Role of the Dorsal Striatum in Cognitive Functions and Related Disorders with Cognitive Impairment.

Abstract

The dorsal striatum, recognized as a primary input nucleus of the basal ganglia, has traditionally been viewed as a crucial center for motor control. However, emerging evidence over the past five decades has sparked a paradigm shift, underscoring its vital role in a wide array of higher-order cognitive functions such as procedural learning, habit formation, working memory, executive function, and inhibitory control. This expanded understanding is grounded in the dorsal striatum's intricate architecture, which includes GABAergic Medium Spiny Neurons (MSNs) that form both the direct and indirect pathways, a diverse array of interneurons, and a compartmental organization characterized by striosomes and matrix. Furthermore, the dorsal striatum plays a pivotal role within the cortico-basal ganglia-thalamo-cortical loops and is influenced by the midbrain dopaminergic system. Dysfunction of the dorsal striatum, marked by neurotransmitter imbalances-such as dopaminergic depletion in Parkinson's Disease (PD) and cholinergic deficits in Alzheimer's Disease (AD)-along with synaptic plasticity impairments and the aggregation of pathological proteins (e.g., α-synuclein in PD and amyloid-β/tau in AD), is closely associated with cognitive decline in major neurodegenerative disorders. This review aims to provide a systematic overview of the structural and functional foundations of the dorsal striatum in cognitive regulation. It delineates the pathological mechanisms that contribute to cognitive impairments observed in PD and AD and addresses current challenges as well as future research directions. The goal is to establish a comprehensive framework that positions the dorsal striatum as a shared therapeutic target for cognitive dysfunction across various diseases, thereby offering valuable insights for the development of early diagnostic biomarkers and innovative intervention strategies.