Griffith, T. | Search bioRxiv

bioRxiv2023

SanPy: A whole-cell electrophysiology analysis pipeline.

The analysis of action potentials and other membrane voltage fluctuations provide a powerful approach for interrogating the function of excitable cells. Yet, a major bottleneck in the interpretation of this critical data is the lack of intuitive, agreed upon software tools for its analysis. Here, we present SanPy, a Python-based open-source and freely available software pipeline for the analysis and exploration of whole-cell current-clamp recordings. SanPy provides a robust computational engine with an application programming interface. Using this, we have developed a cross-platform graphical user interface that does not require programming. SanPy is designed to extract common parameters from action potentials including threshold time and voltage, peak, half-width, and interval statistics. In addition, several cardiac parameters are measured including the early diastolic duration and rate. SanPy is built to be fully extensible by providing a plugin architecture for the addition of new file loaders, analysis, and visualizations. A key feature of SanPy is its focus on quality control and data exploration. In the desktop interface, all plots of the data and analysis are linked allowing simultaneous data visualization from different dimensions with the goal of obtaining ground truth analysis. We provide documentation for all aspects of SanPy including several use cases and examples. To test SanPy, we have performed analysis on current-clamp recordings from heart and brain cells. Taken together, SanPy is a powerful tool for whole-cell current-clamp analysis and lays the foundation for future extension by the scientific community. News and NoteworthyWhole-cell current-clamp recording is a critical technique to understand detailed biophysical mechanisms at the cellular and network levels. Yet, the analysis of this data is by no means standardized. Here, we present SanPy, a Python based open-source software pipeline for the exploration and analysis of current-clamp recordings. SanPy provides a powerful computational engine with an application programming interface. Finally, SanPy provides a cross-platform point-and-click graphical user interface that does not require programming.

neuroscience↗

bioRxiv2022

Nav1.1 in mammalian sensory neurons is required for normal motor behaviors

AO_SCPLOWBSTRACTC_SCPLOWThe voltage-gated sodium channel (NaV), NaV1.1, is well-studied in the central nervous system; conversely, its contribution to peripheral sensory neuron function is more enigmatic. Here, we identify a new role for NaV1.1 in mammalian proprioception. RNAscope analysis and in vitro patch clamp recordings in genetically identified mouse proprioceptors show ubiquitously channel expression and significant contributions to intrinsic excitability. Notably, genetic deletion of NaV1.1 in sensory neurons caused profound and visible motor coordination deficits in conditional knockout mice of both sexes, similar to conditional Piezo2-knockout animals, suggesting this channel is a major contributor to sensory proprioceptive transmission. Ex vivo muscle afferent recordings conditional knockout mice found that loss of NaV1.1 leads to inconsistent and unreliable proprioceptor firing characterized by action potential failures during static muscle stretch; conversely, afferent responses to dynamic vibrations were unaffected. This suggests that while a combination of Piezo2 and other NaV isoforms are sufficient to elicit activity in response to transient stimuli, NaV1.1 is required for transmission of receptor potentials generated during sustained muscle stretch. Impressively, recordings from afferents of heterozygous conditional knockout animals were similarly impaired, and heterozygous conditional knockout mice also exhibited motor behavioral deficits. Thus, NaV1.1 haploinsufficiency in sensory neurons impairs both proprioceptor function and motor behaviors. Importantly, human patients harboring NaV1.1 loss-of-function mutations often present with motor delays and ataxia; therefore, our data suggest sensory neuron dysfunction contributes to the clinical manifestations of neurological disorders in which NaV1.1 function is compromised. Collectively, we present the first evidence that NaV1.1 is essential for mammalian proprioceptive signaling and behaviors.

neuroscience↗