Dichotomous Organization of the External Globus Pallidus

Nicolas Mallet,Benjamin R Micklem,Pablo Henny,Matthew T Brown,Claire Williams,J Paul Bolam,Kouichi C Nakamura,Peter J Magill

doi:10.1016/j.neuron.2012.04.027

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.

Highlights

Functional dichotomy in striatal projection neurons is pivotal for the hugely influential ‘‘direct/indirect pathways’’ model of basal ganglia (BG) organization (Albin et al, 1989; Bergman et al, 1990; Gerfen and Surmeier, 2011; Smith et al, 1998; Wichmann and DeLong, 1996)
Physiological Dichotomy of External Globus Pallidus Neurons after Dopamine Loss To define the functional roles played by physiologically distinct GPe neurons in vivo, we electrophysiologically characterized and juxtacellularly labeled (Magill et al, 2001; Pinault, 1996) single units (n = 79) in the GPe of 6-OHDA-lesioned, anesthetized adult rats (n = 45)
We analyzed the action potential discharges of these identified GPe neurons during two spontaneous brain states as determined from simultaneously-recorded frontal electrocorticograms: (1) slow-wave activity (SWA), which is similar to activity observed during natural sleep; and (2) ‘‘activation,’’ which contains activity patterns more analogous to those observed during the awake, behaving state (Mallet et al, 2008a, 2008b)

Summary

Introduction

Functional dichotomy in striatal projection neurons is pivotal for the hugely influential ‘‘direct/indirect pathways’’ model of basal ganglia (BG) organization (Albin et al, 1989; Bergman et al, 1990; Gerfen and Surmeier, 2011; Smith et al, 1998; Wichmann and DeLong, 1996). Two major types of medium-sized denselyspiny neuron (MSN) preferentially innervate either external globus pallidus (GPe) or BG output nuclei (the internal globus pallidus, known as the entopeduncular nucleus [EPN] in rodents, and the substantia nigra pars reticulata [SNr]) They are further distinguished by distinct electrophysiological properties, selective expression of neuropeptides and dopamine receptors, and their opposing influences on behavior (Gerfen and Surmeier, 2011; Kravitz et al, 2010). Dopamine balances these two striatal outputs, and its loss in Parkinson’s disease (PD) promotes functional extremes, with disastrous behavioral consequences (Albin et al, 1989; Wichmann and DeLong, 1996). These models and concepts are idealized, such that they do not capture the full gamut of interactions of GPe or other BG nuclei (Bevan et al, 2002; Smith et al, 1998), they provide rationale for many pharmacological and surgical interventions in PD (Bergman et al, 1990; Schapira et al, 2006)

Results

Discussion

Conclusion