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

2000 ◽  
Vol 84 (3) ◽  
pp. 1414-1421 ◽  
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.

Postsynaptic mechanisms underlying long-term depression of GABAergic transmission in neurons of the deep cerebellar nuclei

1996 ◽  
Vol 76 (1) ◽  
pp. 59-68 ◽  
Author(s):  
W. Morishita ◽  
B. R. Sastry
Keyword(s):  
Synaptic Transmission ◽  
Gabaa Receptor ◽  
Cell Voltage ◽  
Cerebellar Nuclei ◽  
Neuronal Membrane ◽  
Gamma Aminobutyric Acid ◽  
Deep Cerebellar Nuclei ◽  
Long Term Depression ◽  
In Cells

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.

Interaction Between Tetanus Long-Term Potentiation and Hypoxia-Induced Potentiation in the Rat Hippocampus

1997 ◽  
Vol 78 (5) ◽  
pp. 2475-2482 ◽  
Author(s):  
M. Lyubkin ◽  
D. M. Durand ◽  
M. A. Haxhiu
Keyword(s):  
Synaptic Transmission ◽  
Long Term Potentiation ◽  
Rat Hippocampus ◽  
Magnesium Concentration ◽  
High Frequency Stimulation ◽  
Excitatory Postsynaptic Potential ◽  
Synaptic Specificity ◽  
Term Potentiation ◽  
Neuronal Processing

Lyubkin, M., D. M. Durand, and M. A. Haxhiu. Interaction between tetanus long-term potentiation and hypoxia-induced potentiation in the rat hippocampus. J. Neurophysiol. 78: 2475–2482, 1997. The interaction between tetanus-induced long-term potentiation (LTP) and hypoxia-induced potentiation was investigated by performing extracellular recordings in the CA1 region of rat hippocampus using a two-pathway design. Hippocampal slices were placed in an interface chamber containing artificial cerebrospinal fluid (ACSF) solution with high magnesium concentration. Hypoxia was induced by replacing the 5% CO2-95% O2 gas mixture with 5% CO2-95% N2 for 2 min. Tetanus-LTP was induced with 1-s, 100-Hz current pulses. Significant hypoxia-induced potentiation of the slope of the dendritic excitatory postsynaptic potential (EPSP) was found in ACSF containing 2 mM of magnesium 2, 27 ± 10% (mean ± SE; n = 16; P < 0.01) with no change in the mean amplitude of the presynaptic volley. All experiments in which a stable control baseline was obtained were used for data analysis. The data show that short episodes (2 min) of hypoxia can induce LTP of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-mediated synaptic transmission. The present study demonstrated that after tetanus-LTP, 33 ± 3% ( n = 10; P < 0.01), hypoxia further potentiated the field EPSP slopes by a mean value of 16 ± 5% ( n = 10; P < 0.05). Moreover, using a two-pathway design, we showed that hypoxia produced similar potentiation in both the control [19 ± 5%; n = 10; P < 0.01) and tetanus-induced LTP pathway, and the total potentiation produced by a combination of tetanus then hypoxia, 63 ± 13% ( n = 10; p < 0.01), was significantly larger ( P < 0.01) than hypoxia alone. These data suggest that hypoxia-induced potentiation is additive with tetanus-LTP. Occlusion experiments were performed to verify whether the mechanisms responsible for hypoxia-induced potentiation are independent of preexisting synaptic levels induced by high-frequency stimulation. Hypoxia produced significant potentiation (23 ± 7%; n = 7; P < 0.05) after successful occlusion of the LTP pathway. Therefore, because the magnitude of hypoxia-induced potentiation is both independent of preexisting synaptic levels and also additive, synaptic specificity associated with LTP is preserved. The magnitude of tetanus-LTP induced 20 min after hypoxia (15 ± 4%; n = 10) was significantly smaller ( P < 0.01) relative to LTP after normoxic conditions (33 ± 3%; n = 10). Additionally, hypoxia blocked the transient, robust potentiation occurring during the early phase of LTP induction. This study suggests that although hypoxia modifies neuronal processing by general excitation, synaptic specificity associated with tetanus-LTP still is preserved. However, hypoxia can disrupt neuronal processing by inhibiting new modification of synaptic transmission.

Synaptic Transmission and Hippocampal Long-Term Potentiation in Olfactory Cyclic Nucleotide-Gated Channel Type 1 Null Mouse

1998 ◽  
Vol 79 (6) ◽  
pp. 3295-3301 ◽  
Author(s):  
Angèle Parent ◽  
Karen Schrader ◽  
Steven D. Munger ◽  
Randall R. Reed ◽  
David J. Linden ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Cyclic Nucleotide ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Null Mouse ◽  
Term Potentiation ◽  
Gated Channel ◽  
Frequency Stimulation

Parent, Angèle, Karen Schrader, Steven D. Munger, Randall R. Reed, David J. Linden, and Gabriele V. Ronnett. Synaptic transmission and hippocampal long-term potentiation in olfactory cyclic nucleotide-gated channel type 1 null mouse. J. Neurophysiol. 79: 3295–3301, 1998. Field potential recording was used to investigate properties of synaptic transmission and long-term potentiation (LTP) at Schaffer collateral-CA1 synapses in both hippocampal slices of mutant mice in which the α-subunit of the olfactory cyclic nucleotide-gated channel (α3/OCNC)1 was rendered null and also in slices prepared from their wild-type (Wt) littermates. Several measures of basal synaptic transmission were unaltered in the OCNC1 knockout (KO), including maximum field excitatory postsynaptic potential (fEPSP) slope, maximum fEPSP and fiber volley amplitude, and the function relating fiber volley amplitude to fEPSP slope and paired-pulse facilitation. When a high-frequency stimulation protocol was used to induce LTP, similar responses were seen in both groups [KO: 1 min, 299 ± 50% (mean ± SE), 60 min, 123 ± 10%; Wt: 1 min, 287 ± 63%; 60 min, 132 ± 19%). However, on theta-burst stimulation, the initial amplitude of LTP was smaller (1 min after induction, 147 ± 16% of baseline) and the response decayed faster in the OCNC1 KO (60 min, 127 ± 18%) than in Wt (1 min, 200 ± 14%; 60 min, 169 ± 19%). Analysis of waveforms evoked by LTP-inducing tetanic stimuli revealed a similar difference between groups. The development of potentiation throughout the tetanic stimulus was similar in OCNC1 KO and Wt mice when high-frequency stimulation was used, but OCNC1 KO mice showed a significant decrease when compared with Wt mice receiving theta-burst stimulation. These results suggest that activation of cyclic nucleotide-gated channels may contribute to the induction of LTP by weaker, more physiological stimuli, possibly via Ca2+ influx.

scholarly journals SCH23390 Reduces Methamphetamine Self-Administration and Prevents Methamphetamine-Induced Striatal LTD

2020 ◽  
Vol 21 (18) ◽  
pp. 6491
Author(s):  
Yosef Avchalumov ◽  
Wulfran Trenet ◽  
Juan Piña-Crespo ◽  
Chitra Mandyam
Keyword(s):  
Synaptic Transmission ◽  
Ex Vivo ◽  
Dorsal Striatum ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Self Administration ◽  
Striatal Slices ◽  
Extended Access

Extended-access methamphetamine self-administration results in unregulated intake of the drug; however, the role of dorsal striatal dopamine D1-like receptors (D1Rs) in the reinforcing properties of methamphetamine under extended-access conditions is unclear. Acute (ex vivo) and chronic (in vivo) methamphetamine exposure induces neuroplastic changes in the dorsal striatum, a critical region implicated in instrumental learning. For example, methamphetamine exposure alters high-frequency stimulation (HFS)-induced long-term depression in the dorsal striatum; however, the effect of methamphetamine on HFS-induced long-term potentiation (LTP) in the dorsal striatum is unknown. In the current study, dorsal striatal infusion of SCH23390, a D1R antagonist, prior to extended-access methamphetamine self-administration reduced methamphetamine addiction-like behavior. Reduced behavior was associated with reduced expression of PSD-95 in the dorsal striatum. Electrophysiological findings demonstrate that superfusion of methamphetamine reduced basal synaptic transmission and HFS-induced LTP in dorsal striatal slices, and SCH23390 prevented this effect. These results suggest that alterations in synaptic transmission and synaptic plasticity induced by acute methamphetamine via D1Rs could assist with methamphetamine-induced modification of corticostriatal circuits underlying the learning of goal-directed instrumental actions and formation of habits, mediating escalation of methamphetamine self-administration and methamphetamine addiction-like behavior.

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