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Article: Cerebellar vascular and synaptic responses in normal mice and in transgenics with Purkinje cell dysfunction

TitleCerebellar vascular and synaptic responses in normal mice and in transgenics with Purkinje cell dysfunction
Authors
KeywordsCerebellum
Cerebral Circulation
Glutamate
Laser-Doppler Flowmetry
Vasodilation
Issue Date1998
PublisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpregu.physiology.org
Citation
American Journal Of Physiology - Regulatory Integrative And Comparative Physiology, 1998, v. 274 n. 2 43-2, p. R529-R540 How to Cite?
AbstractWe used transgenic mice with Purkinje cell dysfunction (PO3 line) to study the role of these neurons in the increase in cerebellar blood flow (BF(crb)) produced by stimulation of the cerebellar parallel fibers (PF). Mice (age 8-10 wk) were anesthetized (halothane) and artificially ventilated. Arterial pressure and end-tidal CO 2 were monitored continuously. Arterial blood gases were measured. The PF were stimulated electrically (100 μA, 30 Hz; 40 s), and the increases in BF(crb) were monitored by a laser-Doppler flow probe. First, we characterized the increases in BF(crb) and the field potentials produced by PF stimulation in normal mice. PF stimulation evoked the typical field potentials and increased BF(crb) by 60 ± 4% (100 μA, 30 Hz; n = 10). The increases in BF(crb) were attenuated by the broad-spectrum glutamate receptor antagonist kynurenate (-84 ± 3%; P < 0.05 analysis of variance; n = 5), by the DL-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl- benzo(f)quinoxaline (-62 ± 6%; P < 0.05; n = 5), and by the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine (-46 ± 7%; P < 0.05; n = 5). In PO3 transgenic mice, the increases in BF(crb) produced by PF stimulation were reduced (P < 0.001) at every stimulus intensity and frequency tested (residual increase at 100 μA, 30 Hz: 19 ± 2%; n = 6). The field potentials evoked by PF stimulation also were abnormal in that they lacked the late negative wave (n = 6), a finding consistent with lack of depolarization of Purkinje cells. The residual flow response in the transgenics was abolished by N(ω)-nitro-L-arginine (n = 5; P > 0.05). Ultrastructural studies showed that the density of PF-Purkinje cell synapses is reduced in PO3 mice, whereas the morphology of molecular layer interneurons (stellate cells) is normal. The findings suggest that Purkinje cells are responsible for a sizable component of the flow response whereas molecular layer interneurons mediate the remainder of the response. The study provides evidence that mouse mutants with spontaneous or genetically engineered cerebellar abnormalities could be useful to study the cellular and molecular correlates of functional hyperemia in the central nervous system.
Persistent Identifierhttp://hdl.handle.net/10722/174754
ISSN
2015 Impact Factor: 3.168
2015 SCImago Journal Rankings: 1.663
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYang, Gen_US
dc.contributor.authorFeddersen, RMen_US
dc.contributor.authorZhang, Fen_US
dc.contributor.authorClark, HBen_US
dc.contributor.authorBeitz, AJen_US
dc.contributor.authorIadecola, Cen_US
dc.date.accessioned2012-11-26T08:47:16Z-
dc.date.available2012-11-26T08:47:16Z-
dc.date.issued1998en_US
dc.identifier.citationAmerican Journal Of Physiology - Regulatory Integrative And Comparative Physiology, 1998, v. 274 n. 2 43-2, p. R529-R540en_US
dc.identifier.issn0363-6119en_US
dc.identifier.urihttp://hdl.handle.net/10722/174754-
dc.description.abstractWe used transgenic mice with Purkinje cell dysfunction (PO3 line) to study the role of these neurons in the increase in cerebellar blood flow (BF(crb)) produced by stimulation of the cerebellar parallel fibers (PF). Mice (age 8-10 wk) were anesthetized (halothane) and artificially ventilated. Arterial pressure and end-tidal CO 2 were monitored continuously. Arterial blood gases were measured. The PF were stimulated electrically (100 μA, 30 Hz; 40 s), and the increases in BF(crb) were monitored by a laser-Doppler flow probe. First, we characterized the increases in BF(crb) and the field potentials produced by PF stimulation in normal mice. PF stimulation evoked the typical field potentials and increased BF(crb) by 60 ± 4% (100 μA, 30 Hz; n = 10). The increases in BF(crb) were attenuated by the broad-spectrum glutamate receptor antagonist kynurenate (-84 ± 3%; P < 0.05 analysis of variance; n = 5), by the DL-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl- benzo(f)quinoxaline (-62 ± 6%; P < 0.05; n = 5), and by the nitric oxide synthase inhibitor N(ω)-nitro-L-arginine (-46 ± 7%; P < 0.05; n = 5). In PO3 transgenic mice, the increases in BF(crb) produced by PF stimulation were reduced (P < 0.001) at every stimulus intensity and frequency tested (residual increase at 100 μA, 30 Hz: 19 ± 2%; n = 6). The field potentials evoked by PF stimulation also were abnormal in that they lacked the late negative wave (n = 6), a finding consistent with lack of depolarization of Purkinje cells. The residual flow response in the transgenics was abolished by N(ω)-nitro-L-arginine (n = 5; P > 0.05). Ultrastructural studies showed that the density of PF-Purkinje cell synapses is reduced in PO3 mice, whereas the morphology of molecular layer interneurons (stellate cells) is normal. The findings suggest that Purkinje cells are responsible for a sizable component of the flow response whereas molecular layer interneurons mediate the remainder of the response. The study provides evidence that mouse mutants with spontaneous or genetically engineered cerebellar abnormalities could be useful to study the cellular and molecular correlates of functional hyperemia in the central nervous system.en_US
dc.languageengen_US
dc.publisherAmerican Physiological Society. The Journal's web site is located at http://intl-ajpregu.physiology.orgen_US
dc.relation.ispartofAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiologyen_US
dc.subjectCerebellumen_US
dc.subjectCerebral Circulationen_US
dc.subjectGlutamateen_US
dc.subjectLaser-Doppler Flowmetryen_US
dc.subjectVasodilationen_US
dc.titleCerebellar vascular and synaptic responses in normal mice and in transgenics with Purkinje cell dysfunctionen_US
dc.typeArticleen_US
dc.identifier.emailZhang, F: fuchun@hkucc.hku.hken_US
dc.identifier.authorityZhang, F=rp00840en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid9486314-
dc.identifier.scopuseid_2-s2.0-0031887524en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0031887524&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume274en_US
dc.identifier.issue2 43-2en_US
dc.identifier.spageR529en_US
dc.identifier.epageR540en_US
dc.identifier.isiWOS:000071968700034-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYang, G=55186713000en_US
dc.identifier.scopusauthoridFeddersen, RM=35594019800en_US
dc.identifier.scopusauthoridZhang, F=14012468800en_US
dc.identifier.scopusauthoridClark, HB=7202405689en_US
dc.identifier.scopusauthoridBeitz, AJ=7005732161en_US
dc.identifier.scopusauthoridIadecola, C=7006626243en_US

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