Biology subjects

Oostland, M.

Publications and source records attributed to Oostland, M..

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↗

bioRxiv2021

Enhanced learning and sensory salience in a cerebellar mouse autism model

Perturbation to the cerebellum can lead to deficits in motor function, cognition, and behavioral flexibility. Here we report that a cerebellum-specific transgenic mouse autism model with disrupted Purkinje cell function shows unexpectedly accelerated learning on a sensory evidence-accumulation task, as well as enhanced sensory reactivity to touch and auditory cues. Computational latent-state analysis of behavior revealed that accelerated learning was associated with enhanced focus on current over past trials. In on-task states, a subset of Purkinje cells in crus I produced more complex spikes to sensory stimuli. Learning was accelerated by providing cue-locked optogenetic stimulation of Purkinje cells, but unaffected by continuous optogenetic interference with Purkinje cell activity. Complex spikes fired in response to both correct and incorrect choices, but less so when mice were on-task. Both transgenic mice and mice receiving cue-locked optogenetic stimulation showed prolonged sensory responses in Purkinje-cell complex spikes and anterior cingulate cortex. We suggest that cerebellar activity may shape evidence-accumulation learning by enhancing task focus and neocortical processing of current experience. HighlightsO_LIFaster learning and enhanced sensory salience with cerebellar manipulations in mice C_LIO_LIAccelerated learning arises from prolonged occupancy in an on-task behavioral state C_LIO_LICerebellar manipulations can influence neocortex via altered complex spike activity C_LIO_LICerebellum findings consistent with a weak global coherence account of autism C_LI eTOC blurbIn a cerebellum-based mouse autism model, perturbed function leads to faster learning of a working-memory task, mediated by higher focus on current trials. The effects are emulated by optogenetic perturbation of Purkinje cells, and both perturbations drive enhanced neocortical activity. Results are consistent with a weak coherence model for autism.

neuroscience↗

bioRxiv2018

A cerebellar role in evidence-guided decision-making

To make successful evidence-based decisions, the brain must rapidly and accurately transform sensory inputs into specific goal-directed behaviors. Most experimental work on this subject has focused on forebrain mechanisms. Here we show that during perceptual decision-making over a period of seconds, decision-, sensory-, and error-related information converge on the lateral posterior cerebellum in crus I, a structure that communicates bidirectionally with numerous forebrain regions. We trained mice on a novel evidence-accumulation task and demonstrated that cerebellar inactivation reduces behavioral accuracy without impairing motor parameters of action. Using two-photon calcium imaging, we found that Purkinje cell somatic activity encoded choice- and evidence-related variables. Decision errors were represented by dendritic calcium spikes, which are known to drive plasticity. We propose that cerebellar circuitry may contribute to the set of distributed computations in the brain that support accurate perceptual decision-making.

neuroscience↗