Document Detail


Developmental enhancement of alpha2-adrenoceptor-mediated suppression of inhibitory synaptic transmission onto mouse cerebellar Purkinje cells.
MedLine Citation:
PMID:  18691636     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Noradrenaline (NA) modulates glutamatergic and GABAergic transmission in various areas of the brain. It is reported that some alpha2-adrenoceptor subtypes are expressed in the cerebellar cortex and alpha2-adrenoceptors may play a role in motor coordination. Our previous study demonstrated that the selective alpha2-adrenoceptor agonist clonidine partially depresses spontaneous inhibitory postsynaptic currents (sIPSCs) in mouse cerebellar Purkinje cells (PCs). Here we found that the inhibitory effect of clonidine on sIPSCs was enhanced during postnatal development. The activation of alpha2-adrenoceptors by clonidine did not affect sIPSCs in PCs at postnatal days (P) 8-10, when PCs showed a few sIPSCs and interneurons in the molecular layer (MLIs) did not cause action potential (AP). In the second postnatal week, the frequency of sIPSCs increased temporarily and reached a plateau at P14. By contrast, MLIs began to fire at P11 with the firing rate gradually increasing thereafter and reaching a plateau at P21. In parallel with this rise in the rate of firing, the magnitude of the clonidine-mediated inhibition of sIPSCs increased during postnatal development. Furthermore, the magnitude of the clonidine-mediated firing suppression in MLIs, which seemed to be mediated by a reduction in amplitude of the hyperpolarization-activated nonselective cation current, I(h), was constant across development. Both alpha2A- and alpha2B-, but not alpha2C-, adrenoceptors were strongly expressed in MLIs at P13, and P31. Therefore, the developmental enhancement of the clonidine-mediated inhibition of sIPSCs is attributed to an age-dependent increase in AP-derived sIPSCs, which can be blocked by clonidine. Thus, presynaptic activation of alpha2-adrenoceptors inhibits cerebellar inhibitory synaptic transmission after the second postnatal week, leading to a restriction of NA signaling, which is mainly mediated by alpha1- and beta2-adrenoceptors in the adult cerebellar neuronal circuit.
Authors:
M Hirono; W Matsunaga; T Chimura; K Obata
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-18
Journal Detail:
Title:  Neuroscience     Volume:  156     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-09-15     Completed Date:  2009-01-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  143-54     Citation Subset:  IM    
Affiliation:
Neuronal Circuit Mechanisms Research Group, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. hironom@brain.riken.jp
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MeSH Terms
Descriptor/Qualifier:
Action Potentials / drug effects,  physiology
Adrenergic alpha-Agonists / pharmacology
Aging / physiology
Animals
Animals, Newborn
Cell Differentiation / physiology
Cerebellar Cortex / cytology,  growth & development*,  metabolism*
Clonidine / pharmacology
Female
Inhibitory Postsynaptic Potentials / drug effects,  physiology
Interneurons / drug effects,  metabolism
Male
Mice
Mice, Inbred C57BL
Neural Inhibition / drug effects,  physiology*
Norepinephrine / metabolism,  pharmacology
Organ Culture Techniques
Protein Isoforms / drug effects,  metabolism
Purkinje Cells / cytology,  drug effects,  metabolism*
Receptors, Adrenergic, alpha-2 / drug effects,  metabolism*
Synaptic Transmission / drug effects,  physiology*
Chemical
Reg. No./Substance:
0/Adrenergic alpha-Agonists; 0/Protein Isoforms; 0/Receptors, Adrenergic, alpha-2; 0/receptor, adrenergic, alpha-2A; 4205-90-7/Clonidine; 51-41-2/Norepinephrine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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