The parafascicular thalamic complex and basal ganglia circuitry: further complexity to the basal ganglia model

Abstract

This work is focused on the study of neuronal circuits arising from the rodent caudal intralaminar nuclei and their presumed role on basal ganglia function. Emphasis was placed on the analysis of the architecture of thalamostriatal and thalamo-subthalamic projections in albino rats. Our major interest was to elucidate whether thalamic inputs were related to projection neurons or local circuit neurons within targeted structures (striatum and subthalamic nucleus). Projections coming from the parafascicular nucleus (PF) to the striatum displayed a patchy organization throughout the matrix compartment. These patches are composed by dense terminal axonal arborizations, often containing striatal neurons projecting to the entopeduncular nucleus (ENT) (medial globus pallidus in primates) and neurons projecting to the substantia nigra reticulata (SNR). The thalamostriatal projections under scrutiny were also seen to be in register with all the major classes of striatal interneurons (nitrergic neurons, neurons containing the calcium binding protein parvalbumin (PV) and cholinergic interneurons). Subthalamic neurons projecting to the ENT are the presumed postsynaptic target for fibers coming from the sensorimotor part (dorsolateral) of the PF. In summary, glutamatergic axons arising from the PF might exert a dual control of the striatal output, either by directly exciting striatal projection neurons or indirectly by means of a previous synaptic contact onto an striatal interneuron which in turn modulates the activity of projection neurons. Furthermore, thalamic inputs can also gain access to basal ganglia output nuclei via subthalamo-pallidal projecting neurons, neurons receiving glutamatergic thalamo-subthalamic projections. Thus, activation of either circuit has an opposite physiological effect on the basal ganglia output nucleus. Taken together, these data suggest that the PF may influence neuronal activity in the direct and indirect circuits and could be considered as an additional component of the basal ganglia motor loops.

Functional Neuroanatomy of the Basal Ganglia

“…This simplistic view, which only considered GABAergic input from the GPe and STN efferents targeting basal ganglia output nuclei, has been superseded by much experimental evidence that emerged shortly after the model was first introduced (see section, "Pathophysiology: A Summary," below). Besides the classical GABAergic projection from GPe neurons (second relay station of the indirect pathway), the STN also receives glutamatergic projections from the cerebral cortex (known as the hyperdirect pathway) (see Nambu et al 2002;Nambu 2004Nambu , 2005 and the ipsilateral thalamic caudal intralaminar nuclei Royce and Mourey 1985;Sadikot et al 1992a,b;Sidibé and Smith 1996;Marini et al 1999;Gonzalo et al 2002;Lanciego et al 2004Lanciego et al , 2009Castle et al 2005), as well as a minor projection from the contralateral caudal intralaminar nuclei (Gerfen et al 1982;Castle et al 2005). Finally, it is also worth noting that the STNalso receives a sparse dopaminergic projection from the SNc, as a part of the so-called nigro-extrastriatal projection system (for review, see Rommelfanger and Wichmann 2010).…”

“…Furthermore, cortical inputs arising from the primary motor cortex, the supplementary motor area, premotor cortices, frontal eye field area, and supplementary eye field area are conveyed through the cortico-subthalamic hyperdirect pathway, somatotopically organized at the level of the STN (Nambu et al 1996(Nambu et al , 2002. The direct projection arising from the caudal intralaminar nuclei is another important source of glutamatergic activation, described in rodents, cats, and primates Royce and Mourey 1985;Sadikot et al 1992;Sidibé and Smith 1996;Marini et al 1999;Gonzalo et al 2002;Lanciego et al 2004Lanciego et al , 2009Castle et al 2005). Thalamo-subthalamic projections are topographically organized (Sadikot et al 1992;Lanciego et al 2004), reaching STN efferent neurons innervating the GPe and SNr/GPi (Castle et al 2005).…”

“…Until recently, the thalamostriatal pathway had been largely neglected in most modern models summarizing basal ganglia circuits. Virtually all types of striatal neurons are contacted by thalamostriatal afferents, which include projection neurons (Dubé et al 1988;Sidibé and Smith 1999;Gonzalo et al 2002;Bacci et al 2004;Lanciego et al 2004;Smith et al 2004;Castle et al 2005) and striatal interneurons (Meredith and Wouterlood 1990;Bennet and Bolam 1993;Rudkin and Sadikot 1999;Sidibé and Smith 1999;Thomas et al 2000). It has been generally considered that thalamostriatal axons preferentially contact the dendritic shafts of striatal MSNs (Sadikot et al 1990;Smith and Bolam 1990;Sidibé and Smith 1996;Smith et al 2004), whereas corticostriatal afferents mainly synapse with dendritic spines.…”

Glutamic Acid Decarboxylase 67 mRNA Regulation in Two Globus Pallidus Neuron Populations by Dopamine and the Subthalamic Nucleus

“…Although the STN provides the greatest excitatory input to the GP, other areas may contribute to pallidal gene expression. For example, the parafascicular nucleus projects directly to the GP (Kincaid et al, 1991;Deschenes et al, 1996;Orieux et al, 2000;Gonzalo et al, 2002) and may importantly affect pallidal neuronal activity independently of STN inputs (Mouroux et al, 1997). Thus, parafascicular inputs to the GP may account for the remaining elevation in GAD 67 mRNA expression levels in 6-OHDA-(or eticlopride)-treated, STN-lesioned animals.…”

Lesion of the centromedian thalamic nucleus in MPTP‐treated monkeys

“…The centromedian-parafascicular thalamic complex (CM-Pf) is one major source of glutamatergic innervation of several basal ganglia nuclei, including the striatum, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] the subthalamic nucleus (STN), 4,7,[12][13][14][15][16][17][18][19][20][21] the globus pallidus, and the substantia nigra. 15,21,22 Projections arising from the caudal intralaminar nuclei are excitatory and use glutamate as neurotransmitter.…”