Long-term depression of IPSPs in rat deep cerebellar nuclei

1. The mechanisms underlying long-term depression (LTD) of gamma-aminobutyric acid-A (GABAA) receptor-mediated synaptic transmission induced by 10-Hz stimulation of the inhibitory afferents were investigated using perforated and whole cell voltage-clamp recordings from neurons of the deep cerebellar nuclei (DCN). 2. LTD of inhibitory postsynaptic currents (IPSCs) was reliably induced when the 10-Hz stimulation was delivered under current-clamp conditions where the postsynaptic neuronal membrane was allowed to depolarize. 3. Currents elicited by local applications of the GABAA receptor agonist, 4,5,6,7-tetrahydroisoxazolo [5,4-c]pyridin-3-ol hydrochloride (THIP) were also depressed during LTD. 4. LTD could be induced heterosynaptically and did not require the activation of GABAA receptors during the 10-Hz stimulation. 5. In cells loaded with QX-314 and superfused with media containing 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2-amino-5-phosphonovaleric acid (APV), a series of depolarizing pulses (50 mV, 200 ms) induced a sustained depression of the IPSC. However, this was not observed in cells recorded with high bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA)-containing pipette solutions or when they were exposed to the L-type Ca2+ channel antagonist, nitrendipine. 6. The 10-Hz-induced LTD was also inhibited by BAPTA and was significantly reduced when DCN cells were loaded with microcystin LR or treated with okadaic acid, both inhibitors of protein phosphatases. 7. These results indicate that increases in postsynaptic [Ca2+] and phosphatase activity can reduce the efficacy of GABAA receptor-mediated synaptic transmission.

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Modulatory effects of serotonin on glutamatergic synaptic transmission and long-term depression in the deep cerebellar nuclei

Neuroscience ◽

10.1016/j.neuroscience.2010.10.037 ◽

2011 ◽

Vol 172 ◽

pp. 118-128 ◽

Cited By ~ 14

Author(s):

M. Murano ◽

F. Saitow ◽

H. Suzuki

Keyword(s):

Synaptic Transmission ◽

Cerebellar Nuclei ◽

Deep Cerebellar Nuclei ◽

Long Term Depression ◽

Glutamatergic Synaptic Transmission

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Mapping of long-term cognitive and motor deficits in pediatric cerebellar brain tumor survivors into a cerebellar white matter atlas

Child s Nervous System ◽

10.1007/s00381-021-05244-2 ◽

2021 ◽

Author(s):

Frederik Grosse ◽

Stefan Mark Rueckriegel ◽

Ulrich-Wilhelm Thomale ◽

Pablo Hernáiz Driever

Keyword(s):

Brain Tumor ◽

Executive Function ◽

Cognitive Function ◽

White Matter ◽

Cerebellar Nuclei ◽

Motor Deficits ◽

Deep Cerebellar Nuclei ◽

Cerebellar White Matter ◽

Lesion Symptom Mapping

Abstract Purpose Diaschisis of cerebrocerebellar loops contributes to cognitive and motor deficits in pediatric cerebellar brain tumor survivors. We used a cerebellar white matter atlas and hypothesized that lesion symptom mapping may reveal the critical lesions of cerebellar tracts. Methods We examined 31 long-term survivors of pediatric posterior fossa tumors (13 pilocytic astrocytoma, 18 medulloblastoma). Patients underwent neuronal imaging, examination for ataxia, fine motor and cognitive function, planning abilities, and executive function. Individual consolidated cerebellar lesions were drawn manually onto patients’ individual MRI and normalized into Montreal Neurologic Institute (MNI) space for further analysis with voxel-based lesion symptom mapping. Results Lesion symptom mapping linked deficits of motor function to the superior cerebellar peduncle (SCP), deep cerebellar nuclei (interposed nucleus (IN), fastigial nucleus (FN), ventromedial dentate nucleus (DN)), and inferior vermis (VIIIa, VIIIb, IX, X). Statistical maps of deficits of intelligence and executive function mapped with minor variations to the same cerebellar structures. Conclusion We identified lesions to the SCP next to deep cerebellar nuclei as critical for limiting both motor and cognitive function in pediatric cerebellar tumor survivors. Future strategies safeguarding motor and cognitive function will have to identify patients preoperatively at risk for damage to these critical structures and adapt multimodal therapeutic options accordingly.

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Effect of Long-Term Retention of Gadolinium on Metabolism of Deep Cerebellar Nuclei After Repeated Injections of Gadodiamide in Rats

Investigative Radiology ◽

10.1097/rli.0000000000000621 ◽

2020 ◽

Vol 55 (2) ◽

pp. 120-128 ◽

Cited By ~ 3

Author(s):

Dounia El Hamrani ◽

Véronique Vives ◽

Rebecca Buchholz ◽

William Même ◽

Cecile Factor ◽

...

Keyword(s):

Cerebellar Nuclei ◽

Deep Cerebellar Nuclei ◽

Term Retention ◽

Long Term Retention

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Mechanisms Underlying LTP of Inhibitory Synaptic Transmission in the Deep Cerebellar Nuclei

Journal of Neurophysiology ◽

10.1152/jn.2000.84.3.1414 ◽

2000 ◽

Vol 84 (3) ◽

pp. 1414-1421 ◽

Cited By ~ 74

Author(s):

Mohamed Ouardouz ◽

Bhagavatula R. Sastry

Keyword(s):

Synaptic Transmission ◽

Motor Coordination ◽

Reversal Potential ◽

Long Term Potentiation ◽

Cerebellar Nuclei ◽

High Frequency Stimulation ◽

Deep Cerebellar Nuclei ◽

Inhibitory Synaptic Transmission ◽

Nmda Glutamate Receptor Antagonist

Whole-cell recordings were used to investigate long-term potentiation of inhibitory synaptic currents (IPSCs) in neurons of deep cerebellar nuclei (DCN) in slices. IPSCs were evoked by electrical stimulation of the white matter surrounding the DCN in the presence of non- N-methyl-d-aspartate (non-NMDA) glutamate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (20 μM). High-frequency stimulation induced a long-term potentation (LTP) of the IPSC amplitude without changing its reversal potential, rise time, and decay-time constant. This LTP did not require the activation of postsynaptic γ-aminobutyric acid-A (GABAA) receptors but depended on the activation of NMDA receptors. LTP of IPSCs in DCN neurons could also be induced by voltage-depolarizing pulses in postsynaptic neurons and appeared to depend on an increase in intracellular calcium as the LTP was blocked when the cells were loaded with a calcium chelator, 1,2-bis-(2-amino-phenoxy)- N, N, N′, N′-tetraacetic acid (BAPTA, 10 mM). LTP of IPSCs was accompanied by an increase in the frequency of spontaneous IPSCs and miniature IPSCs (recorded in the presence of tetrodotoxin 1 μM), but there was no significant change in their amplitude. In addition, during the LTP, the amplitude of response to exogenously applied GABAA receptor agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol hydrochloride was increased. Intracellular application of tetanus toxin, a powerful blocker of exocytosis, in DCN neuron prevented the induction of LTP of IPSCs. Our results suggest that the induction of LTP of IPSCs in the DCN neurons likely involves a postsynaptic locus. Plasticity of inhibitory synaptic transmission in DCN neurons may play a crucial role in cerebellar control of motor coordination and learning.

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