Biology subjects

Michelson, N. J.

Publications and source records attributed to Michelson, N. J..

3 recordsLinked to original sources

bioRxiv2025

Widespread cortical representations of innate behaviors in the mouse

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.

neuroscience↗

bioRxiv2025

Characterization of iGABASnFR2 for in vivo mesoscale imaging of intracortical GABA dynamics

While genetically encoded sensors have advanced the study of cortical excitation, tools for large-scale imaging of inhibition remain limited. Visualizing extracellular GABA dynamics in vivo is essential for understanding how inhibitory networks shape brain activity across sensory, behavioral, and pharmacological states. To validate and apply the genetically encoded sensor iGABASnFR2 for wide-field imaging of extracellular GABA, and to characterize how cortical inhibition reorganizes across brain states, sensory modalities, and after GABA transporter blockade. We performed mesoscale imaging in head-fixed C57BL/6 mice systemically expressing iGABASnFR2. Recordings were conducted under isoflurane anesthesia, during quiet wakefulness, natural sleep (NREM and REM), and after administration of the GAT-1 inhibitor Tiagabine. We analyzed both sensory-evoked and spontaneous GABA signals using time-series, spectral, and seed-pixel correlation analyses. iGABASnFR2 demonstrated strong and modality-specific GABAergic responses to sensory stimulation, with faster and stronger activation in the contralateral cortex. Although the general spatial patterns of sensory-evoked GABA responses were consistent across anesthesia and quiet wakefulness, the amplitude, timing, and spread of these responses were significantly greater during wakefulness. During spontaneous activity, cortical GABA levels and connectivity modulated by brain state: GABA amplitude and interhemispheric synchrony were highest during quiet wakefulness but reduced during NREM sleep. Tiagabine elevated baseline GABA levels, abolished stimulus-evoked responses, and enhanced local and long-range inhibitory synchrony. iGABASnFR2 enables reliable, high-resolution imaging of cortical GABA dynamics in vivo. These results demonstrate that inhibitory signaling is dynamically structured across brain states and can be pharmacologically modulated. This tool offers new opportunities to explore the role of inhibition in health and disease at the mesoscale level.

neuroscience↗

bioRxiv2018

Calcium activation of frequency dependent temporally phasic, localized, and dense population of cortical neurons by continuous electrical stimulation

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.\n\nSignificance StatementMicrostimulation 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.

neuroscience↗