|
|
|
|
Elimination of the vesicular acetylcholine transporter in the striatum reveals regulation of behaviour by cholinergic-glutamatergic co-transmission
|
|
|
|
|
|
|
|
نویسنده
|
guzman m.s. ,de jaeger x. ,raulic s. ,souza i.a. ,li a.x. ,schmid s. ,menon r.s. ,gainetdinov r.r. ,caron m.g. ,bartha r. ,prado v.f. ,prado m.a.m.
|
|
منبع
|
plos biology - 2011 - دوره : 9 - شماره : 11
|
|
چکیده
|
Cholinergic neurons in the striatum are thought to play major regulatory functions in motor behaviour and reward. these neurons express two vesicular transporters that can load either acetylcholine or glutamate into synaptic vesicles. consequently cholinergic neurons can release both neurotransmitters,making it difficult to discern their individual contributions for the regulation of striatal functions. here we have dissected the specific roles of acetylcholine release for striatal-dependent behaviour in mice by selective elimination of the vesicular acetylcholine transporter (vacht) from striatal cholinergic neurons. analysis of several behavioural parameters indicates that elimination of vacht had only marginal consequences in striatum-related tasks and did not affect spontaneous locomotion,cocaine-induced hyperactivity,or its reward properties. however,dopaminergic sensitivity of medium spiny neurons (msn) and the behavioural outputs in response to direct dopaminergic agonists were enhanced,likely due to increased expression/function of dopamine receptors in the striatum. these observations indicate that previous functions attributed to striatal cholinergic neurons in spontaneous locomotor activity and in the rewarding responses to cocaine are mediated by glutamate and not by acetylcholine release. our experiments demonstrate how one population of neurons can use two distinct neurotransmitters to differentially regulate a given circuitry. the data also raise the possibility of using vacht as a target to boost dopaminergic function and decrease high striatal cholinergic activity,common neurochemical alterations in individuals affected with parkinson's disease. © 2011 guzman et al.
|
|
|
|
|
آدرس
|
molecular brain research group,robarts research institute,schulich school of medicine and dentistry,university of western ontario,london,on,canada,department of physiology and pharmacology,schulich school of medicine and dentistry,university of western ontario,london,on, Canada, molecular brain research group,robarts research institute,schulich school of medicine and dentistry,university of western ontario,london,on,canada,department of anatomy and cell biology,schulich school of medicine and dentistry,university of western ontario,london,on,canada,program in molecular pharmacology,faculty of medicine,federal university of minas gerais,belo horizonte,minas gerais, Brazil, molecular brain research group,robarts research institute,schulich school of medicine and dentistry,university of western ontario,london,on, Canada, molecular brain research group,robarts research institute,schulich school of medicine and dentistry,university of western ontario,london,on,canada,department of anatomy and cell biology,schulich school of medicine and dentistry,university of western ontario,london,on,canada,program in molecular pharmacology,faculty of medicine,federal university of minas gerais,belo horizonte,minas gerais, Brazil, imaging research group,robarts research institute,schulich school of medicine and dentistry,university of western ontario,london,on, Canada, department of anatomy and cell biology,schulich school of medicine and dentistry,university of western ontario,london,on, Canada, molecular brain research group,robarts research institute,schulich school of medicine and dentistry,university of western ontario,london,on,canada,imaging research group,robarts research institute,schulich school of medicine and dentistry,university of western ontario,london,on,canada,department of medical biophysics,schulich school of medicine and dentistry,university of western ontario,london,on, Canada, department of neuroscience and brain technologies,italian institute of technology,genova,italy,department of cell biology,duke university medical center,durham,nc, United States, department of cell biology,duke university medical center,durham,nc, United States, molecular brain research group,robarts research institute,schulich school of medicine and dentistry,university of western ontario,london,on,canada,imaging research group,robarts research institute,schulich school of medicine and dentistry,university of western ontario,london,on,canada,department of medical biophysics,schulich school of medicine and dentistry,university of western ontario,london,on, Canada, molecular brain research group,robarts research institute,schulich school of medicine and dentistry,university of western ontario,london,on,canada,department of physiology and pharmacology,schulich school of medicine and dentistry,university of western ontario,london,on,canada,department of anatomy and cell biology,schulich school of medicine and dentistry,university of western ontario,london,on, Canada, molecular brain research group,robarts research institute,schulich school of medicine and dentistry,university of western ontario,london,on,canada,department of physiology and pharmacology,schulich school of medicine and dentistry,university of western ontario,london,on,canada,department of anatomy and cell biology,schulich school of medicine and dentistry,university of western ontario,london,on, Canada
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|