Biology subjects

Cieslak, P. E.

Publications and source records attributed to Cieslak, P. E..

3 recordsLinked to original sources

bioRxiv2025

The role of dopamine-sensitive motor cortical circuits in the development and execution of skilled forelimb movements

Dopamine signalling in the motor cortex is crucial for motor skill learning. Here we resolve the spatiotemporal dopamine dynamics and the activity of local dopaminoceptive circuits during the formation and execution of motor skills. We trained head-fixed mice to perform skilled forelimb movements with a joystick to collect water rewards, while simultaneously monitoring dopamine release and calcium dynamics in the forelimb area of motor cortex. We found that dopamine release events and calcium transients were temporally linked to joystick movements and reward consumption. Dopamine dynamics and population level activity of dopamine-receptive neurons scaled with the vigor of forelimb movements and tracked the relationship between actions and their consequences. Optogenetic photoinhibition of cortical dopaminoceptive circuits reduced the number of rewarded joystick movements. Our findings show how phasic dopamine signals in the motor cortex facilitate reinforcement motor learning of skilled behavior.

neuroscience↗

bioRxiv2023

Dopamine receptor-expressing neurons are differently distributed throughout layers of the motor cortex to control dexterity

The motor cortex comprises the primary descending circuits for flexible control of voluntary movements and is critically involved in motor skill learning. Motor skill learning is impaired in patients with Parkinsons disease, but the precise mechanisms of motor control and skill learning are still not well understood. Here we have used transgenic mice, electrophysiology, in situ hybridization and neural tract-tracing methods to target genetically defined cell types expressing D1 and D2 dopamine receptors (D1+ and D2+, respectively) in the motor cortex. We observed that D1+ and D2+ neurons are organized in highly segregated, non-overlapping populations. Moreover, based on ex vivo patch-clamp recordings, we showed that D1+ and D2+ cells have distinct morphological and electrophysiological properties. Finally, we observed that chemogenetic inhibition of D2+, but not D1+ neurons, disrupts skilled forelimb reaching in adult mice. Overall, these results demonstrate that dopamine receptor-expressing cells in the motor cortex are highly segregated and play a specialized role in manual dexterity.

neuroscience↗

bioRxiv2018

Ablation of NMDA receptors in dopamine neurons disrupts attribution of incentive salience to reward-paired stimuli

Midbrain dopamine (DA) neurons play a crucial role in the formation of conditioned associations between environmental cues and appetitive events. Activation of N-methyl-D-aspartate (NMDA) receptors is a key mechanism responsible for the generation of conditioned responses of DA neurons to reward cues. Here, we tested the effects of the cell type-specific inactivation of NMDA receptors in DA neurons in adult mice on stimulus-reward learning. Animals were trained in a Pavlovian learning paradigm in which they had to learn the predictive value of two conditioned stimuli, one of which (CS+) was paired with the delivery of a water reward. Over the course of conditioning, mutant mice learned that the CS+ predicted reward availability, and they approached the reward receptacle more frequently during CS+ trials than CS- trials. However, conditioned responses to the CS+ were weaker in the mutant mice, possibly indicating that they did not attribute incentive salience to the CS+. To further assess whether the attribution of incentive salience was impaired by the mutation, animals were tested in a conditioned reinforcement test. The test revealed that mutant mice made fewer instrumental responses paired with CS+ presentation, confirming that the CS+ had a weaker incentive value. Taken together, these results indicate that reward prediction learning does occur in the absence of NMDA receptors in DA neurons, but the ability of reward-paired cues to invigorate and reinforce behavior is lost.

animal behavior and cognition↗