シンポジウム

シンポジウム Significance of the temporal structure within network activities in the striatum and the limbic system.

2S6-1 Slow inhibitory oscillation in the basolateral amygdala and its alteration by stress load Hashizume Miki¹，Shinozaki Rina¹，Mukai Hideo²，Yanagawa Yuchio³，Murakoshi Takayuki¹ ¹Department of Biochemistry, Faculty of Medicine, Saitama Medical University，²Department of Computer Science, School of Science and Technology, Meiji University，³Department of Genetic and Behavioral Neuroscience, Gunma University Graduate School of Medicine Basolateral amygdaloid complex（BLA）is deeply involved in emotional processing and is sensitive to chronic stress. Its abnormality is related to several psychiatric disorders. In the BLA, sensory information from the cortex and the thalamus are evaluated in terms of emotional valence and these signals are transmitted to central nucleus of amygdala. Previously, we showed that projection neurons in BLA receive rhythmic inhibitory inputs which are evoked by synchronous firings of interneurons. Such neurons were mostly distributed in ventral part of BLA. In addition, this inhibitory oscillation requires the glutamatergic transmission within BLA, suggesting that local network activities are essential for the oscillation. In the present study, we examined the effect of sleep deprivation（SD）on the BLA because the frequency of slow inhibitory oscillation（0.1-3 Hz）is similar to that of delta wave（1-4 Hz）observed in LA of animals during slow wave sleep. Thereby we examined the effects of SD on properties of projection neurons or inhibitory interneurons in rat BLA to reveal the physiological significance of the inhibitory network oscillation. We applied acute SD（morning, 3 hours）on juvenile Wistar rats（P14-24）. Rats were held in the cage where 1.5-2 cm height of water was filled. Thereafter, coronal slices were immediately prepared for whole-cell recording. We found that power of the low-frequency（0.1-3 Hz）oscillation（rhythmic inhibitory inputs）was decreased in SD rats. The decline was caused by a reduction of synaptic current amplitude. In addition, spike firing of inhibitory interneurons was attenuated. These results suggest that stress by sleep disturbance modulates the magnitude of network oscillation by reducing the interneuronal activity in BLA.		2S6-2 Metabotropic glutamate receptor sensitive slow calcium oscillations in striatum. Osanai Makoto Tohoku Univ. Grad. Sch. Med. The striatum receives inputs from the cortex and is thought to play a crucial role in controlling somatic motor movements, behavioral patterns, cognition, learning, and memory. Ca²⁺ is a universal intracellular messenger, and plays enormous versatile rolls in cells. However, the properties of the Ca²⁺ signaling in the striatum remain less understood.There are many types of metabotropic receptors that may contribute to intracellular Ca²⁺ signaling in the striatum. Group I mGluRs, which are known to modulate the intracellular Ca²⁺ signaling, are densely expressed in the striatum.We have found the long-lasting spontaneous calcium transients（slow Ca²⁺ oscillation）, which lasted up to about 300 s, in the striatal neurons and astrocytes. Neither the inhibition of action potentials nor ionotropic glutamate receptors blocked the slow Ca²⁺ oscillation. Depletion of the intracellular Ca²⁺ store and the blocking IP3 receptors diminished the slow Ca²⁺ oscillations. The application of an antagonist against mGluR5 also blocked the slow Ca²⁺ oscillations in both putative-neurons and astrocytes. Thus, the mGluR5-IP3 signal cascade is the primary contributor to the slow Ca²⁺ oscillation in both putative-neurons and astrocytes.The slow Ca²⁺ oscillations have poor regularity but feature multicellular synchrony. In the condition of blockade of action potentials, the regularity of the Ca²⁺ oscillations was increased, however the cellular correlation of the Ca²⁺ oscillations was reduced. These phenomena were observed only in the corticostriatal slice but not in the striatal slice. Thus, the cortical activities might contribute to the slow Ca²⁺ oscillations.Intracellular Ca²⁺ can modulate various proteins, thus, the slow Ca²⁺ oscillations we found may regulate the cellular functions leading to change the state of cellular networks in the striatum. Though in a simulation study, we found out that the slow Ca²⁺ oscillation could alter the firing rate of the medium spiny neuron via modulation of Ca²⁺-activated potassium channels.mGluR5 has also been suggested as a therapeutic target for Parkinson’s disease and may interact with dopamine signaling via Ca²⁺. Dopamine signaling is essential for neuronal functioning in the striatum. Thus, the slow Ca²⁺ oscillation is expected to play a role in information processing in the striatum.

2S6-3 Optogenetically-induced seizure and longitudinal hippcampal network dynamics Osawa Shin-ichiro^1,2，Iwasaki Masaki¹，Hosaka Ryosuke³，Matsuzaka Yoshiya⁴，Tomita Hiroshi⁵，Ishizuka Toru⁶，Yawo Hiromu⁶，Nakasato Nobukazu⁷，Mushiake Hajime⁴，Tominaga Teiji¹ ¹Dept. of Neurosurgery, Tohoku Univ. Graduate School of Medicine，²Dept. of Neurosurgery, Hachinohe City Hospital，³Dept. of Applied Mathematics, Fukuoka Univ.，⁴Dept. of Physiology, Tohoku Univ. Graduate School of Medicine，⁵Laboratory of Visual Neuroscience, Dept. of Chemistry and Bioengineering, Iwate Univ.，⁶Dept. of Developmental Biology and Neuroscience, Tohoku Univ. Graduate School of Life Sciences，⁷Dept. of Epileptology, Tohoku Univ. Graduate School of Medicine，⁸Japan Science and Technology Agency（JST）, Core Research of Evolutional Science ＆ Technology（CREST） Background Epileptic seizure is a paroxysmal and self-limited phenomenon characterized by abnormal hypersynchrony of a large population of neurons. But our current understanding of seizure dynamics is still limited. Traditional animal model of epileptic seizure by electrical stimulation generates large artifacts which interfere with recordings of neuronal activities in animal model. Methods/Results Here we propose a novel in vivo model of epileptic seizures using optogenetics. Repetitive pulse photo-stimulation induced seizures in the hippocampus of Thy1.2-ChR2-Venus transgenic rat. Simultaneous multisite recordings and immunohistochemical study by c-Fos staining revealed the seizure involved the entire hippocampus along the longitudinal（septo-temporal, ST）axis. Granger causality analysis of local field potentials recorded with multi-contact array electrode inserted along the ST axis of hippocampus showed a bidirectional but asymmetric increase in signal flow along the ST direction. State space presentation of the causality and coherence revealed three discrete states of the seizure phenomenon：1）resting state；2）afterdischarge initiation with moderate coherence and dominant septal-to-temporal causality；and 3）afterdischarge termination with increased coherence and dominant temporal-to-septal causality. Conclusions/Significance This novel hippocampal seizure model was advantageous in its reproducibility and artifact-free electrophysiological observations. Our results provide additional evidence for the potential role of hippocampal ST interactions alternating in temporal cource in seizure phenomenon.		2S6-4 Electrophysiological temporal property of the striatum Ohta Hiroyuki Department of Physiology, National Defense Medical College The striatum is related to motor function, as well as other 1st person cognitive processes such as action selection, action execution and re-evaluation of the executed action. These striatal functions are processed in time, within several seconds, suggesting the necessity of investigating striatal time-domain properties. In order to understand the temporal structure of the striatal activities, we assessed a temporal summation of synaptic potentials of adult rodent medium spiny neurons and a firing probability modulation after the depolarization. We found that the striatal neuron in acute slice was able to respond to low frequency synaptic stimulations and sum up the potentials；the maximum inter-stimulus interval（ISI）to observe the potential summation was 100-ms, while the cortex layer 5 pyramidal neurons have shorter temporal summation ability：the maximum ISI is 25-ms（Reyes and Sakmann 1999）. We also investigated the firing probability modulation after optogenetic stimulation. The striatal neurons showed a prolonged firing response of gradually increasing duration when exposed to repetitive optogenetic photostimulation. The prolonged firing response also recurred after a long intermission of up to 20 sec. These results indicate that the striatum has a characteristic time-domain property of the synaptic input integration, suggesting that the prolonged property could be a new pharmacological target.