The effect of surgery and intracerebral injections on motor skill learning in rats: results from a database analysis.

Male Long-Evans rats are often used to investigate neural mechanisms of learning in the motor system. Successful acquisition of a skilled motor task is influenced by various variables such as animal supplier and batch membership. In this retrospective analysis of our laboratory database, we investigate how head and brain surgery as well as intracerebral injections that were performed to address particular scientific questions affect motor learning. Overall, invasive interventions (n=90) slow the acquisition of a skilled-reaching task when compared to naïve animals (n=184; P=0.01). With respect to subgroups, this detrimental effect widely differs between particular procedures: whereas epidural implantations of thin-film electrode arrays and punctual injection through pre-implanted cannulas into primary motor cortex (M1) do not interfere with learning, skill acquisition is slowed after chronic infusion using osmotic minipumps into M1 and skill acquisition is lastingly impaired after bilateral cannula implantation within the dorsal striatum. In line with previous reports, breeder-specific differences could be observed in the analysis of the overall population. In summary, interventions may impair learning-behavior in an unpredictable fashion. Thus, a comparison of behavioral data to a naïve population is recommended to be aware of these drawbacks.

Sub-processes of motor learning revealed by a robotic manipulandum for rodents.

Rodent models are widely used to investigate neural changes in response to motor learning. Usually, the behavioral readout of motor learning tasks used for this purpose is restricted to a binary measure of performance (i.e. "successful" movement vs. "failure"). Thus, the assignability of research in rodents to concepts gained in human research - implying diverse internal models that constitute motor learning - is still limited. To solve this problem, we recently introduced a three-degree-of-freedom robotic platform designed for rats (the ETH-Pattus) that combines an accurate behavioral readout (in the form of kinematics) with the possibility to invasively assess learning related changes within the brain (e.g. by performing immunohistochemistry or electrophysiology in acute slice preparations). Here, we validate this platform as a tool to study motor learning by establishing two forelimb-reaching paradigms that differ in degree of skill. Both conditions can be precisely differentiated in terms of their temporal pattern and performance levels. Based on behavioral data, we hypothesize the presence of several sub-processes contributing to motor learning. These share close similarities with concepts gained in humans or primates.