Dichotomous Organization of the External Globus Pallidus

Abstract

SummaryDifferent striatal projection neurons are the origin of a dual organization essential for basal ganglia function. We have defined an analogous division of labor in the external globus pallidus (GPe) of Parkinsonian rats, showing that the distinct temporal activities of two populations of GPe neuron in vivo are underpinned by distinct molecular profiles and axonal connectivities. A first population of prototypic GABAergic GPe neurons fire antiphase to subthalamic nucleus (STN) neurons, often express parvalbumin, and target downstream basal ganglia nuclei, including STN. In contrast, a second population (arkypallidal neurons) fire in-phase with STN neurons, express preproenkephalin, and only innervate the striatum. This novel cell type provides the largest extrinsic GABAergic innervation of striatum, targeting both projection neurons and interneurons. We conclude that GPe exhibits several core components of a dichotomous organization as fundamental as that in striatum. Thus, two populations of GPe neuron together orchestrate activities across all basal ganglia nuclei in a cell-type-specific manner.

Therapeutic mechanisms of high-frequency stimulation in Parkinson’s disease and neural restoration via loop-based reinforcement

“…8) which, for these neurons, resulted independent of the specific prestimulation activity. Finally, there is evidence in NHPs and rats of GABAergic projections from the GPe to the motor striatum (93,94). Although numerically limited, these projections have diffusive organization in the striatum and might determine a strong, DBSlocked inhibitory input to the striatal neurons, as recently proposed (95).…”

Die Rolle der Basalganglien beim Unterdrücken von Handlungsimpulsen

“…Beginnen wir mit dem subthalamischen Nukleus (STN) -einer sehr kleinen Region, die unter anderem bei der Parkinson-Krankheit eine wichtige Rolle spielt. Hier haben wir Neurone gefunden, die auf das Stop-Signal mit einer Erhöhung der "Feuerrate" (Anzahl der Aktionspotentiale pro Sekunde) reagieren (Abbildung 2A; Schmidt et al 2013 Schmidt et al 2013;B und C auf Mallet et al 2016 (Mallet et al 2012). Dies sind ideale Voraussetzungen für eine umfassende Unterdrückung von Go-Signalen.…”

“…Die "normalen" Neurone (sogenannte prototypische Neurone) projizieren in den STN und in die SNr (Abbildung 1A). Die kürzlich entdeckten, sogenannten arkypallidalen Neurone projizieren hingegen nur ins Striatum (Mallet et al 2012). Woher wissen wir aber, zu welchem Typ eine gemessene Zelle gehört?…”

Do gap junctions regulate synchrony in the Parkinsonian basal ganglia?

“…The second population described a novel cell type: neurons that fired in-phase with STN neurons expressed proenkephalin and innervated both projection neurons and interneurons of the striatum. Mallet et al [2012] also found differences in the dendritic and axonal architectures of the two cell types. In particular, local axon collaterals of the first neural population were longer while their dendritic spine density was lower in comparison to the second population.…”

“…Based on fate mapping analysis, even five neural populations have been identified in the mouse GP which differ in progenitor lineage and partly in their embryonic domains [Nobrega-Pereira et al, 2010]. Recently, Mallet et al [2012] combined anatomical and electrophysiological characteristics of classes of GP neurons. They described the existence of two distinct neural populations in the GP of a 6-OHDA treated rat that have distinct molecular profiles and axonal connectivities.…”