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

Cell, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

---

Cerebellar control of targeted tongue movements

The Journal of Physiology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 26, 2025

Abstract The cerebellum is critical for coordinating movements related to eating, drinking and swallowing, all of which require proper control the tongue. Cerebellar Purkinje cells can encode tongue movements, but it unclear how their simple spikes complex induce changes in shape that contribute goal‐directed movements. To study these relations, we recorded stimulated vermis hemispheres mice during spontaneous licking from a stationary or moving water spout. We found rhythmic with both spikes. Increased spike firing protrusion induces ipsiversive bending Unexpected target location trigger alter subsequent licks, adjusting trajectory. Furthermore, observed increased behavioural state at start end bouts. Using machine learning, confirmed alterations cell activity accompany licking, different often exerting heterogeneous encoding schemes. Our data highlight directional movement paramount cerebellar function modulation are complementary acquisition execution sensorimotor coordination. These results bring us closer understanding clinical implications disorders swallowing. image Key points When drinking, make directed towards source. fire rhythmically tune position source affects direction report also adjust right direction.

Язык: Английский

---

Implications of variable synaptic weights for rate and temporal coding of cerebellar outputs

eLife, Год журнала: 2024, Номер 13

Опубликована: Янв. 19, 2024

Purkinje cell (PC) synapses onto cerebellar nuclei (CbN) neurons allow signals from the cortex to influence rest of brain. PCs are inhibitory that spontaneously fire at high rates, and many PC inputs thought converge each CbN neuron suppress its firing. It has been proposed convey information using a rate code, synchrony timing or both. The on firing was primarily examined for combined effects with comparable strengths, individual not extensively studied. Here, we find single highly variable in size, dynamic clamp modeling reveal this important implications PC-CbN transmission. Individual regulate both Large strongly rates transiently eliminate several milliseconds. Remarkably, refractory period leads brief elevation prior suppression. Thus, suited concurrently codes generate precisely timed responses neurons. Either synchronous pauses promote rapid time scales nonuniform inputs, but less effectively than uniform inputs. This is secondary consequence input sizes elevating baseline by increasing variability conductance. These findings may generalize other brain regions synapse sizes.

Язык: Английский

---

Alpha6-containing GABAA receptors – Novel targets for the treatment of schizophrenia

Pharmacological Research, Год журнала: 2025, Номер unknown, С. 107613 - 107613

Опубликована: Янв. 1, 2025

Язык: Английский

---

Strategies to decipher neuron identity from extracellular recordings in the cerebellum of behaving non-human primates

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

Abstract Identification of neuron type is critical to understand computation in neural circuits through extracellular recordings awake, behaving animal subjects. Yet, modern recording probes have limited power resolve type. Here, we leverage the well-characterized architecture cerebellar circuit perform expert identification from non-human primates. Using deep-learning classifiers evaluate information contained readily accessible features for identification. Waveform, discharge statistics, anatomical layer, and functional interactions each can inform labels a sizable fraction units. Together, as inputs classifier, even better. Our tools methodologies, validated during smooth pursuit eye movements floccular complex awake monkeys, guide cerebellar-dependent tasks animals across species. They lay groundwork characterization processing cortex. Impact statement To how brain performs computations service behavior, develop methods link activity within circuits. show derived provide complementary disambiguate identity

Язык: Английский

---

A vector calculus for neural computation in the cerebellum

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 14, 2024

When a neuron modulates its firing rate during movement, we tend to assume that it is contributing control of movement. However, null space theory makes the counter-intuitive prediction neurons often generate spikes not cause behavior, but prevent effects other would have on behavior. What missing direct way test this in brain. Here, found marmoset cerebellum, spike-triggered averaging identified potent vector unique each Purkinje cell (P-cell) along which displaced eyes. Yet, P-cells were active just for saccades their vector, all saccades. Simultaneous recordings revealed two different produced superposition vectors. The result was population activity canceled if contributions perpendicular intended But why one producing be by another neuron? To answer question, recorded from mossy fiber inputs and interneurons molecular layer. We fibers provided copy motor commands as well sensory goal then transformed these so predicted when movement had reached should stopped. Because output faster dynamics than present individual neurons, cerebellum placed cells subtractive competition with such downstream spiking partially or completely eliminated because neuron.

Язык: Английский

---

Non-allometric expansion and enhanced compartmentalization of Purkinje cell dendrites in the human cerebellum

Опубликована: Янв. 30, 2025

Purkinje cell (PC) dendrites are optimized to integrate the vast cerebellar input array and drive sole cortical output. PCs classically seen as stereotypical computational units, yet mouse morphologically diverse those with multi-branched structure can receive non-canonical climbing fiber (CF) multi-innervation that confers independent compartment-specific signaling. While otherwise uncharacterized, human universally multi-branched. Do they exceed allometry achieve enhanced integrative capacities relative PCs? To answer this, we used several comparative histology techniques in adult analyze cellular morphology, parallel (PF) CF arrangement, regional PC demographics. Human substantially larger than previously described; allometric constraint by thickness largest neuron brain 6-7cm total dendritic length. Unlike mouse, ramify horizontally form a multi-compartment motif show multiple CFs. spines denser (6.9 vs 4.9 spines/μm), (∼0.36 0.29μm), include an unreported ‘spine cluster’ structure—features may be congruent PF association amplification human-specific adaptations. By extrapolation, 500,000 1 million synaptic inputs compared 30-40,000 mouse. Collectively, morphology arrangement is quantitatively qualitatively distinct from rodent. Multi-branched more prevalent posterior lateral cerebellum, co-varying functional boundaries, supporting hypothesis this morphological permits expanded multiplexing subserve task-dependent needs for association.

Язык: Английский

---

Non-allometric expansion and enhanced compartmentalization of Purkinje cell dendrites in the human cerebellum

Опубликована: Янв. 30, 2025

Purkinje cell (PC) dendrites are optimized to integrate the vast cerebellar input array and drive sole cortical output. PCs classically seen as stereotypical computational units, yet mouse morphologically diverse those with multi-branched structure can receive non-canonical climbing fiber (CF) multi-innervation that confers independent compartment-specific signaling. While otherwise uncharacterized, human universally multi-branched. Do they exceed allometry achieve enhanced integrative capacities relative PCs? To answer this, we used several comparative histology techniques in adult analyze cellular morphology, parallel (PF) CF arrangement, regional PC demographics. Human substantially larger than previously described; allometric constraint by thickness largest neuron brain 6-7cm total dendritic length. Unlike mouse, ramify horizontally form a multi-compartment motif show multiple CFs. spines denser (6.9 vs 4.9 spines/μm), (∼0.36 0.29μm), include an unreported ‘spine cluster’ structure—features may be congruent PF association amplification human-specific adaptations. By extrapolation, 500,000 1 million synaptic inputs compared 30-40,000 mouse. Collectively, morphology arrangement is quantitatively qualitatively distinct from rodent. Multi-branched more prevalent posterior lateral cerebellum, co-varying functional boundaries, supporting hypothesis this morphological permits expanded multiplexing subserve task-dependent needs for association.

Язык: Английский

---

Neural circuit mechanisms to transform cerebellar population dynamics for motor control in monkeys

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 22, 2025

Abstract We exploit identification of neuron types during extracellular recording to demonstrate how the cerebellar cortex’s well-established architecture transforms inputs into outputs. During smooth pursuit eye movements, floccular complex performs distinct input-output transformations temporal dynamics and directional response properties. The responses different interneuron localize circuit mechanisms each transformation. Mossy fibers unipolar brush cells emphasize position uniformly across cardinal axes; Purkinje molecular layer interneurons code velocity along directionally biased Golgi show unmodulated firing. Differential properties transformation last-order cells. pinpoint site granule Specific cell population allow required in area we study generalize many transformations, providing a complete framework understand computation. Impact statement dissect computations performed by cerebellum an exemplar sensory-motor behavior, taking advantage knowledge architecture, existence discrete types, newfound ability identify from recordings. Our results describe contributions major computations, needed support those create basis set enable temporally-specific motor behavior learning.

Язык: Английский

---

A Gene-Expression Based Comparison of Murine and Human Inhibitory Interneurons in the Cerebellar Cortex and Nuclei

The Cerebellum, Год журнала: 2025, Номер 24(2)

Опубликована: Фев. 28, 2025

Abstract Cerebellar information processing is critically shaped by several types of inhibitory interneurons forming various intra-cerebellar feed-forward and feed-back loops. Evidence gathered over the past decades has focused interest on a non-uniform set cortical distinct from “classical” Golgi, basket or stellate cells, summarily referred to as PLIs (for Purkinje cell layer interneurons). Similarly, cerebellar nuclear have gained increasing attention. Our understanding functions these cells still fragmentary. For humans, we lack functional data, even any dependable morphological classification for cells. Here, I used publicly available single based gene expression data compare cortex neurons humans mice. Integration revealed transcriptomic similarities between subsets suggest known characteristics may be helpful devise strategies further characterization interneurons. Comparison human murine indicate that strongly differ genes characterize in This limits their utility identify classify PLIs, leaves question open number non-Golgi resident granule layers humans.

Язык: Английский

---