The thalamostriatal systems: anatomical and functional organization in normal and parkinsonian states

Abstract

Although we have gained significant knowledge in the anatomy and microcircuitry of the thalamostriatal system over the last decades, the exact function(s) of these complex networks remain(s) poorly understood. It is now clear that the thalamostriatal system is not a unique entity, but consists of multiple neural systems that originate from a wide variety of thalamic nuclei and terminate in functionally segregated striatal territories. The primary source of thalamostriatal projections is the caudal intralaminar nuclear group which, in primates, comprises the centromedian and parafascicular nuclei (CM/Pf). These two nuclei provide massive, functionally organized glutamatergic inputs to the whole striatal complex. There are several anatomical and physiological features that distinguish this system from other thalamostriatal projections. Although all glutamatergic thalamostriatal neurons express vGluT2 and release glutamate as neurotransmitter, CM/Pf neurons target preferentially the dendritic shafts of striatal projection neurons, whereas all other thalamic inputs are almost exclusively confined to the head of dendritic spines. This anatomic arrangement suggests that transmission of input from sources other than CM/Pf to the striatal neurons is likely regulated by dopaminergic afferents in the same manner as cortical inputs, while the CM/Pf axo-dendritic synapses do not display any particular relationships with dopaminergic terminals. A better understanding of the role of these systems in the functional circuitry of the basal ganglia relies on future research of the physiology and pathophysiology of these networks in normal and pathological basal ganglia conditions. Although much remains to be known about the role of these systems, recent electrophysiological studies from awake monkeys have provided convincing evidence that the CM/Pf-striatal system is the entrance for attention-related stimuli to the basal ganglia circuits. However, the processing and transmission of this information likely involves intrinsic GABAergic and cholinergic striatal networks, thereby setting the stage for complex physiological responses of striatal output neurons to CM/Pf activation. Finally, another exciting development that will surely generate significant interest towards the thalamostriatal systems in years to come is the possibility that CM/Pf may be a potential surgical target for movement disorders, most particularly Tourette syndrome and Parkinson's disease. Although the available clinical evidence is encouraging, these procedures remain empirical at this stage because of the limited understanding of the thalamostriatal systems.

Figure 1

Color-coded summary of the various sub-compartments of the CM/PF complex with their main striatal-receiving territories in monkeys. The antero-posterior stereotaxic coordinates of the striatal and CM/PF sections are indicated. The lateral part of CM (CMl) projects preferentially to the primary motor cortex, while other areas are connected with specific striatal regions. Via these specific thalamostriatal connections, the information flows through segregated motor, associative and limbic basal gangliathalamostriatal loops that involve various regions of the striatum, GPi/SNr and CM/PF. [See references ,, for more details]

Figure 2

Summary of the general pattern of CM inputs to the striatum and the cerebral cortex. Although a significant proportion of single CM neurons innervate both regions, CM-striatal projections are more massive and give rise to more profuse and focussed fields of terminals than the sparse CM-cortical axons that innervate motor cortices (See references , for more details].

Figure 3

Summary of results from anterograde tracing studies of thalamic projections to the rat striatum. The histogram illustrates the percentage of labeled boutons from each of the thalamic or cortical (M1) regions injected. Apart from Pf, all other thalamic nuclei and M1 give rise to terminals that contact almost exclusively dendritic spines in the rat striatum. These findings are summarized on the model of striatal medium spiny neuron on the right. Abbreviations: AV: Anteroventral nucleus, CL: Centrolateral nucleus, LD: Laterodorsal nucleus, MD: Mediodorsal nucleus, M1: Primary motor cortex, PF: Parafascicular nucleus, VA/VL: Ventral anterior/ventral lateral nucleus. [See references and for more details].

Figure 4

Responses of striatal neurons to CM stimulation. (A-C) Peri-stimulus raster and rate diagrams of two MSNs (called PANs, A, B) and one interneuron (called TANs, C), in response to CM stimulation. Stimuli were applied at 100 Hz, during the shaded period. Stimulation trains were aligned to the onset of the first pulse (time = 0). In the rate diagrams, the dashed horizontal lines show the median and the 22nd and 78th percentiles. (D-E) Distribution of responses of striatal MSNs (D; n=22) and interneurons (E; n=21) to CM nucleus stimulation. [See reference 64b for more details].