Automated system for training and assessing reaching and grasping behaviors in rodents.

BACKGROUND: Reaching, grasping, and pulling behaviors are studied across species to investigate motor control and problem solving. String pulling is a distinct reaching and grasping behavior that is rapidly learned, requires bimanual coordination, is ethologically grounded, and has been applied across species and disease conditions. NEW METHOD: Here we describe the PANDA system (Pulling And Neural Data Analysis), a hardware and software system that integrates a continuous string loop connected to a rotary encoder, feeder, microcontroller, high-speed camera, and analysis software for the assessment and training of reaching, grasping, and pulling behaviors and synchronization with neural data. RESULTS: We demonstrate this system in rats implanted with electrodes in motor cortex and hippocampus and show how it can be used to assess relationships between reaching, pulling, and grasping movements and single-unit and local-field activity. Furthermore, we found that automating the shaping procedure significantly improved performance over manual training, with rats pulling > 100 m during a 15-minute session. COMPARISON WITH EXISTING METHODS: String-pulling is typically shaped by tying food reward to the string and visually scoring behavior. The system described here automates training, streamlines video assessment with deep learning, and automatically segments reaching movements into distinct reach/pull phases. No system, to our knowledge, exists for the automated shaping and assessment of this behavior. CONCLUSIONS: This system will be of general use to researchers investigating motor control, motivation, sensorimotor integration, and motor disorders such as Parkinson's disease and stroke.

Automated system for training and assessing string-pulling behaviors in rodents.

String-pulling tasks have been used for centuries to study coordinated bimanual motor behavior and problem solving. String pulling is rapidly learned, ethologically grounded, and has been applied to many species and disease conditions. Typically, training of string-pulling behaviors is achieved through manual shaping and baiting. Furthermore, behavioral assessment of reaching, grasping, and pulling is often performed through labor intensive manual video scoring. No system, to our knowledge, currently exists for the automated shaping and assessment of string-pulling behaviors. Here we describe the PANDA system (Pulling And Neural Data Analysis), an inexpensive hardware and software system that utilizes a continuous string loop connected to a rotary encoder, feeder, microcontroller, high-speed camera, and analysis software for assessment and training of string-pulling behaviors and synchronization with neural recording data. We demonstrate this system in unimplanted rats and rats implanted with electrodes in motor cortex and hippocampus and show how the PANDA system can be used to assess relationships between paw movements and single-unit and local-field activity. We also found that automating the shaping procedure significantly improved overall performance, with rats regularly pulling >100 meters during a 15-minute session. In conclusion, the PANDA system will be of general use to researchers investigating motor control, motivation, and motor disorders such as Parkinson's disease, Huntington's disease, and stroke. It will also support the investigation of neural mechanisms involved in sensorimotor integration.

Antagonism of kappa opioid receptors accelerates the development of L-DOPA-induced dyskinesia in a preclinical model of moderate dopamine depletion.

Levels of the opioid peptide dynorphin, an endogenous ligand selective for kappa-opioid receptors (KORs), its mRNA and pro-peptide precursors are differentially dysregulated in Parkinson's disease (PD) and following the development of l-DOPA-induced dyskinesia (LID). It remains unclear whether these alterations contribute to the pathophysiological mechanisms underlying PD motor impairment and the subsequent development of LID, or whether they are part of compensatory mechanisms. We sought to investigate nor-BNI, a KOR antagonist, 1) in the dopamine (DA)-depleted PD state, 2) during the development phase of LID, and 3) via measuring of tonic levels of striatal DA. While nor-BNI (3 mg/kg; s.c.) did not lead to functional restoration in the DA-depleted state, it affected the dose-dependent development of abnormal voluntary movements (AIMs) in response to escalating doses of l-DOPA in a rat PD model with a moderate striatal 6-hydroxdopamine (6-OHDA) lesion. We tested five escalating doses of l-DOPA (6, 12, 24, 48, 72 mg/kg; i.p.), and nor-BNI significantly increased the development of AIMs at the 12 and 24 mg/kg l-DOPA doses. However, after reaching the 72 mg/kg l-DOPA, AIMs were not significantly different between control and nor-BNI groups. In summary, while blocking KORs significantly increased the rate of development of LID induced by chronic, escalating doses of l-DOPA in a moderate-lesioned rat PD model, it did not contribute further once the overall severity of LID was established. While we observed an increase of tonic DA levels in the moderately lesioned dorsolateral striatum, there was no tonic DA change following administration of nor-BNI.

Antagonism of kappa opioid receptors accelerates the development of L-DOPA-induced dyskinesia in a preclinical model of moderate dopamine depletion.

Levels of the opioid peptide dynorphin, an endogenous ligand selective for kappa-opioid receptors (KORs), its mRNA and pro-peptide precursors are differentially dysregulated in Parkinson disease (PD) and following the development of L-DOPA-induced dyskinesia (LID). It remains unclear, whether these alterations contribute to the pathophysiological mechanisms underlying PD motor impairment and the subsequent development of LID, or whether they are part of compensatory mechanisms. We sought to investigate nor-BNI, a KOR antagonist, 1) in the dopamine (DA)-depleted PD state, 2) during the development phase of LID, and 3) with measuring tonic levels of striatal DA. Nor-BNI (3 mg/kg; s.c.) did not lead to functional restoration in the DA-depleted state, but a change in the dose-dependent development of abnormal voluntary movements (AIMs) in response to escalating doses of L-DOPA in a rat PD model with a moderate striatal 6-hydroxydopamine (6-OHDA) lesion. We tested five escalating doses of L-DOPA (6, 12, 24, 48, 72 mg/kg; i.p.), and nor-BNI significantly increased the development of AIMs at the 12 and 24 mg/kg L-DOPA doses. However, after dosing with 72 mg/kg L-DOPA, AIMs were not significantly different between control and nor-BNI groups. In summary, while blocking KORs significantly increased the rate of development of LID induced by chronic, escalating doses of L-DOPA in a moderate-lesioned rat PD model, it did not contribute further once the overall severity of LID was established. While we saw an increase of tonic DA levels in the moderately lesioned dorsolateral striatum, there was no tonic DA change following administration of nor-BNI.