The basal ganglia have become a focus for work on neurotransmitter interactions in the brain. These structures contain a remarkable diversity of neuroactive substances, organized into functional subsystems that have unique developmental histories and vulnerabilities in neurodegenerative diseases. A new view of the basal ganglia is emerging on the basis of this neurochemical heterogeneity, suggesting that dynamic regulation of transmitter expression may be a key to extrapyramidal function.

Together with the internal segment of the globus pallidus (GP(i)), 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.

The selection and execution of appropriate motor behavior result in large part from the ability of the basal ganglia to collect, integrate and feedback information coming from the cerebral cortex. The GABAergic medium spiny neurons (MSNs) of the striatum represent the main receiving station of the basal ganglia. These cells are innervated by excitatory glutamatergic fibers from cortex and thalamus, and modulatory dopaminergic fibers from the midbrain. MSNs comprise two populations of projection neurons, which give rise to the direct, striatonigral pathway, and indirect, striatopallidal pathway. Changes in transmission at the level MSNs affect the activity of thalamocortical projection neurons, thereby influencing motor behavior. For instance, the cardinal symptoms of Parkinson?s disease, such as tremor, rigidity and bradykinesia, are caused by the selective degeneration of dopaminergic neurons originating in the substantia nigra pars compacta, which modulate the activity of MSNs in the dorsal striatum. The therapy for Parkinson?s disease relies on the use of levodopa, but is hampered by neuroadaptive changes affecting dopaminergic and glutamatergic transmission in striatonigral neurons. MSNs are also the target of many psychoactive drugs. For example, caffeine affects motor activity by blocking adenosine receptors in the basal ganglia, thereby affecting neurotransmission in striatopallidal neurons. The present review focuses on studies performed in our laboratory, which provide a molecular framework to understand the effects on motor activity of adenosine and caffeine.

We present a biologically plausible model of processing intrinsic to the basal ganglia based on the computational premise that action selection is a primary role of these central brain structures. By encoding the propensity for selecting a given action in a scalar value (the salience), it is shown that action selection may be recast in terms of signal selection. The generic properties of signal selection are defined and neural networks for this type of computation examined. A comparison between these networks and basal ganglia anatomy leads to a novel functional decomposition of the basal ganglia architecture into ?selection? and ?control? pathways. The former pathway performs the selection per se via a feedforward off-centre on-surround network. The control pathway regulates the action of the selection pathway to ensure its effective operation, and synergistically complements its dopaminergic modulation. The model contrasts with the prevailing functional segregation of basal ganglia into ?direct? and ?indirect? pathways.

The majority of neurons in the basal ganglia utilize GABA as their principal neurotransmitter and, as a consequence, most basal ganglia neurons receive extensive GABAergic inputs derived from multiple sources. In order to understand the diverse roles of GABA in the basal ganglia it is necessary to define the precise localization of GABA receptors in relation to known neuron subtypes and known afferents. In this chapter, we summarize data on the ultrastructural localization of ionotropic GABA(A) receptors and metabotropic GABA(B) receptors in the basal ganglia. In each of the regions of the basal ganglia that have been studied, GABA(A) receptor subunits are located primarily at symmetrical synapses formed by GABAergic boutons, where they display a several-hundred-fold enrichment over extrasynaptic sites. In contrast, GABA(B) receptors are widely distributed at synaptic and extrasynaptic sites on both presynaptic and postsynaptic membranes. Presynaptic GABA(B) receptors are localized on striatopallidal, striatonigral and pallidonigral afferent terminals, as well as glutamatergic terminals derived from the cortex, thalamus and subthalamic nucleus. It is concluded that fast GABA transmission mediated by GABA(A) receptors in the basal ganglia occurs primarily at synapses whereas GABA transmission mediated by GABA(B) receptors is more complex, involving receptors located at presynaptic, postsynaptic and extrasynaptic sites.

excellente revue!! indispensable