Complex spike synchrony dependent modulation of rat deep cerebellar nuclear activity

The rules governing cerebellar output are not fully understood, but must involve Purkinje cell (PC) activity, as PCs are the major input to deep cerebellar nuclear (DCN) cells (which form the majority of cerebellar output). Here, the influence of PC complex spikes (CSs) was investigated by simultaneously recording DCN activity with CSs from PC arrays in anesthetized rats. Crosscorrelograms were used to identify PCs that were presynaptic to recorded DCN cells (presynaptic PCs). Such PCs were located within rostrocaudal cortical strips and displayed synchronous CS activity. CS-associated modulation of DCN activity included a short-latency post-CS inhibition and long-latency excitations before and after the CS. The amplitudes of the post-CS responses correlated with the level of synchronization among presynaptic PCs. A temporal precision of ≤10 ms was generally required for CSs to be maximally effective. The results suggest that CS synchrony is a key control parameter of cerebellar output.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

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Developmental Changes in Evoked Purkinje Cell Complex Spike Responses

Journal of Neurophysiology ◽

10.1152/jn.00481.2003 ◽

2003 ◽

Vol 90 (4) ◽

pp. 2349-2357 ◽

Cited By ~ 10

Author(s):

Daniel A. Nicholson ◽

John H. Freeman

Keyword(s):

Motor Learning ◽

Purkinje Cell ◽

Inferior Olive ◽

Cell Complex ◽

Climbing Fibers ◽

Somatosensory Stimulation ◽

Complex Spike ◽

Long Latency ◽

Inhibitory Feedback ◽

Complex Spikes

The development of synaptic interconnections between the cerebellum and inferior olive, the sole source of climbing fibers, could contribute to the ontogeny of certain forms of motor learning (e.g., eyeblink conditioning). Purkinje cell complex spikes are produced exclusively by climbing fibers and exhibit short- and long-latency activity in response to somatosensory stimulation. Previous studies have demonstrated that evoked short- and long-latency complex spikes generally occur on separate trials and that this response segregation is regulated by inhibitory feedback to the inferior olive. The present experiment tested the hypothesis that complex spikes evoked by periorbital stimulation are regulated by inhibitory feedback from the cerebellum and that this feedback develops between postnatal days (PND) 17 and 24. Recordings from individual Purkinje cell complex spikes in urethan-anesthetized rats indicated that the segregation of short- and long-latency evoked complex spike activity emerges between PND17 and PND24. In addition, infusion of picrotoxin, a GABAA-receptor antagonist, into the inferior olive abolished the response pattern segregation in PND24 rats, producing evoked complex spike response patterns similar to those characteristic of younger rats. These data support the view that cerebellar feedback to the inferior olive, which is exclusively inhibitory, undergoes substantial changes in the same developmental time window in which certain forms of motor learning emerge.

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Faculty Opinions recommendation of Complex spike synchrony dependent modulation of rat deep cerebellar nuclear activity.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734831190.793556211 ◽

2019 ◽

Author(s):

Reza Shadmehr

Keyword(s):

Spike Synchrony ◽

Nuclear Activity ◽

Complex Spike

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Functionally distinct Purkinje cell types show temporal precision in encoding locomotion

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2005633117 ◽

2020 ◽

Vol 117 (29) ◽

pp. 17330-17337

Author(s):

Weipang Chang ◽

Andrea Pedroni ◽

Victoria Hohendorf ◽

Stefania Giacomello ◽

Masahiko Hibi ◽

...

Keyword(s):

Purkinje Cell ◽

Purkinje Cells ◽

Central Pattern Generators ◽

Cell Types ◽

Neuronal Population ◽

Adult Zebrafish ◽

Temporal Precision ◽

Distinct Cell ◽

Pattern Generators ◽

Cell Networks

Purkinje cells, the principal neurons of cerebellar computations, are believed to comprise a uniform neuronal population of cells, each with similar functional properties. Here, we show an undiscovered heterogeneity of adult zebrafish Purkinje cells, revealing the existence of anatomically and functionally distinct cell types. Dual patch-clamp recordings showed that the cerebellar circuit contains all Purkinje cell types that cross-communicate extensively using chemical and electrical synapses. Further activation of spinal central pattern generators (CPGs) revealed unique phase-locked activity from each Purkinje cell type during the locomotor cycle. Thus, we show intricately organized Purkinje cell networks in the adult zebrafish cerebellum that encode the locomotion rhythm differentially, and we suggest that these organizational properties may also apply to other cerebellar functions.

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Purkinje-Cell-Restricted Restoration of Kv3.3 Function Restores Complex Spikes and Rescues Motor Coordination in Kcnc3 Mutants

Journal of Neuroscience ◽

10.1523/jneurosci.5486-07.2008 ◽

2008 ◽

Vol 28 (18) ◽

pp. 4640-4648 ◽

Cited By ~ 51

Author(s):

E. C. Hurlock ◽

A. McMahon ◽

R. H. Joho

Keyword(s):

Purkinje Cell ◽

Motor Coordination ◽

Complex Spikes

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Brain oscillator(s) underlying rhythmic cerebral and buccal motor output in the mollusc, Pleurobranchaea californica

Journal of Experimental Biology ◽

10.1242/jeb.110.1.1 ◽

1984 ◽

Vol 110 (1) ◽

pp. 1-15

Author(s):

W. J. Davis ◽

M. P. Kovac ◽

R. P. Croll ◽

E. M. Matera

Keyword(s):

Neural Control ◽

Brain Activity ◽

Neural Oscillator ◽

Neural Oscillation ◽

Buccal Ganglion ◽

Pleurobranchaea Californica ◽

Long Latency ◽

Before And After ◽

The Central Nervous System ◽

The Brain

Tonic (d.c.) intracellular depolarization of the previously identified phasic paracerebral feeding command interneurones (PCps) in the brain of the carnivorous gastropod Pleurobranchaea causes oscillatory neural activity in the brain, both before and after transecting the cerebrobuccal connectives. Therefore, cycle-by-cycle ascending input from the buccal ganglion is not essential to cyclic brain activity. Instead the brain contains an independent neural oscillator(s), in addition to the oscillator(s) demonstrated previously in the buccal ganglion (Davis et al. 1973). Transection of the cerebrobuccal connectives immediately reduces the previously demonstrated (Kovac, Davis, Matera & Croll, 1983) long-latency polysynaptic excitation of the PCps by the polysynaptic excitors (PSEs) of the PCps. Therefore polysynaptic excitation of the PCps by the PSEs is mediated by an ascending neurone(s) from the buccal ganglion. The capacity of feeding command interneurones to induce neural oscillation in the isolated brain declines to near zero within 1 h after transection of the cerebrobuccal connectives, suggesting that this capacity is normally maintained by ascending information from the buccal ganglion. The results show that this motor system conforms to a widely applicable general model of the neural control of rhythmic behaviour, by which independent neural oscillators distributed widely in the central nervous system are coupled together to produce coordinated movement.

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High-molecular-weight polymers from dietary fiber drive aggregation of particulates in the murine small intestine

eLife ◽

10.7554/elife.40387 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 4

Author(s):

Asher Preska Steinberg ◽

Sujit S Datta ◽

Thomas Naragon ◽

Justin C Rolando ◽

Said R Bogatyrev ◽

...

Keyword(s):

Molecular Weight ◽

Small Intestine ◽

Dietary Fiber ◽

High Molecular Weight ◽

Ex Vivo ◽

Editorial Note ◽

Editorial Process ◽

Dietary Fibers ◽

Specific Chemical ◽

Molecular Weights

The lumen of the small intestine (SI) is filled with particulates: microbes, therapeutic particles, and food granules. The structure of this particulate suspension could impact uptake of drugs and nutrients and the function of microorganisms; however, little is understood about how this suspension is re-structured as it transits the gut. Here, we demonstrate that particles spontaneously aggregate in SI luminal fluid ex vivo. We find that mucins and immunoglobulins are not required for aggregation. Instead, aggregation can be controlled using polymers from dietary fiber in a manner that is qualitatively consistent with polymer-induced depletion interactions, which do not require specific chemical interactions. Furthermore, we find that aggregation is tunable; by feeding mice dietary fibers of different molecular weights, we can control aggregation in SI luminal fluid. This work suggests that the molecular weight and concentration of dietary polymers play an underappreciated role in shaping the physicochemical environment of the gut.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

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Plasmodium Niemann-Pick type C1-related protein is a druggable target required for parasite membrane homeostasis

eLife ◽

10.7554/elife.40529 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 13

Author(s):

Eva S Istvan ◽

Sudipta Das ◽

Suyash Bhatnagar ◽

Josh R Beck ◽

Edward Owen ◽

...

Keyword(s):

Electron Microscopy ◽

Plasmodium Falciparum ◽

Plasma Membrane ◽

Drug Target ◽

Editorial Note ◽

Editorial Process ◽

Related Protein ◽

Immuno Electron Microscopy ◽

Increased Sensitivity ◽

Niemann Pick

Plasmodium parasites possess a protein with homology to Niemann-Pick Type C1 proteins (Niemann-Pick Type C1-Related protein, NCR1). We isolated parasites with resistance-conferring mutations in Plasmodium falciparum NCR1 (PfNCR1) during selections with three diverse small-molecule antimalarial compounds and show that the mutations are causative for compound resistance. PfNCR1 protein knockdown results in severely attenuated growth and confers hypersensitivity to the compounds. Compound treatment or protein knockdown leads to increased sensitivity of the parasite plasma membrane (PPM) to the amphipathic glycoside saponin and engenders digestive vacuoles (DVs) that are small and malformed. Immuno-electron microscopy and split-GFP experiments localize PfNCR1 to the PPM. Our experiments show that PfNCR1 activity is critically important for the composition of the PPM and is required for DV biogenesis, suggesting PfNCR1 as a novel antimalarial drug target.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

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Hedonic processing in humans is mediated by an opioidergic mechanism in a mesocorticolimbic system

eLife ◽

10.7554/elife.39648 ◽

2018 ◽

Vol 7 ◽

Cited By ~ 14

Author(s):

Christian Buchel ◽

Stephan Miedl ◽

Christian Sprenger

Keyword(s):

Opioid Receptors ◽

Orbitofrontal Cortex ◽

Ventral Striatum ◽

Editorial Note ◽

Incentive Salience ◽

Editorial Process ◽

Opioidergic System ◽

Pharmacological Challenge ◽

Reward Delivery ◽

Hedonic Processing

It has been hypothesized that the pleasure of a reward in humans is mediated by an opioidergic system involving the hypothalamus, nucleus accumbens and the amygdala. Importantly, enjoying the pleasure of a reward is distinct from incentive salience induced by cues predicting the reward. We investigated this issue using a within subject, pharmacological challenge design with the opioid receptor antagonist naloxone and fMRI. Our data show that blocking opioid receptors reduced pleasure associated with viewing erotic pictures more than viewing symbols of reward such as money. This was paralleled by a reduction of activation in the ventral striatum, lateral orbitofrontal cortex, amygdala, hypothalamus and medial prefrontal cortex. Crucially, the naloxone induced activation decrease was observed at reward delivery, but not during reward anticipation, indicating that blocking opioid receptors decreases the pleasure of rewards in humans.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

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