subsequent conditioning. In contrast, the same treatment had no effect if it was performed during the third to fourth weeks or during the first day just after learning. The specificity of NMDA receptor blockade was confirmed by the reduced long-term potentiation in the hippocampal-prefrontal pathway in these rats. These results suggest that successful establishment of remotely acquired memory requires activation of NMDA receptors in the mPFC during at least the initial week of the postlearning period. Such NMDA receptor-dependent processes may mediate the maturation of neocortical networks that underlies permanent memory storage and serve as a way to reorganize memory circuitry to the neocortex-dependent form.

Animals↗
PubMed2006

In vitro odor-aversion conditioning in a terrestrial mollusk.

We developed an in vitro odor-aversion conditioning system in the terrestrial mollusk, Limax, and found a behavioral correlate of network oscillation in the olfactory CNS. We first examined the odor-induced behavior of Limax, after odor-aversion conditioning in vivo. Shortening of mantle muscles was specifically observed in response to aversively conditioned odors. We previously identified that parietal nerves, which project to the mantle muscle in Limax, regulate shortening of the mantle muscle. We therefore isolated whole brains containing noses (sensory organs) and parietal nerves (motor output), and applied an odor-aversion conditioning paradigm to these in vitro preparations. Before the in vitro conditioning, application of attractive odors to the noses did not elicit any discharge in the parietal nerves. However, after odor-aversion conditioning, discharges in the parietal nerves were observed in response to the natively attractive but aversively conditioned odors. We also found that network oscillation frequency in the procerebrum (PC), the olfactory CNS of Limax, increased specifically in response to the aversively conditioned odors that elicited avoidance behavior. In naive (nonconditioned) preparations, increases in the PC oscillation frequency were observed specifically in response to innately aversive odors. These results indicate that the isolated brains have an ability of odor learning. They also suggest that changes in PC network oscillation are associated with aversively conditioned and innately aversive odors, both of which elicit avoidance behavior. This in vitro conditioning system would be an effective approach for exploring the neural mechanism to determine the aversion to odors.

Action Potentials↗
PubMed2006

Novel kruppel-like factor is induced by neuronal activity and by sensory input in the central nervous system of the terrestrial slug Limax valentianus.

In the Limax central nervous system, the procerebrum is thought to be the locus of odor information processing and odor memory retention, but little is known about the input pathway of the noxious stimuli used in this learning protocol. To gain insight into the sensory information processing of the noxious stimuli involved in memory formation, we screened genes induced by artificial neuronal activity, and identified one kruppel-like factor (KLF) family transcription factor gene (Limax KLF; limKLF), which is up-regulated 30 min after depolarization. The limKLF protein fused to GFP was localized to the nucleus in COS-7 cells. We also cloned an immediate early gene, CCAAT enhancer binding protein (C/EBP), of Limax by reverse transcription-polymerase chain reaction (RT-PCR). Both genes were up-regulated by dissection of the central nervous system (CNS) out of the slug in a protein synthesis-independent manner, and also by various noxious stimuli to the slug's body. These genes may be useful as neuronal activity markers in Limax to visualize activated sensory nervous systems.

Amino Acid Sequence↗
PubMed2006

Hippocampal CA3 NMDA receptors are crucial for adaptive timing of trace eyeblink conditioned response.

Classical conditioning of the eyeblink reflex is a simple form of associative learning for motor responses. To examine the involvement of hippocampal CA3 NMDA receptors (NRs) in nonspatial associative memory, mice lacking an NR1 subunit selectively in adult CA3 pyramidal cells [CA3-NR1 knock-out (KO) mice] were subjected to eyeblink conditioning paradigms. Mice received paired presentations of an auditory conditioned stimulus (CS) and a periorbital shock unconditioned stimulus (US). With repeated presentation of the CS followed by the US, wild-type mice learned to blink in anticipation of the US before its onset. We first confirmed that wild-type mice require an intact hippocampus in the trace version of eyeblink conditioning in which the CS and US do not overlap, creating a stimulus-free time gap of 500 ms. Under the same condition, CA3-NR1 KO mice successfully acquired conditioned responses (CRs) during the 10 d acquisition sessions, whereas the extinction of CRs was impaired on the first day of extinction sessions. Importantly, CA3-NR1 KO mice were impaired in the formation of an adaptively timed CR during the first five trials in the daily acquisition sessions. The aberrantly timed CR was also observed in the extinction sessions in accordance with the impaired extinction of CRs. These results indicate that CA3-NR1 KO mice are unable to rapidly retrieve adaptive CR timing, suggesting that CA3 NRs play a crucial role in the memory of adaptive CR timing in trace conditioning.

Adaptation, Physiological↗
PubMed2006

Mapping of odor-related neuronal activity using a fluorescent derivative of glucose.

Activity labeling was applied to the olfactory systems of the terrestrial slug Limax valentianus using 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG), a fluorescent derivative of glucose. 2-NBDG was incorporated into cultured Limax olfactory interneurons, and this was partially blocked by the presence of a high concentration of glucose in the medium, indicating that a part of the uptake of 2-NBDG is mediated by glucose transporters. Next, in order to map odor-related neuronal activity in the primary olfactory center, tentacular ganglion, we injected 2-NBDG into the body cavities of slugs and exposed them to odors or clean air (control). In the odor-stimulated animals, the cell mass region was strongly stained. The digit-like extensions and the neuropil region were also stained in some animals. The control animals showed no staining. The neurons in the cell mass are thought to be involved in generating oscillating activities in the tentacular ganglion, and their activation may imply modulation of oscillatory activity during odor processing. Our results show that 2-NBDG is useful for mapping neuronal activity in vivo.

4-Chloro-7-nitrobenzofurazan↗
PubMed2005

Purkinje cell activity during classical eyeblink conditioning in decerebrate guinea pigs.

Purkinje cells are the sole output from the cerebellar cortex and play a critical role during classical eyeblink conditioning. The present study revealed for the first time a learning-related change in individual Purkinje cell activity during successive eyeblink conditioning in decerebrate guinea pigs which permitted continuous single unit recording from the simplex lobe of the cerebellar cortex. The pair-conditioned group received paired presentation of the conditioned stimulus (CS) and unconditioned stimulus (US) until the frequency of the conditioned response (CR) exceeded 80%. The control group received a comparable number of the CS and US in a pseudorandom fashion. Responses of Purkinje cells to the CS were classified into four types: excitatory, inhibitory, a combination of the two, or no response. Approximately half of the recorded cells from both groups changed their response type at various conditioning stages. The firing frequency of a Purkinje cell to the CS showed a tendency to decrease in the pair-conditioned group, while it had a tendency to increase in the pseudoconditioned group. This learning-related difference in change of response type was attributable to a difference in the change between the no response and the inhibitory response types. Correlation analysis of the temporal pattern between the neural activity and the CR revealed that most of the cells that developed an inhibitory response by paired conditioning acquired the CR-related temporal pattern. These results suggest that the learning-related Purkinje cells gain an inhibitory response with a temporal pattern correlated with the CR topography.

Acoustic Stimulation↗
PubMed2005

Characterization of hippocampal theta rhythm in wild-type mice and glutamate receptor subunit delta2 mutant mice during eyeblink conditioning with a short trace interval.

We have shown that glutamate receptor subunit delta2 (GluRdelta2) null mutant mice, which have serious morphological and functional deficiencies in the cerebellar cortex, are severely impaired in delay eyeblink conditioning but not in trace eyeblink conditioning, even with a 0-trace interval. Such 0-trace conditioning does not depend critically on the hippocampus in wild-type mice, but it does in GluRdelta2 mutant mice. Here we examined the hippocampal electroencephalogram (EEG) during 0-trace conditioning in GluRdelta2 mutant and wild-type mice. During the apparatus habituation sessions, the total hippocampal theta activity (4-12 Hz) of GluRdelta2 mutant mice was less than that of wild-type mice. Activity in the higher frequency band (8-12 Hz, type 1) in GluRdelta2 mutant mice was significantly less than it was in wild-type mice, but activity in the lower frequency band (4-8 Hz, type 2) was not. As learning proceeded during the acquisition sessions, the total theta activity decreased in many of the wild-type mice, while this phenomenon was less prominent in GluRdelta2 mutant mice. Further analysis showed that the type 1 activity in wild-type mice increased in the early sessions and then decreased, while that in GluRdelta2 mutant mice did not change. Type 2 activity tended to decrease in both types of mice as the conditioning proceeded. These results indicate that the distribution of hippocampal EEG frequency and its properties during conditioning are different between wild-type and GluRdelta2 mutant mice, suggesting that the cerebellar cortical dysfunction may cause an alteration in the electrophysiological characteristics of the hippocampus.

Animals↗
PubMed2005

State-dependent sensory gating in olfactory cortex.

Sensory systems show behavioral state-dependent gating of information flow that largely depends on the thalamus. Here we examined whether the state-dependent gating occurs in the central olfactory pathway that lacks a thalamic relay. In urethane-anesthetized rats, neocortical EEG showed a periodical alternation between two states: a slow-wave state (SWS) characterized by large and slow waves and a fast-wave state (FWS) characterized by faster waves. Single-unit recordings from olfactory cortex neurons showed robust spike responses to adequate odorants during FWS, whereas they showed only weak responses during SWS. The state-dependent change in odorant-evoked responses was observed in a majority of olfactory cortex neurons, but in only a small percentage of olfactory bulb neurons. These findings demonstrate a powerful state-dependent gating of odor information in the olfactory cortex that works in synchrony with the gating of other sensory systems. They suggest a state-dependent switchover of signal processing modes in the olfactory cortex.

Animals↗
PubMed2005

Role of hippocampal NMDA receptors in trace eyeblink conditioning.

We examined the effects of acute injections of competitive N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovaleric acid (APV) into the dorsal hippocampus on contextual fear conditioning and classical eyeblink conditioning in C57BL/6 mice. When injected 10 to 40 min before training, APV severely impaired contextual fear conditioning. Thus, APV injection under these conditions was sufficient to suppress hippocampal NMDA receptors. To investigate the role of hippocampal NMDA receptors on eyeblink conditioning, we carried out daily training of mice during 10-40 min after injection of APV. In the delay eyeblink conditioning, in which the unconditioned stimulus (US) is delayed and terminates simultaneously with the conditioned stimulus (CS), APV-injected mice acquired the conditioned responses (CRs) as well as artificial cerebrospinal fluid (aCSF)-injected control mice did. However, in the trace eyeblink conditioning, in which the CS and US were separated by a stimulus-free trace interval of 500 ms, APV-injected mice showed severe impairment in acquisition of the CR. There was no significant difference in pseudo-conditioning between APV- and aCSF-injected mice. These results provide evidence that the NMDA receptor in the dorsal hippocampus is critically involved in acquisition of the CR in long trace eyeblink conditioning.

2-Amino-5-phosphonovalerate↗
PubMed2005

Interaction of N-terminal acetyltransferase with the cytoplasmic domain of beta-amyloid precursor protein and its effect on A beta secretion.

The processing of beta-amyloid precursor protein (APP) generates the amyloid beta-protein (A beta) and contributes to the development of Alzheimer's disease (AD). Elucidating the regulation of APP processing will, therefore, contribute to the understanding of AD. Many APP-binding proteins, such as FE65, X11s, and JNK-interacting proteins (JIPs), bind the motif 681-GYENPTY-687 within the cytoplasmic domain of APP. Here we found that the human homologue of yeast amino-terminal acetyltransferase ARD1 (hARD1) interacts with a novel motif, 658-HGVVEVD-664, in the cytoplasmic domain of APP695. hARD1 expressed its acetyltransferase activity in association with a human subunit homologous to another yeast amino-acetyltransferase, hNAT1. Co-expression of hARD1 and hNAT1 in cells suppressed A beta40 secretion and the suppression correlated with their enzyme activity. These observations suggest that the association of APP with hARD1 and hNAT1 and/or their N-acetyltransferase activity contributes to the regulation of A beta generation.

Acetyltransferases↗
PubMed2004

Impairment of olfactory discrimination by blockade of nitric oxide activity in the terrestrial slug Limax valentianus.

The terrestrial slug Limax readily associates an innately preferred food odor with the aversive taste of quinidine. We investigated slugs' olfactory discrimination capability among structurally similar alcohols and the effects of inhibition of nitric oxide (NO) synthesis to the olfactory discrimination behavior, using an olfactory discriminatory learning task. Limax could discriminate among the odor of 1-octanol (OT), 3-methylcyclohexanol (MC) and 1-hexanol (HX). OT was perceptually more similar to HX than was MC for them. When NO synthesis was inhibited by injecting N-nitro-L-arginine methyl ester (l-NAME) shortly before the discrimination test, slugs could not discriminate between OT and HX whereas the retrieval of olfactory memory and the discrimination between OT and MC remained intact. These results indicate that the NO cascade plays a crucial role for fine olfactory discrimination in Limax.

Animals↗
PubMed2004

The N-methyl-D-aspartate (NMDA)-type glutamate receptor GluRepsilon2 is important for delay and trace eyeblink conditioning in mice.

It has been proposed that the N-methyl-d-aspartate (NMDA)-type glutamate receptor (GluR) plays an important role in synaptic plasticity, learning, and memory. The four GluRepsilon (NR2) subunits, which constitute NMDA receptors with a GluRzeta (NR1) subunit, differ both in their expression patterns in the brain and in their functional properties. In order to specify the distinct participation of each of these subunits, we focused on the GluRepsilon2 subunits, which are expressed mainly in the forebrain. We investigated delay and trace eyeblink conditioning in GluRepsilon2 heterozygous mutant mice whose content of GluRepsilon2 protein was decreased to about half of that in wild-type mice. GluRepsilon2 mutant mice exhibited severe impairment of the attained level of conditioned response (CR) in the delay paradigm, for which the cerebellum is essential and modulation by the forebrain has been suggested. Moreover, GluRepsilon2 mutant mice showed no trend toward CR acquisition in the trace paradigm with a trace interval of 500 ms, in which the forebrain is critically involved in successful learning. On the other hand, the reduction of GluRepsilon2 proteins did not disturb any basic sensory and motor functions which might have explained the observed impairment. These results are different from those obtained with GluRepsilon1 null mutant mice, which attain a normal level of the CR but at a slower rate in the delay paradigm, and showed a severe impairment in the trace paradigm. Therefore, the NMDA receptor GluRepsilon2 plays a more critical role than the GluRepsilon1 subunit in classical eyeblink conditioning.

Analysis of Variance↗
PubMed2004

Slow Ca2+ dynamics in pharyngeal muscles in Caenorhabditis elegans during fast pumping.

The pharyngeal muscles of Caenorhabditis elegans are composed of the corpus, isthmus and terminal bulb from anterior to posterior. These components are excited in a coordinated fashion to facilitate proper feeding through pumping and peristalsis. We analysed the spatiotemporal pattern of intracellular calcium dynamics in the pharyngeal muscles during feeding. We used a new ratiometric fluorescent calcium indicator and a new optical system that allows simultaneous illumination and detection at any two wavelengths. Pumping was observed with fast, repetitive and synchronous spikes in calcium concentrations in the corpus and terminal bulb, indicative of electrical coupling throughout the muscles. The posterior isthmus, however, responded to only one out of several pumping spikes to produce broad calcium transients, leading to peristalsis, the slow and gradual motion needed for efficient swallows. The excitation-calcium coupling may be uniquely modulated in this region at the level of calcium channels on the plasma membrane.

Animals↗
PubMed2004

Optical recording of oscillatory neural activities in the molluscan brain.

The procerebrum (PC) of the terrestrial slug shows a coherent oscillatory activity. Information is encoded in the PC by neurons with synchronized oscillatory activity, and the oscillatory activity will propagate to other brain regions as the PC transmits information. Using the optical recording of membrane potentials and the correlation analysis, we showed that the metacerebrum/mesocerebrum (MC) region also shows an oscillatory activity coherent with that of the PC. The MC oscillation was either inphase or antiphase with the PC oscillation, and its amplitude was larger when it was antiphase than it was inphase. These results indicate that the MC is capable of producing an oscillatory activity, possibly driven by synaptic input from the PC.

Action Potentials↗