Nicholas J. Michelson

Across cortex, a substantial component of observed neuronal activity can be explained by movement. Voluntary movements elicit cortical activity that contain elements related to both motor planning and sensory activity. However, automatic movements that do not require conscious processing, for example grooming or drinking, are to a large extent controlled by subcortical systems such as the brainstem. While the cortex may not be required to generate these automatic behaviors, it is unclear whether cortical activity represents the movements associated with them. In this work, we use a simple procedure to stimulate stereotyped grooming behaviors in the head-fixed mouse while measuring neuronal function across the dorsal cortex. We find specific cortical representations of grooming both at a mesoscale network-level and single-cell resolution. Mesoscale cortical activation was most prominent at the onset of grooming episodes, and declined to baseline levels despite continuous engagement in the behavior. Further stratification of grooming component movements revealed that more directed and unilateral grooming movements had greater cortical associated responses than more stereotyped bilateral movements. These findings help to frame the impact of forms of automatic movements on large scale cortical ensembles and suggest they engage specific and transient cellular and regional cortical ensembles.

Across cortex, a substantial component of observed neuronal activity can be explained by movement. Voluntary movements elicit cortical activity that contain elements related to both motor planning and sensory activity. However, automatic movements that do not require conscious processing, for example grooming or drinking, are to a large extent controlled by subcortical systems such as the brainstem. While the cortex may not be required to generate these automatic behaviors, it is unclear whether cortical activity represents the movements associated with them. In this work, we use a simple procedure to stimulate stereotyped grooming behaviors in the head-fixed mouse while measuring neuronal function across the dorsal cortex. We find specific cortical representations of grooming both at a mesoscale network-level and single-cell resolution. Mesoscale cortical activation was most prominent at the onset of grooming episodes, and declined to baseline levels despite continuous engagement in the behavior. Further stratification of grooming component movements revealed that more directed and unilateral grooming movements had greater cortical associated responses than more stereotyped bilateral movements. These findings help to frame the impact of forms of automatic movements on large scale cortical ensembles and suggest they engage specific and transient cellular and regional cortical ensembles.

Implantable devices to measure neurochemical or electrical activity from the brain are mainstays of neuroscience research and have become increasingly utilized as enabling components of clinical therapies. In order to increase the number of recording channels on these devices while minimizing the immune response, flexible electrodes under 10 µm in diameter have been proposed as ideal next-generation neural interfaces. However, the representation of motion artifact during neurochemical or electrophysiological recordings using ultra-small, flexible electrodes remains unexplored. In this short communication, we characterize motion artifact generated by the movement of 7 µm diameter carbon fiber electrodes during electrophysiological recordings and fast-scan cyclic voltammetry (FSCV) measurements of electroactive neurochemicals. Through in vitro and in vivo experiments, we demonstrate that artifact induced by motion can be problematic to distinguish from the characteristic signals associated with recorded action potentials or neurochemical measurements. These results underscore that new electrode materials and recording paradigms can alter the representation of common sources of artifact in vivo and therefore must be carefully characterized.

Electrical stimulation of the brain has become a mainstay of fundamental neuroscience research and an increasingly prevalent clinical therapy. Despite decades of use in basic neuroscience research and the growing prevalence of neuromodulation therapies, gaps in knowledge regarding activation or inactivation of neural elements over time have limited its ability to adequately interpret evoked downstream responses or fine-tune stimulation parameters to focus on desired responses. In this work, in vivo two-photon microscopy was used to image neuronal calcium activity in layer 2/3 neurons of somatosensory cortex (S1) in male C57BL/6J-Tg(Thy1-GCaMP6s)GP4.3Dkim/J mice during 30 s of continuous electrical stimulation at varying frequencies. We show frequency-dependent differences in spatial and temporal somatic responses during continuous stimulation. Our results elucidate conflicting results from prior studies reporting either dense spherical activation of somas biased towards those near the electrode, or sparse activation of somas at a distance via axons near the electrode. These findings indicate that the neural element specific temporal response local to the stimulating electrode changes as a function of applied charge density and frequency. These temporal responses need to be considered to properly interpret downstream circuit responses or determining mechanisms of action in basic science experiments or clinical therapeutic applications. Significance Statement: Microstimulation of small populations of neurons has the potential to ameliorate symptoms associated with several neurological disorders. However, the specific mechanisms by which microstimulation elicits therapeutic responses are unclear. This work examines the effects of continuous microstimulation on the local population of neurons surrounding the implanted electrode. Stimulation was found to elicit spatiotemporal neuronal responses in a frequency dependent manner. These findings suggest that stimulation frequency may be an important consideration for applications in research or therapy. Further research aimed at understanding these neuronal activation properties may provide insight into the mechanistic mode of action of continuous microstimulation.