Glutamatergic pallidothalamic projections and their implications in the pathophysiology of Parkinson's disease.
GABAergic projections emitted from the entopeduncular nucleus (ENT) and the substantia nigra pars reticulata (SNr) innervate different thalamic nuclei and they are known to be hyperactive after dopaminergic depletion. Here we show that isoform 2 of the vesicular glutamate transporter (VGLUT2) is expressed by neurons in the ENT nucleus but not in the SNr. Indeed, dual in situ hybridization demonstrated that the ENT nucleus contains two different subpopulations of projection neurons, one single-expressing GAD65/67 mRNAs and another one that co-expresses either of the GAD isoforms together with VGLUT2 mRNA. Unilateral dopaminergic depletion induced marked changes in pallidothalamic-projecting neuron gene expression, resulting in increased expression of GAD65/67 mRNAs together with a clear down-regulation of VGLUT2 mRNA expression. Our results indicate that the increased thalamic inhibition typical of dopamine depletion might be explained by a synergistic effect of increased GABA outflow coupled to decreased glutamate levels, both neurotransmitters coming from ENT neurons.
Barroso-Chinea
Pedro
P
Area de Neurociencias, Centro de Investigación Médica Aplicada (CIMA) and Centro de Investigación en Red de Enfermedades Neurodegenerativas (CIBERNED), Facultad de Medicina, Universidad de Navarra, Spain.
Rico
Alberto J
AJ
Pérez-Manso
Mónica
M
Roda
Elvira
E
López
Iciar P
IP
Luis-Ravelo
Diego
D
Lanciego
José L
JL
D000818:Animals; D004298:Dopamine / Q000172:deficiency; D015536:Down-Regulation / Q000502:physiology; D004525:Efferent Pathways / Q000378:metabolism / Q000503:physiopathology; D020392:Entopeduncular Nucleus / Q000378:metabolism / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D005917:Globus Pallidus / Q000378:metabolism* / Q000503:physiopathology; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D020734:Parkinsonian Disorders / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000378:metabolism / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology; D013788:Thalamus / Q000378:metabolism* / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology; D050599:Vesicular Glutamate Transport Protein 2 / Q000235:genetics / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D012333:RNA, Messenger; C493475:Slc17a6 protein, rat; D050599:Vesicular Glutamate Transport Protein 2; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2; D004298:Dopamine