The thalamostriatal system in normal and diseased states

Abstract

Because of our limited knowledge of the functional role of the thalamostriatal system, this massive network is often ignored in models of the pathophysiology of brain disorders of basal ganglia origin, such as Parkinson’s disease (PD). However, over the past decade, significant advances have led to a deeper understanding of the anatomical, electrophysiological, behavioral and pathological aspects of the thalamostriatal system. The cloning of the vesicular glutamate transporters 1 and 2 (vGluT1 and vGluT2) has provided powerful tools to differentiate thalamostriatal from corticostriatal glutamatergic terminals, allowing us to carry out comparative studies of the synaptology and plasticity of these two systems in normal and pathological conditions. Findings from these studies have led to the recognition of two thalamostriatal systems, based on their differential origin from the caudal intralaminar nuclear group, the center median/parafascicular (CM/Pf) complex, or other thalamic nuclei. The recent use of optogenetic methods supports this model of the organization of the thalamostriatal systems, showing differences in functionality and glutamate receptor localization at thalamostriatal synapses from Pf and other thalamic nuclei. At the functional level, evidence largely gathered from thalamic recordings in awake monkeys strongly suggests that the thalamostriatal system from the CM/Pf is involved in regulating alertness and switching behaviors. Importantly, there is evidence that the caudal intralaminar nuclei and their axonal projections to the striatum partly degenerate in PD and that CM/Pf deep brain stimulation (DBS) may be therapeutically useful in several movement disorders.

The neurobiology of thalamic amnesia: Contributions of medial thalamus and prefrontal cortex to delayed conditional discrimination

“…M and IL nuclei participate in cortico-thalamo-cortical pathways projecting widely to superficial layers of prefrontal, frontal, parietal, and medial temporal cortices regions as well as to anatomically related areas of the basal ganglia (Groenewegen and Berendse, 1994;Hoover and Vertes, 2012;Smith et al, 2014;Vertes et al, 2012). The broad effects of IL lesions seem consistent with these widely distributed modulatory projections.…”

Uncertainty and expectancy deviations require cortico-subcortical cooperation

“…Through the CM-Pf complex the thalamus sends functionally and topographically organized projections to the striatum Haber and Calzavara, 2009;Smith et al, 2004Smith et al, , 2014. This thalamo-striatal projection exerts direct modulation of the striatum, so that thalamic regions not only relay information from the basal ganglia to cortex, but the same regions project back to the striatum, providing direct feedback ).…”

mGluR4-containing corticostriatal terminals: synaptic interactions with direct and indirect pathway neurons in mice

“…Thus, one of the goals of this study was to assess the proportion of striatal glutamatergic terminals that co-express mGluR4 and the vesicular glutamate transporter 1 (vGluT1), a marker of cortical terminals (Fremeau et al, 2004, Lacey et al, 2005, Raju et al, 2008, Smith et al, 2014), in the mouse striatum. Knowing that the main targets of cortical glutamatergic terminals in the striatum are the two main populations of striatal output neurons (so-called direct and indirect pathway neurons), and that activation of either pathway induces opposite effects upon basal ganglia outflow and consequent motor behavior (Kravitz et al, 2010, Kravitz et al, 2012, Freeze et al, 2013), a second goal of this study was to determine if cortical mGluR4-positive terminals preferentially target a specific population of striatal projection neurons.…”