Taurine in deep cerebellar nuclei of the rat. In vivo comparison to GABA inhibitory effect

Purkinje cells (PCs) integrate all computations performed in the cerebellar cortex to inhibit neurons in the deep cerebellar nuclei (DCN). Simple spikes recorded in vivo from pairs of PCs separated by <100 μm are known to be synchronized with a sharp peak riding on a broad peak, but the significance of this finding is unclear. We show that the sharp peak consists exclusively of simple spikes associated with pauses in firing. The broader, less precise peak was caused by firing-rate co-modulation of faster firing spikes. About 13% of all pauses were synchronized, and these pauses had a median duration of 20 ms. As in vitro studies have reported that synchronous pauses can reliably trigger spikes in DCN neurons, we suggest that the subgroup of spikes causing the sharp peak is important for precise temporal coding in the cerebellum.

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Unusually slow spike frequency adaptation in deep cerebellar nuclei neurons preserves linear transformations on the sub-second time scale

10.1101/2021.08.10.455865 ◽

2021 ◽

Author(s):

Mehak M Khan ◽

Christopher H Chen ◽

wade G regehr

Keyword(s):

Brain Slices ◽

Cerebellar Nuclei ◽

Spike Frequency ◽

Initial Increase ◽

Projection Neurons ◽

Spike Frequency Adaptation ◽

Linear Transformations ◽

Deep Cerebellar Nuclei ◽

Frequency Adaptation

Purkinje cells (PCs) are spontaneously active neurons of the cerebellar cortex that inhibit glutamatergic projection neurons within the deep cerebellar nuclei (DCN) that in turn provide the primary cerebellar output. Brief reductions in PC firing rapidly increase DCN neuron firing. However, prolonged reductions in PC inhibition, as seen in some disease states, certain types of transgenic mice, and in acute slices of the cerebellum, do not evoke large sustained increases in DCN firing. Here we test whether there is a mechanism of spike-frequency adaptation in DCN neurons that could account for these properties. We find that prolonged optogenetic suppression of PC synapses in vivo transiently elevates PC firing that strongly adapts within ten seconds. We perform current-clamp recordings at near physiological temperature in acute brain slices to examine how DCN neurons respond to prolonged depolarizations. Adaptation in DCN neurons is exceptionally slow and bidirectional. A depolarizing current step evokes large initial increases in firing that decay to less than 20% of the initial increase within approximately ten seconds. Such slow adaptation could allow DCN neurons to adapt to prolonged changes in PC firing while maintaining their linear firing frequency-current relationship on subsecond time scales.

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Long-Lasting Response Changes in Deep Cerebellar Nuclei in vivo Correlate With Low-Frequency Oscillations

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2019.00084 ◽

2019 ◽

Vol 13 ◽

Cited By ~ 4

Author(s):

Letizia Moscato ◽

Ileana Montagna ◽

Licia De Propris ◽

Simona Tritto ◽

Lisa Mapelli ◽

...

Keyword(s):

Low Frequency ◽

Cerebellar Nuclei ◽

Deep Cerebellar Nuclei ◽

Low Frequency Oscillations

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Deep Cerebellar Nuclei Rebound Firing In Vivo

The Neuronal Codes of the Cerebellum ◽

10.1016/b978-0-12-801386-1.00002-2 ◽

2016 ◽

pp. 27-51 ◽

Cited By ~ 2

Author(s):

Davide Reato ◽

Esra Tara ◽

Kamran Khodakhah

Keyword(s):

Cerebellar Nuclei ◽

Deep Cerebellar Nuclei ◽

Rebound Firing

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Anatomical and functional relationships between deep cerebellar nuclei and cerebellar cortical Crus II in vivo in mice

Neuroscience Letters ◽

10.1016/j.neulet.2015.10.064 ◽

2016 ◽

Vol 610 ◽

pp. 73-78 ◽

Cited By ~ 1

Author(s):

Nan Ding ◽

Hua Jin ◽

Bin-Bin Zhang ◽

Ao Guo ◽

Jin-Di Shi ◽

...

Keyword(s):

Cerebellar Nuclei ◽

Deep Cerebellar Nuclei ◽

Functional Relationships

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The Inhibition of Platelet Aggregation by an Aorta Intima Extract

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647710 ◽

1974 ◽

Vol 32 (02/03) ◽

pp. 417-431 ◽

Cited By ~ 14

Author(s):

A. du P Heyns ◽

D. J van den Berg ◽

G. M Potgieter ◽

F. P Retief

Keyword(s):

Platelet Aggregation ◽

Degradation Products ◽

Adenosine Diphosphate ◽

Inhibitory Effect ◽

Protective Role ◽

Vascular Trauma ◽

Wear And Tear ◽

Sequential Addition ◽

Aggregation Activity

SummaryThe platelet aggregating activity of extracts of different layers of the arterial wall was compared to that of Achilles tendon. Arterial media and tendon extracts, adjusted to equivalent protein content as an index of concentration, aggregated platelets to the same extent but an arterial intima extract did not aggregate platelets. Platelet aggregation induced by collagen could be inhibited by mixing with intima extract, but only to a maximum of about 80%. Pre-mixing adenosine diphosphate (ADP) with intima extracts diminished the platelet aggregation activity of the ADP. Depending on the relationship between ADP and intima extract concentrations aggregating activity could either be completely inhibited or inhibition abolished. Incubation of ADP with intima extract and subsequent separation of degradation products by paper chromatography, demonstrated a time-dependent breakdown of ADP with AMP, adenosine, inosine and hypoxanthine as metabolic products; ADP removal was complete. Collagen, thrombin and adrenaline aggregate platelets mainly by endogenous ADP of the release reaction. Results of experiments comparing inhibition of aggregation caused by premixing aggregating agent with intima extract, before exposure to platelets, and the sequential addition of first the intima extract and then aggregating agent to platelets, suggest that the inhibitory effect of intima extract results from ADP breakdown. It is suggested that this ADP degradation by intima extract may play a protective role in vivo by limiting the size of platelet aggregates forming at the site of minimal “wear and tear” vascular trauma.

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Measurement of the Platelet Response to Laser- induced Microvascular Injury

Thrombosis and Haemostasis ◽

10.1055/s-0038-1648118 ◽

1974 ◽

Vol 32 (02/03) ◽

pp. 704-713 ◽

Cited By ~ 2

Author(s):

F. N McKenzie ◽

K.-E Arfors ◽

N. A Matheson

Keyword(s):

Inhibitory Effect ◽

Microvascular Blood Flow ◽

Platelet Response ◽

High Concentration ◽

Platelet Activity ◽

Microvascular Injury ◽

Arterial Blood ◽

Proximal Site ◽

Adenosine Phosphates

SummaryA study has been made of the biochemical factors underlying the platelet response to laser-induced microvascular injury. A platelet aggregating substance is produced at sites of laser-induced injury which markedly stimulates platelet activity at a site of injury inflicted a short distance downstream. Distal sites of injury are not similarly influenced if the distance between the injuries is increased or if the proximal site no longer shows platelet-stimulating activity. The stimulating effect of an adjacent proximal injury on platelet activity at a distal site is inhibited by local intra-arterial infusion of adenosine. Measurements of arterial blood pressure and microvascular blood flow velocity during adenosine infusion showed that its inhibitory effect on platelet activity is largely independent of its vasodilator properties. The effect of infusion of different adenosine phosphates (AMP, ADP, ATP) was also studied. Very small amounts of ADP markedly stimulated platelet activity and the emboli formed were similar to those normally produced at sites of laser injury. At high concentration AMP inhibited while ATP stimulated platelet activity in vivo. The results emphasise the fundamental role of ADP as a mediator of the platelet response at sites of laser- induced microvascular injury.

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The Effects of Heparin and Annexin V on Fibrin Accretion after Injury in the Jugular Veins of Rabbits

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651585 ◽

1993 ◽

Vol 69 (03) ◽

pp. 227-230 ◽

Cited By ~ 28

Author(s):

J Van Ryn-McKenna ◽

H Merk ◽

T H Müller ◽

M R Buchanan ◽

W G Eisert

Keyword(s):

Vessel Wall ◽

Thrombin Generation ◽

Antithrombin Iii ◽

Specific Effect ◽

Annexin V ◽

Inhibitory Effect ◽

Jugular Veins ◽

Prothrombinase Complex ◽

Wall Injury

SummaryWe compared the relative abilities of unfractionated heparin and annexin V to prevent fibrin accretion onto injured jugular veins in vivo. Heparin was used to accelerate the inhibition of thrombin by antithrombin III, and annexin V was used to inhibit the assembly of the prothrombinase complex on phospholipid surfaces, thereby blocking thrombin generation. Rabbit jugular veins were isolated in situ, a 2 cm segment was injured by perfusing it with air, and then blood flow was re-established. Five minutes later, each rabbit was injected with heparin (20 U/kg) or annexin V (0.3 mg/kg) and then with 125I-fibrinogen. The amount of 125I-fibrin accumulation onto each injured vessel wall segment was measured 4 h later. Each injured vessel was completely deendothelialized as a result of the air perfusion as demonstrated by electron microscopy. 125I-fibrin accretion onto the injured jugular veins was enhanced 2.4-fold as compared to the uninjured veins in sham-operated animals. Heparin treatment did not reduce fibrin accretion, whereas, annexin V treatment decreased fibrin accretion by 60%, p <0.05. This latter effect was achieved without sustained circulating anticoagulation. Additional experiments confirmed that the inhibitory effect of annexin V on fibrin accretion was associated with a surface specific effect, since more annexin V bound to the injured jugular vein segments as compared to the non-injured jugular veins. We conclude that, i) mild vessel wall injury (selective de-endothelialization) in veins results in a thrombogenic vessel wall; ii) the thrombogenecity of which is not inhibited by prophylactic doses of heparin; but iii) is inhibited by annexin V, which binds to injured vessel wall surface, and inhibits thrombin generation independently of antithrombin III.

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The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649080 ◽

1973 ◽

Vol 30 (02) ◽

pp. 315-326

Author(s):

J. Heinz Joist ◽

Jean-Pierre Cazenave ◽

J. Fraser Mustard

Keyword(s):

Platelet Aggregation ◽

Platelet Function ◽

Barbituric Acid ◽

Platelet Rich Plasma ◽

Inhibitory Effect ◽

Primary Response ◽

Sodium Pentobarbital ◽

Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

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