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205 An essential role for presynaptic metabotropic glutamate receptors in the induction of mossy fiber ltd
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-203..
MULTIPLE CLIMBING FIBER INNERVATION OF CEREBELLAR METABOTROPIC GLUTAMATE RECEPTOR-l (mGluR1) MUTANT MICE.
PLJRKINJE CELLS IN MASANOBU KANO’~2,
2 1 01, Japan. “Dept. of Physiol.. Jichi Med. Sch., Minamikawachi-machi. Tochigi 329-04. Janan. 3Dept. of Anat., Hokkaido Uni. Sch. of Med.. Sapporo 606. Japan. 4Med. Inst. for Biorepulation. Kvushu Uni.. Fukuoka 812-82. Japan. 3Howard Hushes Medical Institute, Cent. for Lcarnine and Memorv. MIT, Cambridpe. MA 02139. USA. Climbing fibers (CFs) originate from the inferior olive and supply strong excitatory synapses on cerebellar Purkinje cells (PCs). Each PC is innervated by a single CF in adult mice. This is preceded, at early developmental stages, by a multiple innervation of PCs by CFs. Elimination of supernumerary CF synapses occurs during the first three postnatal weeks, and the adult-type one-to-one relation is attained on around P 20. We have previously analyzed the null mutant mice deficient in type 1 metabotropic glutamate receptor (mGluR1). The mGluR1 mutant mice show clear ataxia and impairment in motor coordination and motor learning in the behavioral tests. Electrophysiologically, the mGluR1 mutant mice showed deficiency in cerebellar long-term depression. In continuing the analysis of the mGluR1 mutant mice, we found that substantial percentage of PCs in adult mutant mice remain multiply innervated by CFs. Regression of supernumerary CFs appear to occur normally during the first and second postnatal weeks, but the elimination process in the third postnatal week is specifically impaired. Parallel fiber (PF) to PC synapses appear normal in the mGluR1 mutant mice both morphologically and electrophysiologically, excluding the possibility that the persistent multiple CF innervation is secondary to the defects in PF to PC synapses. These results demonstrate that mGluR1 is a key molecule required for elimination of supernumerary CFs during cerehellar development.
204 ($2
2 c
PRE- AND POST-SYNAPTIC MECHANISMS OF PAIRED PULSE DEPRESSION OF CLIMBING PURKINJE CELL SYNAPSES IN THE CEREBELLUM. HASHIMOTO’ KOUICHI
FIBER “I-D
Purkinje cells (PCS) in the cerebellum receive two distinct excitatory inputs from parallel fibers (PFs) and climbing fibers (CFs). The responses to CF display significant depression to the second of a stimulus pair, a phenomenon known as paired pulse depression (PPD).The duration of PPD is as long as 2 to 3 seconds, which is longer than mean inter-spike intervals of complex spikes (around 1 second). Thus, PPD is presumed to have functional significance such as modulating the amplitudes of CF-mediated excitatory postsynaptic currents (EPSCs). Mechanisms of PPD, however, are poorly understood. In the present study, we selectively manipulated either presynaptic or postsynaptic factors of synaptic transmission, and examined the effects of these experimental manipulations on PPD of CF-EPSCs. At inter-stimulus intervals (ISIS) longer than SOms, the amount of PPD was significantly affected by manipulations that selectively change transmitter release from presynaptic terminals. These include lowering extracellular Ca2+concentration and bath application of baclofen or adenosine. In contrast, manipulations that selectively change postsynaptic responsiveness had no effect on the amount of PPD. These included partial blockade of postsynaptic non-NMDA receptors by CNQX, and changing the holding potentials. We also found that removal of glutamate receptor desensitization by d&oxide significantly reduced the amount of PPD only at ISIS shorter than 50ms. D&oxide had no significant effects on the amount of PPD at ISIS longer than 50ms. These results suggest that PPD is mainly due to the decreased transmitter release from presynaptic terminals at ISIS longer than 50ms. Desensitization of postsynaptic glutamate receptors also significantly contributes to PPD only at ISIS shorter than 50ms.
205 Sp Neuroh siol BC
AN ESSENTIAL ROLE FOR PRESYNAPTIC THE INDUCTION OF MOSSY FIBER LTD.
MEI’ABOTROPIC GLUTAMATE RECEPTORS IN KATSUNORI KOBAYASHI’. MINETO YOKOI’. nt of
Long-term depression (LTD) of excitatory synaptic transmission between mossy fibers and CA3 pyramidal cells can be induced by low-frequency stimulation (LFS) of mossy fibers in mouse hippocampal slices. The induction of mossy In mice lacking mGluR2, mossy fiber LTD was blocked by an antagonist of metabotropic glutamate receptors (mGluRs). fiber LTD was severely impaired. At the mossy fiber-CA3 synapse, mGluR2 is expressed only at the presynaptic site, indicating that presynaptic mGluR2 plays a crucial mle in the LTD induction. Since application of mGluR agonists caused only reversible synaptic depression, additional factor(s) should be required. The LTD induction was not prevented by blockade of postsynaptic depolarization. Thus, activation of pmsynaptic mGluRs in combination with presynaptic activity during LFS may induce mossy fiber LTD.
-203..
MULTIPLE CLIMBING FIBER INNERVATION OF CEREBELLAR METABOTROPIC GLUTAMATE RECEPTOR-l (mGluR1) MUTANT MICE.
PLJRKINJE CELLS IN MASANOBU KANO’~2,
2 1 01, Japan. “Dept. of Physiol.. Jichi Med. Sch., Minamikawachi-machi. Tochigi 329-04. Janan. 3Dept. of Anat., Hokkaido Uni. Sch. of Med.. Sapporo 606. Japan. 4Med. Inst. for Biorepulation. Kvushu Uni.. Fukuoka 812-82. Japan. 3Howard Hushes Medical Institute, Cent. for Lcarnine and Memorv. MIT, Cambridpe. MA 02139. USA. Climbing fibers (CFs) originate from the inferior olive and supply strong excitatory synapses on cerebellar Purkinje cells (PCs). Each PC is innervated by a single CF in adult mice. This is preceded, at early developmental stages, by a multiple innervation of PCs by CFs. Elimination of supernumerary CF synapses occurs during the first three postnatal weeks, and the adult-type one-to-one relation is attained on around P 20. We have previously analyzed the null mutant mice deficient in type 1 metabotropic glutamate receptor (mGluR1). The mGluR1 mutant mice show clear ataxia and impairment in motor coordination and motor learning in the behavioral tests. Electrophysiologically, the mGluR1 mutant mice showed deficiency in cerebellar long-term depression. In continuing the analysis of the mGluR1 mutant mice, we found that substantial percentage of PCs in adult mutant mice remain multiply innervated by CFs. Regression of supernumerary CFs appear to occur normally during the first and second postnatal weeks, but the elimination process in the third postnatal week is specifically impaired. Parallel fiber (PF) to PC synapses appear normal in the mGluR1 mutant mice both morphologically and electrophysiologically, excluding the possibility that the persistent multiple CF innervation is secondary to the defects in PF to PC synapses. These results demonstrate that mGluR1 is a key molecule required for elimination of supernumerary CFs during cerehellar development.
204 ($2
2 c
PRE- AND POST-SYNAPTIC MECHANISMS OF PAIRED PULSE DEPRESSION OF CLIMBING PURKINJE CELL SYNAPSES IN THE CEREBELLUM. HASHIMOTO’ KOUICHI
FIBER “I-D
Purkinje cells (PCS) in the cerebellum receive two distinct excitatory inputs from parallel fibers (PFs) and climbing fibers (CFs). The responses to CF display significant depression to the second of a stimulus pair, a phenomenon known as paired pulse depression (PPD).The duration of PPD is as long as 2 to 3 seconds, which is longer than mean inter-spike intervals of complex spikes (around 1 second). Thus, PPD is presumed to have functional significance such as modulating the amplitudes of CF-mediated excitatory postsynaptic currents (EPSCs). Mechanisms of PPD, however, are poorly understood. In the present study, we selectively manipulated either presynaptic or postsynaptic factors of synaptic transmission, and examined the effects of these experimental manipulations on PPD of CF-EPSCs. At inter-stimulus intervals (ISIS) longer than SOms, the amount of PPD was significantly affected by manipulations that selectively change transmitter release from presynaptic terminals. These include lowering extracellular Ca2+concentration and bath application of baclofen or adenosine. In contrast, manipulations that selectively change postsynaptic responsiveness had no effect on the amount of PPD. These included partial blockade of postsynaptic non-NMDA receptors by CNQX, and changing the holding potentials. We also found that removal of glutamate receptor desensitization by d&oxide significantly reduced the amount of PPD only at ISIS shorter than 50ms. D&oxide had no significant effects on the amount of PPD at ISIS longer than 50ms. These results suggest that PPD is mainly due to the decreased transmitter release from presynaptic terminals at ISIS longer than 50ms. Desensitization of postsynaptic glutamate receptors also significantly contributes to PPD only at ISIS shorter than 50ms.
205 Sp Neuroh siol BC
AN ESSENTIAL ROLE FOR PRESYNAPTIC THE INDUCTION OF MOSSY FIBER LTD.
MEI’ABOTROPIC GLUTAMATE RECEPTORS IN KATSUNORI KOBAYASHI’. MINETO YOKOI’. nt of
Long-term depression (LTD) of excitatory synaptic transmission between mossy fibers and CA3 pyramidal cells can be induced by low-frequency stimulation (LFS) of mossy fibers in mouse hippocampal slices. The induction of mossy In mice lacking mGluR2, mossy fiber LTD was blocked by an antagonist of metabotropic glutamate receptors (mGluRs). fiber LTD was severely impaired. At the mossy fiber-CA3 synapse, mGluR2 is expressed only at the presynaptic site, indicating that presynaptic mGluR2 plays a crucial mle in the LTD induction. Since application of mGluR agonists caused only reversible synaptic depression, additional factor(s) should be required. The LTD induction was not prevented by blockade of postsynaptic depolarization. Thus, activation of pmsynaptic mGluRs in combination with presynaptic activity during LFS may induce mossy fiber LTD.