Biology subjects

Sanchez-Lopez, A.

Publications and source records attributed to Sanchez-Lopez, A..

3 recordsLinked to original sources

bioRxiv2024

A deep-learning strategy to identify cell types across species from high-density extracellular recordings

High-density probes allow electrophysiological recordings from many neurons simultaneously across entire brain circuits but dont reveal cell type. Here, we develop a strategy to identify cell types from extracellular recordings in awake animals, revealing the computational roles of neurons with distinct functional, molecular, and anatomical properties. We combine optogenetic activation and pharmacology using the cerebellum as a testbed to generate a curated ground-truth library of electrophysiological properties for Purkinje cells, molecular layer interneurons, Golgi cells, and mossy fibers. We train a semi-supervised deep-learning classifier that predicts cell types with greater than 95% accuracy based on waveform, discharge statistics, and layer of the recorded neuron. The classifiers predictions agree with expert classification on recordings using different probes, in different laboratories, from functionally distinct cerebellar regions, and across animal species. Our classifier extends the power of modern dynamical systems analyses by revealing the unique contributions of simultaneously-recorded cell types during behavior.

neuroscience↗

bioRxiv2023

Somatodendritic orientation determines tDCS-induced neuromodulation of Purkinje cell activity in awake mice.

Transcranial direct-current stimulation (tDCS) of the cerebellum is a promising non-invasive neuromodulatory technique being proposed for the treatment of neurological and neuropsychiatric disorders. However, there is a lack of knowledge about how externally applied currents affect neuronal spiking activity in cerebellar circuits in vivo. We investigated how Cb-tDCS affects the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex to understand the underlying mechanisms behind the polarity-dependent modulation of neuronal activity induced by tDCS. Mice (n = 9) were prepared for the chronic recording of LFPs to assess the actual electric field gradient imposed by Cb-tDCS in our experimental design. Single-neuron extracellular recording of PCs in awake (n = 24) and anesthetized (n = 27) mice was combined with juxtacellular recordings and subsequent staining of PC with neurobiotin under anesthesia (n = 8) to correlate their neuronal orientation with their response to Cb-tDCS. Finally, a high-density Neuropixels recording system was used to demonstrate the relevance of neuronal orientation during the application of Cb-tDCS in awake mice (n = 6). In this study, we observe that Cb-tDCS induces a heterogeneous polarity-dependent modulation of the firing rate of Purkinje cells (PC) and non-PC in the mouse cerebellar cortex. We demonstrate that the apparently heterogeneous effects of tDCS on PC activity can be explained by taking into account the somatodendritic orientation relative to the electric field. Our findings highlight the need to consider neuronal orientation and morphology to improve tDCS computational models, enhance stimulation protocol reliability, and optimize effects in both basic and clinical applications.

neuroscience↗

bioRxiv2020

Impact of chronic transcranial Random-Noise Stimulation (tRNS) on prefrontal cortex excitation-inhibition balance in juvenile mice.

Transcranial random noise stimulation (tRNS), a non-invasive neuromodulatory technique capable of altering cortical activity, has been proposed to improve the signal-to-noise ratio at the neuronal level and the sensitivity of the neurons following an inverted U-function. The aim of this study was to examine the effects of tRNS on vGLUT1 and GAD 65-67 and its safety in terms of pathological changes. For that, juvenile mice were randomly distributed in three different groups: "tRNS 1x" receiving tRNS at the density current used in humans (0.3 A/m2, 20 min), "tRNS 100x" receiving tRNS at two orders of magnitude higher (30.0 A/m2, 20 min) and "sham" (0.3 A/m2, 15 s). Nine tRNS sessions during five weeks were administered to the prefrontal cortex of alert animals. No detectable tissue macroscopic lesions were observed after tRNS sessions. Post-stimulation immunohistochemical analysis of GAD 65-67 and vGLUT1 immunoreactivity showed a reduced GAD 65-67 immunoreactivity levels in the region directly beneath the electrode for tRNS 1x group with no significant effects in the tRNS 100x nor sham group. The observed results points to an excitatory effect associated with a decrease in GABA levels in absence of major histopathological alterations providing a novel mechanistic explanation for tRNS effects.

neuroscience↗