Excitation, but not inhibition, of the fastigial nucleus provides powerful control over temporal lobe seizures

The Journal of Physiology, Journal Year: 2019, Volume and Issue: 598(1), P. 171 - 187

Published: Nov. 4, 2019

On-demand optogenetic inhibition of glutamatergic neurons in the fastigial nucleus cerebellum does not alter hippocampal seizures a mouse model temporal lobe epilepsy. In contrast, on-demand excitation successfully inhibits seizures. With this approach, even single 50 ms pulse light is able to significantly inhibit either ipsilateral or contralateral seizure focus Selective nuclear provides greater than broadly exciting without cell-type specificity.Temporal epilepsy most common form adults, but current treatment options provide limited efficacy, leaving as many one-third patients with uncontrolled Recently, attention has shifted towards more closed-loop therapies for control, and modulation cerebellar cortex was shown be highly effective at attenuating Intriguingly, both cortical output neurons, Purkinje cells, attenuated The mechanisms by which impacts seizures, however, are unknown. present study, we targeted immediate downstream projection vermal cells - order determine whether increases and/or decreases can underlie cessation. Though cell input inhibitory, direct had no effect on duration. Conversely, robustly Seizure cessation achieved multiple stimulation frequencies, regardless laterality relative focus, pulses. when selectively targeting an approach that lacked specificity used. Together, these results suggest stimulating excitatory may promising therapeutic intervention

Language: Английский

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Conversion of Graded Presynaptic Climbing Fiber Activity into Graded Postsynaptic Ca2+ Signals by Purkinje Cell Dendrites

Neuron, Journal Year: 2019, Volume and Issue: 102(4), P. 762 - 769.e4

Published: March 27, 2019

Language: Английский

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Purkinje Cell Activity Determines the Timing of Sensory-Evoked Motor Initiation

Cell Reports, Journal Year: 2020, Volume and Issue: 33(12), P. 108537 - 108537

Published: Dec. 1, 2020

Cerebellar neurons can signal sensory and motor events, but their role in active sensorimotor processing remains unclear. We record manipulate Purkinje cell activity during a task that requires mice to rapidly discriminate between multisensory unisensory stimuli before initiation. Neuropixels recordings show both initiation are represented by short-latency simple spikes. Optogenetic manipulation of spikes abolishes or delays rate-dependent manner, indicating its timing. Two-photon calcium imaging reveals task-related coherence complex organized into conserved alternating parasagittal stripes. The sensory-evoked increases with learning correlates enhanced temporal precision These results suggest govern sensory-driven initiation: modulate latency, refine precision, providing specific cellular substrates for cerebellar control.

Language: Английский

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The Cellular Electrophysiological Properties Underlying Multiplexed Coding in Purkinje Cells

Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 41(9), P. 1850 - 1863

Published: Jan. 15, 2021

Neuronal firing patterns are crucial to underpin circuit level behaviors. In cerebellar Purkinje cells (PCs), both spike rates and pauses used for behavioral coding, but the cellular mechanisms causing code transitions remain unknown. We use a well-validated PC model explore coding strategy that individual PCs process parallel fiber (PF) inputs. find increasing input intensity shifts from linear rate-coders burst-pause timing-coders by triggering localized dendritic spikes. validate properties with experimental data, elucidate spiking mechanisms, predict thresholds without inhibition. Both computations branches as computational units, which challenges traditional view of point neurons. Dendritic can be regulated voltage state, compartmentalized channel modulation, between-branch interaction synaptic inhibition expand dynamic range computation or computation. addition, co-activated PF inputs between modify somatic maximum pause durations make them carry analog signals. Our results provide new insights into strategies neurons their capacity information processing. SIGNIFICANCE STATEMENT Understanding how is fundamental question in neuroscience. (PCs) were traditionally regarded modeling unveil electrophysiological underlying multiplexed observed during demonstrate triggers spikes, shifting timing-coders. work at branches. suggests have ability implement branch-specific level, thereby learning.

Language: Английский

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Input and output organization of the mesodiencephalic junction for cerebro‐cerebellar communication

Journal of Neuroscience Research, Journal Year: 2021, Volume and Issue: 100(2), P. 620 - 637

Published: Dec. 1, 2021

Abstract Most studies investigating the impact of cerebral cortex (CC) onto cerebellum highlight role pons, which provides mossy fibers to cerebellum. However, cerebro‐cerebellar communication may also be mediated by nuclei mesodiencephalic junction (MDJ) that project inferior olive (IO), in turn climbing molecular layer. Here, we uncover precise topographic relations inputs and outputs MDJ using multiple, classical, transneuronal tracing methods as well analyses mesoscale cortical injections from Allen Mouse Brain. We show caudal parts CC predominantly principal via rostral medial accessory MDJ. Moreover, triple viral technology, cerebellar directly innervate neurons receive input IO. By unraveling these prominent, mono‐ disynaptic projections through MDJ, this work establishes is not only pontine fiber system, but system.

Language: Английский

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