Pontine nuclei (PN) neurons mediate the communication between the cerebral cortex andthe cerebellum to refine skilled motor functions. Prior studies showed that PN neurons fall into two subtypes based on their anatomic location and region-specific connectivity, but the extent of their heterogeneity and its molecular drivers remain unknown.
Atoh1
encodes a transcription factor that is expressed in the PN precursors. We previously showed that partial loss of
Atoh1
function in mice results in delayed PN development and impaired motor learning. In this study, we performed single-cell RNA sequencing to elucidate the cell state–specific functions of
Atoh1
during PN development and found that
Atoh1
regulates cell cycle exit, differentiation, migration, and survival of PN neurons. Our data revealed six previously not known PN subtypes that are molecularly and spatially distinct. We found that the PN subtypes exhibit differential vulnerability to partial loss of
Atoh1
function, providing insights into the prominence of PN phenotypes in patients with
ATOH1
missense mutations.
Electroencephalography (EEG) is an indispensable clinical and research tool used to diagnose neurological disease (Davies & Gavin, 2007;Noachtar & Rémi, 2009;Tierney et al., 2012) and discover brain circuit mechanisms that support sensory, mnemonic and cognitive processing (Nuñez & Buño, 2021;Woodman, 2010). Mechanistically, EEGs are non-stationary time-series that capture alterations in the brain's electromagnetic field arising from synchronous synaptic potential changes across neuronal populations. Linear digital signal processing (DSP) tools are routinely used in EEGs to reduce noise, resample the data, remove artifacts, expose the data's spatio-temporal frequency content, and much more. Openseize is a DSP package written in pure Python that scales to very large EEG datasets, employs an extensible object-oriented architecture, and provides a familiar Scipy-like API (Virtanen et al., 2020).
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