Unilateral damage to the entopeduncular nucleus causes dysfunction in skilled forelimb movement and hinders recovery in rats

The entopeduncular nucleus (EPN) is an output nucleus of the basal ganglia and is suggested to play a critical role in motor control. This study aimed to clarify the impact of EPN damage on skilled motor function and its recovery. Unilateral EPN damage or intracerebral hemorrhage (ICH) was induced by stereotactic injection of kainic acid (KA) into the EPN or collagenase type Ⅳ into the internal capsule, respectively. Skilled motor function was assessed by the number of trials and success rates in a single-pellet reaching task from baseline to day 28. EPN damage was quantified by immunohistochemistry for NeuN or hematoxylin–eosin staining. KA-induced EPN damage reduced the number of trials by 100% in most rats (n = 5/8) on day 2, resulting in a significantly lower success rate compared to controls ( P < 0.05). Trial reduction was transient in two rats but persisted through day 28 in three rats. Notably, success rates on day 28 positively correlated with the number of remaining NeuN-positive cells ( P < 0.05). In the ICH model, most rats (n = 10/11) reduced trials on day 2, and half (n = 5/11) remained impaired on day 28. The success rates on day 28 were positively correlated with remaining EPN volume ( P < 0.01), but not with total lesion volume. These findings demonstrated that unilateral EPN damage reduces voluntary reaching trials and impairs skilled motor function, indicating that EPN integrity is crucial for skilled motor control and may represent a critical predictor of motor prognosis after damage.