Connectivity of the corticostriatal and thalamostriatal systems in normal and parkinsonian states: An update

Abstract

The striatum receives abundant glutamatergic afferents from the cortex and thalamus. These inputs play a major role in the functions of the striatal neurons in normal conditions, and are significantly altered in pathological states, such as Parkinson's disease. This review summarizes the current knowledge of the connectivity of the corticostriatal and thalamostriatal pathways, with emphasis on the most recent advances in the field. We also discuss novel findings regarding structural changes in cortico- and thalamostriatal connections that occur in these connections as a consequence of striatal loss of dopamine in parkinsonism.

Keywords: Cortex; Parkinsonism; Striatal neurons; Striatum; Thalamo.

Figure 1:. Synaptic strength and innervation of four inputs to five striatal cell types.

A: Schematic summarizing which input is most robustly exciting each cell type. Primary sensory (S1), primary motor (M1) (ipsi (M1i) or contralateral (M1c)) and prefrontal (PF) cortex projection to the different striatal projecting neurons (D1-MSN; D2-MSN), Fast-spiking interneurons (FSI), low threshold spiking interneurons (LTSI) and cholinergic interneurons (ChIN). B: schematic illustrating which cell types are most robustly excited by each input. The thickness of the arrow reflect how strong responding neurons are excited by each input (from Johansson and Silberberg 2020).

Figure 2:. PT neurons amplify excitatory inputs to striatum through ChIs.

Summary of the results: left, circuit diagram proposed for corticostriatal connectivity. IT and PT cortical neurons project to both projection neurons (SPNs) (1) and ChINs (2). While PT➔SPN (1, red) and PT➔ChI (2, red) input strength is similar, IT➔ChI (2, blue) connection is weaker than IT➔SPN (1, blue). Within the striatum, ChIs convey excitation to SPNs by recruiting long-range glutamate-releasing terminals reaching DLS through α4-containing nicotinic receptors (3). Right: Schematic of the activation of the different circuit players upon IT or PT photostimulation and its impact on the recorded SPNs. Magenta horizontal lines represent ChI spiking threshold (from Morgenstern et al. 2022).

Figure 3:. Summary of thalamic and cortical inputs to striatum.

(A) Inputs to each type of SPN and to 3 main classes of interneurons. The origins of cortical inputs are indicated for interneurons when known, according to viral tracing studies in rodents. (B) Synaptic pattern of connectivity of thalamic and cortical inputs onto SPNs. See main text for abbreviations (figured made in part with BioRender)

Figure 4:. Model of remodeling of cortico and thalamic terminals in parkinsonism.

According to studies in unilaterally treated 6-OHDA treated mice, in the parkinsonian state thalamic neurons exert a more potent activation of iSPNs than in normal animals. This increase is mediated by PF connections onto ChINs, which activate, through acetylcholine release, presynaptic nicotinic receptors on PF terminals (from Tanimura et al. 2019)