Striatal Information Signaling and Integration in Globus Pallidus: Timing Matters

Abstract

Advances in research on globus pallidus (GP) suggest that this ‘long thought to be’ relay in the ‘indirect pathway’ plays a unique and critical role in basal ganglia function. The traditional idea of parallel processing within the basal ganglia is also challenged by recent findings. It is now clear that axons of GP neurons form large, perisomatic baskets around target neurons in all major basal ganglia nuclei, thereby exerting a profound influence on the output of the entire basal ganglia. GP neurons are autonomously active both in vivo and in vitro. It is believed that temporal information carried along the corticostriatopallidal pathway is critical for proper motor execution. The importance of appropriately controlled discharge of GP neurons is highlighted by psychomotor disorders such as Parkinson’s disease, in which alterations in the pattern and synchrony of discharge in GP neurons are thought to contribute to motor symptoms. Several lines of evidence suggest that the aberrant activity of GP neurons following dopamine depletion is caused by alteration in the synaptic input from both striatum and subthalamic nucleus. In normal subjects, the capability of striatal input in translating cortical input into precisely timed responses in GP neurons is mediated by (1) the expression of postsynaptic GABA_A receptor composed of subunits with fast kinetic properties; (2) an effective GABA reuptake system in terminating the action of synaptically released GABA, and (3) the existence of dendritic HCN channels that actively abbreviate the time course of the inhibitory postsynaptic potentials and reset rhythmic discharge. Despite the rapid pace in uncovering the elements that shape the activity along the striatopallidosubthalamic pathway, the origin of rhythmic, synchronized bursting of GP neurons seen in parkinsonism has not been fully established experimentally. Further elucidation of the factors that control the information transfer in the striatopallidal synapses is thus critical to our understanding of basal ganglia function and establishing treatment for Parkinson’s disease and other basal ganglia disorders.

Concurrent activation of striatal direct and indirect pathways during action initiation

“…Finally, we showed that activity in both pathways predicted the occurrence of specific movements within 500 ms of transient initiation. While these data do not support a prokinetic/antikinetic dichotomy in direct versus indirect pathways, they are consistent with other models postulating that the coordinated activation of both pathways is important for action selection, or for precise timing of basal ganglia output 12,13,24 .…”

“…Some propose, for example, that activation of the direct pathway could facilitate output of the desired motor programs while activation of the indirect pathway would inhibit competing motor programs 3,4,11 . Others suggest that coordinated activity of direct and indirect pathway is critical for the appropriate timing/synchrony of basal ganglia circuits during movement 12,13 .…”

Dopamine systems adaptation during acquisition and consolidation of a skill

“…The basal ganglia motor circuitry is essential in controlling voluntary movements whereby the direct D1 pathway is typically seen as the driver, while the indirect D2 pathway was ascribed the role of the break, together ensuring the fine tuning of intentional motor activity (Albin et al, 1989; Alexander and Crutcher, 1990; Sommer et al, 1996; Gerfen and Surmeier, 2011). Although this dichotomous model is still under discussion (Cui et al, 2013), coordinated activity in both pathways is essential for proper action selection and execution (Chan et al, 2005; Brown, 2007; Gremel and Costa, 2013). …”

Muscarinic presynaptic modulation in GABAergic pallidal synapses of the rat

“…Str afferents are abundant (Schwab et al 2013). All these connections suggest that the GPe is an important integrative center, not just a relay nucleus (Chan and Surmeier 2005;Goldberg and Bergman 2011;Kita 2007;Mena-Segovia et al 2004;Schwab et al 2013).…”

“…If these hypotheses were proven, a function for cholinergic innervation to the GPe would have been disclosed (Gorbachevskaya and Chivileva 2006;Woolf and Butcher 1986). Cholinergic fibers from the PPN innervate the telencephalon and diverse basal ganglia nuclei, including the GPe (Chan and Surmeier 2005;Charara and Parent 1994;MenaSegovia et al 2004). In addition, the GPe may have local cholinergic neurons (Rodrigo et al 1998) and perhaps receive cholinergic innervation coming from the ventral pallidum (Bengtson and Osborne 2000).…”