Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice

Aiba, Atsu; Kano, Masanobu; Chen, Chong; Stanton, Mark E.; Fox, Gregory D.; Herrup, Karl; Zwingman, Theresa; Tonegawa, Susumu

doi:10.1016/0092-8674(94)90205-4

Cited by 749 publications

(558 citation statements)

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“…The stimulation protocol we applied produces reliable, nearly saturating depression. The same and similar protocols have revealed impaired LTD in other mutant mouse models tested in our and other laboratories (Aiba et al, 1994;Conquet et al, 1994;Kashiwabuchi et al, 1995;De Zeeuw et al, 1998b).…”

Section: Ltd At the Parallel Fiber 3 Purkinje Cell Synapsesupporting

confidence: 64%

“…A key event in LTD induction is the activation of postsynaptic metabotropic glutamate receptors (mGluRs) (Rose and Konnerth, 2001). Mice null mutant for mGluR1, a subtype of mGluRs that is expressed in Purkinje cells (Martin et al, 1992;Gorcs et al, 1993;Ryo et al, 1993), exhibit severe cerebellar symptoms such as ataxia and motor discoordination and lack LTD (Aiba et al, 1994;Conquet et al, 1994). The behavioral relevance of Purkinje cell mGluR1 for proper cerebellar function was elegantly and unequivocally confirmed by the selective rescue of mGluRs in Purkinje cells of mGluR1 null mutant mice (Ichise et al, 2000), which restored both LTD and locomotor activity.…”

Section: Introductionmentioning

confidence: 99%

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Calbindin in Cerebellar Purkinje Cells Is a Critical Determinant of the Precision of Motor Coordination

et al. 2003

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Section: Ltd At the Parallel Fiber 3 Purkinje Cell Synapsesupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Calbindin in Cerebellar Purkinje Cells Is a Critical Determinant of the Precision of Motor Coordination

et al. 2003

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“…Recently, data from genetic knock-out experiments have distinguished between mGluRs 1 and 5 in cerebellar function. Mice deficient in mGluR1 show severe motor coordination problems and ataxia (Aiba et al, 1994;Conquet et al, 1994), whereas motor coordination appears normal in mice lacking mGluR5 (Wojtowicz et al, 1996). Basal ganglia function in these knock-out mice has not been examined as yet.…”

Section: Discussionmentioning

confidence: 99%

Metabotropic Glutamate Agonist-Induced Rotation: A Pharmacological, FOS Immunohistochemical, and [¹⁴C]-2-Deoxyglucose Autoradiographic Study

1997

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Metabotropic glutamate receptors (mGluRs) are a major class of excitatory amino acid receptors. Eight mGluR subtypes, coupled to a variety of effector systems, have been cloned. These receptors have been classified into three groups based on amino acid sequence homology, effector systems, and pharmacological profile. Group I mGluRs increase phosphoinositide turnover, whereas groups II and III mGluRs are negatively coupled to adenylyl cyclase. The striatum possesses a high density of mGluR binding sites, and several mGluR mRNAs and proteins are expressed by striatal neurons. In rats, unilateral striatal injection of the nonsubtype selective mGluR agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid (1S,3R-ACPD) results in contralateral rotation with delayed onset, thought to be secondary to an increase in dopamine release. We sought to determine the mGluR subtype(s) involved, the modulation of the rotation by other basal ganglia neurotransmitter systems, and the functional anatomy underlying the rotational behavior. The group I mGluR agonist 3,5-dihydroxyphenylglycine (DHPG) induced contralateral rotation in a dose-dependent manner, whereas group II and group III agonists were ineffective. Rotation induced by DHPG or 1S,3R-ACPD was attenuated by group I antagonists, but not by group II or group III antagonists. This suggests that the rotation is mediated by group I mGluRs. Rotation induced by DHPG or 1S,3R-ACPD was attenuated by pretreatment with antagonists at muscarinic cholinergic, adenosine A 2 , dopamine D 2 , or dopamine D 1 receptors. Examination of FOS-like immunoreactivity after group I and group II mGluR agonist administration suggests increased activity in the striatopallidal pathway. However, [ 14 C]-2-deoxyglucose uptake studies indicate increased activity in nuclei of the striatopallidal (indirect) pathway, particularly in the subthalamic nucleus, only after group I mGluR activation. Key words: metabotropic glutamate receptor; basal ganglia; subthalamic nucleus; striatum; dopamine; adenosine A2 receptors; muscarinic receptorsExcitatory amino acids (EAAs) are important neurotransmitters in the basal ganglia, and EAAergic agents are being investigated actively as possible pharmacotherapies for basal ganglia disorders. A major class of EAA receptors are the metabotropic glutamate receptors (mGluRs), coupled to second messenger systems via G-proteins. Eight mGluR subtypes have been cloned, several of which possess splice variants. These mGluR subtypes have been categorized into three groups based on their amino acid sequence homology, effector systems, and pharmacological profile. When expressed and activated in transfection systems, group I receptors (mGluRs 1 and 5) stimulate phosphoinositide hydrolysis. Group II (mGluRs 2 and 3) and group III (mGluRs 4 -8) receptors inhibit adenylyl cyclase, although with different pharmacological profiles (for review, see Pin and Duvosin, 1995;Roberts, 1995). Ligand-binding studies have shown the striatum to possess a high density of mGluR binding sites (Albin et al....

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“…Such mutants may be valuable tools to study in vivo roles particular genes may play in the mammalian central nervous system (CNS) [25]. Metabotropic and ionotropic glutamate receptors have recently become a target of molecular genetic studies [1,12,31,50,53,34,7] since glutamate is one of the major excitatory neurotransmitters of the CNS and its receptors are postulated to play roles in neural plasticity [7,47,50]. A subclass of glutamate receptors (GluR1, 2, 3, and 4) is defined by their high affinity for h-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA) but low affinity for kainate [28].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, a higher elevation of intracellular Ca 2 + levels is associated with LTP and a smaller increase of Ca 2 + is seen when long-term depression (LTD) is induced [3,41]. LTD is known to play a prominent role not only in the hippocampus but also in the cerebellum where it is thought to be involved in motor learning and in the fine tuning of motor responses [1,30,39,40]. Because changes in Ca 2 + permeability in GluR2 null mutant mice [31] may alter synaptic processes including LTP and LTD, the mutants may posses functional abnormalities that involve several brain regions.…”

Section: Introductionmentioning

confidence: 99%

Multiple behavioral anomalies in GluR2 mutant mice exhibiting enhanced LTP

Gerlai

Henderson

Roder

et al. 1998

Behavioural Brain Research

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Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice

Cited by 749 publications

References 65 publications

Calbindin in Cerebellar Purkinje Cells Is a Critical Determinant of the Precision of Motor Coordination

Calbindin in Cerebellar Purkinje Cells Is a Critical Determinant of the Precision of Motor Coordination

Metabotropic Glutamate Agonist-Induced Rotation: A Pharmacological, FOS Immunohistochemical, and [¹⁴C]-2-Deoxyglucose Autoradiographic Study

Multiple behavioral anomalies in GluR2 mutant mice exhibiting enhanced LTP

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Deficient cerebellar long-term depression and impaired motor learning in mGluR1 mutant mice

Cited by 749 publications

References 65 publications

Calbindin in Cerebellar Purkinje Cells Is a Critical Determinant of the Precision of Motor Coordination

Calbindin in Cerebellar Purkinje Cells Is a Critical Determinant of the Precision of Motor Coordination

Metabotropic Glutamate Agonist-Induced Rotation: A Pharmacological, FOS Immunohistochemical, and [14C]-2-Deoxyglucose Autoradiographic Study

Multiple behavioral anomalies in GluR2 mutant mice exhibiting enhanced LTP

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Metabotropic Glutamate Agonist-Induced Rotation: A Pharmacological, FOS Immunohistochemical, and [¹⁴C]-2-Deoxyglucose Autoradiographic Study