The pars reticulata of the substantia nigra: a window to basal ganglia output

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Abstract

Together with the internal segment of the globus pallidus (GPi), the pars reticulata of the substantia nigra (SNr) provides a main output nucleus of the basal ganglia (BG) where the final stage of information processing within this system takes place. In the last decade, progress on the anatomical organization and functional properties of BG output neurons have shed some light on the mechanisms of integration taking place in these nuclei and leading to normal and pathological BG outflow. In this review focused on the SNr, after describing how the anatomical arrangement of nigral cells and their afferents determines specific input–output registers, we examine how the basic electrophysiological properties of the cells and their interaction with synaptic inputs contribute to the spatio-temporal shaping of BG output. The reported data show that the intrinsic membrane properties of the neurons subserves a tonic discharge allowing BG to gate the transmission of information to motor and cognitive systems thereby contributing to appropriate selection of behavior.

Section snippets

Neuronal types

Compared to the overlying cell rich pars compacta, the SNr is characterized by a low neuronal density, the cells being interspaced within a dense neuropil of radiating dendrites issued from both the SNr and SNc neurons. Laterally, the SNr merges within the substantia nigra pars lateralis (SNl), a cluster of cells considered as a lateral extension of the SN where SNr and SNc neurons intermingle. The SNr is essentially composed of projection neurons. These cells have been characterized in

Cytoarchitecture and functional compartmentalization

Information from virtually the entire cerebral cortex is transmitted to the SNr via the striatonigral projections (McGeorge and Faull, 1989; Deniau et al., 1996; and see for review: Alexander et al., 1986; Groenewegen and Berendse, 1994; Parent and Hazrati, 1995a; Deniau and Thierry, 1997; Smith et al., 1998; Haber, 2003). Evidence that the topographic arrangement of the cortico-striatal projection imposes to the striatum a rigorous functional compartmentalization led to investigations of

Functional properties of SNr cells

The GABAergic output neurons of the SNr exhibit electrophysiological properties clearly distinct from those of the DA nigral neurons. Contrasting with the large action potentials, low-frequency firing rate and strong spike accommodation of the DA nigrostriatal neurons, the GABAergic nigrothalamic, nigrocollicular and nigrotegmental neurons are characterized by short-duration action potentials, a spontaneous repetitive firing reaching 40–80 Hz in vivo and an ability to generate high-frequency

The striatonigral input

Medium-sized spiny neurons, the main neuronal population of striatum, provide a major source of GABAergic inputs to SNr neurons (see for review Dray, 1979; Graybiel and Ragsdale, 1979; Graybiel, 1984; McGeer et al., 1984; Smith and Bolam, 1990a, Smith and Bolam, 1990b; Langer et al., 1991; Parent and Hazrati, 1995a; Smith et al., 1998; Bolam et al., 2000). The dendrites of nigrothalamic and nigrotegmental neurons are ensheathed by the terminal boutons of striatal fibers that form symmetrical

The pallidonigral input

Besides the striatum, the GPe provides an additional source of GABAergic inputs to the SNr (McBride and Larsen, 1980; Parent and De Bellefeuille, 1983; Smith and Bolam, 1989; Von Krosigk et al., 1992; Bevan et al., 1996; Shink et al., 1996). As shown in rodent, this projection arises from the subpopulations of pallidal neurons belonging to the categories of aspiny and spiny neurons located mainly in the lateral part of the GPe (Totterdell et al., 1984; Smith and Bolam, 1989; Kita and Kitai, 1994

The subthalamonigral input

The STN is the only glutamatergic component of the BG and provides the main source of glutamatergic inputs to BG output nuclei (see for review Parent and Hazrati, 1995b; Smith et al., 1998). In rodent, the STN projection to the SNr originates from the whole nucleus, with most STN neurons sending branched axons to GPe, entopeduncular nucleus (EN) and SNr (Deniau et al., 1978a, Deniau et al., 1978b; Van Der Kooy and Hattori, 1980). In primates, retrograde labeling studies have suggested that the

Local interactions between SNr cells

SNr projection neurons possess a recurrent axon collateral network through which these cells are engaged in mutual inhibitory interactions. The spatial arrangement of this local axonal network has been precisely determined in the rat using single cell labeling and 3D reconstructions (Mailly et al., 2003). Despite important variability, some general rules could be drawn from the axonal population studied. The trajectories of axons largely conform to the lamellar architecture of the SNr. They

Regulation by neuromodulators

Various peptides (tachykinins, dynorphin, enkephalin, neurotensin, secretoneurin, orexin, cholecystokinin, neuropeptides K and Y, Nociceptin/orphanin), endocannabinoids and neuromodulators can influence SNr cells discharge either directly or indirectly via a presynaptic control of GABAergic and glutamatergic transmissions (Graybiel, 1986; Lavin and Garcia-Munoz, 1986; Valentino et al., 1986; Robertson et al., 1987; Hokfelt et al., 1991; Martin et al., 1991; Castel et al., 1993; Zhang and

Conclusion and perspectives

As an output nucleus of the BG, the SNr exerts major functions. Thanks to their ability to generate repetitive discharges, SNr neurons gate the transmission of information to motor and cognitive systems thereby contributing to the selection of behavior, and through the arrest of their discharge favors behavioral output (Redgrave et al., 1999; Gurney et al., 2001). The role of the SNr however cannot be restricted to a simple steering mechanism based upon simple inhibitory-disinhibitory

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