Lal, N. | Search bioRxiv

bioRxiv2023

Phosphorylation of pyruvate dehydrogenase marks the inhibition of in vivo neuronal activity

For decades, the expression of immediate early genes (IEGs) such as c-fos has been the most widely used molecular marker representing neuronal activation. However, to date, there is no equivalent surrogate available for the decrease of neuronal activity (i.e., inhibition). Here, we developed an optogenetic-based biochemical screen in which population neural activities can be controlled by light with single action potential precision, followed by unbiased phosphoproteomic profiling. We identified that the phosphorylation of pyruvate dehydrogenase (pPDH) inversely correlated with the intensity of action potential firing in primary neurons. In in vivo mouse models, monoclonal antibody-based pPDH immunostaining detected neuronal inhibition across the brain induced by a wide range of factors including general anesthesia, sensory experiences, and natural behaviors. Thus, as an in vivo marker for neuronal inhibition, pPDH can be used together with IEGs or other cell-type markers to profile and identify bi-directional neural dynamics induced by experiences or behaviors.

neuroscience↗

bioRxiv2023

Intralimb locomotor coordination in rats walking on asymmetric pegway

Complex movements such as walking or reaching are generated by a sequence of muscle actions. How these coordinated actions subserve complex movements and their recovery after disruption remains unknown. The use of high throughput recording-stimulation systems with microelectrode access to structures along the neuraxis may complement the neurological models in rodents. To this purpose, we have trained rats to perform the precise foot placement locomotor task that allows us to assess skilled locomotor movements. Animals were pretrained on the peg walkway task, which was configured to impose either symmetric or asymmetric (with overstepping) locomotor stepping at preferred stride length. Selected forelimb muscles were implanted with intramuscular differential electrodes. After a week of recovery, we collected electromyography from the implanted muscles and ground reaction forces from the array of force sensors embedded into walkway pegs. The temporal relationship between muscle bursts was measured for each intralimb set of muscles (n=13) in symmetric and asymmetric stepping. The sequence corresponded to the progression of muscle actions responsible for limb lift, flexion and transport, overground clearance, and preparation for ground contact. The stereotyped spatiotemporal sequence of muscle activity was persistent and mirroring across the asymmetric tasks. These patterns are similar to those observed in cats during locomotion with and without obstacles and reaching movements. These findings support the hypothesis that the profiles of muscle activations are qualitatively similar across quadrupeds during precise locomotor tasks. New and NoteworthyWe characterize for the first time the spatiotemporal muscle activation in rat forelimb during precise asymmetric stepping on asymmetrically placed rungs. Similar to cats, the intralimb pattern of muscle activation in rats was stereotypical. The elements of this pattern were changing in a lateralized fashion based on the direction of the imposed asymmetry. The similarity of pattern to that of cats supports the idea of similarity of neural control across cat and rat species.

neuroscience↗