scholarly journals Kinetic, pharmacological and activity-dependent separation of two Ca2+signalling pathways mediated by type 1 metabotropic glutamate receptors in rat Purkinje neurones

2006 ◽  
Vol 573 (1) ◽  
pp. 65-82 ◽  
Author(s):  
Marco Canepari ◽  
David Ogden
2012 ◽  
Vol 107 (4) ◽  
pp. 1058-1066 ◽  
Author(s):  
Peng Zhang ◽  
John E. Lisman

CaMKII and PSD-95 are the two most abundant postsynaptic proteins in the postsynaptic density (PSD). Overexpression of either can dramatically increase synaptic strength and saturate long-term potentiation (LTP). To do so, CaMKII must be activated, but the same is not true for PSD-95; expressing wild-type PSD-95 is sufficient. This raises the question of whether PSD-95's effects are simply an equilibrium process [increasing the number of AMPA receptor (AMPAR) slots] or whether activity is somehow involved. To examine this question, we blocked activity in cultured hippocampal slices with TTX and found that the effects of PSD-95 overexpression were greatly reduced. We next studied the type of receptors involved. The effects of PSD-95 were prevented by antagonists of group I metabotropic glutamate receptors (mGluRs) but not by antagonists of ionotropic glutamate receptors. The inhibition of PSD-95-induced strengthening was not simply a result of inhibition of PSD-95 synthesis. To understand the mechanisms involved, we tested the role of CaMKII. Overexpression of a CaMKII inhibitor, CN19, greatly reduced the effect of PSD-95. We conclude that PSD-95 cannot itself increase synaptic strength simply by increasing the number of AMPAR slots; rather, PSD-95's effects on synaptic strength require an activity-dependent process involving mGluR and CaMKII.


2001 ◽  
Vol 13 (8) ◽  
pp. 1469-1478 ◽  
Author(s):  
Valeria Bruno ◽  
Giuseppe Battaglia ◽  
Agata Copani ◽  
Virtudes M. Cespédes ◽  
María F. Galindo ◽  
...  

2015 ◽  
Vol 41 (4) ◽  
pp. 924-932 ◽  
Author(s):  
Maria Rosaria Romano ◽  
Luisa Di Menna ◽  
Pamela Scarselli ◽  
Giada Mascio ◽  
Michele Madonna ◽  
...  

2000 ◽  
Vol 83 (3) ◽  
pp. 1141-1149 ◽  
Author(s):  
G. R. Dubé ◽  
K. C. Marshall

Synaptic activation of metabotropic glutamate receptors (mGluRs) in the locus coeruleus (LC) was investigated in adult rat brain slice preparations. Evoked excitatory postsynaptic potentials (EPSPs) resulting from stimulation of LC afferents were measured with current clamp from intracellularly recorded LC neurons. In this preparation, mGluR agonists (±)-1-aminocyclopentane- trans-1,3-dicarboxylic acid ( t-ACPD) and L(+)-2-amino-4-phosphonobutyric acid (L-AP4) activate distinct presynaptic mGluRs, resulting in an inhibition of EPSPs. When two stimuli were applied to afferents at intervals >200 ms, the amplitude of the second [test (T)] EPSP was identical in amplitude to the first [control(C)]. However, when a stimulation volley was delivered before T, the amplitude of the latter EPSP was consistently smaller than C. The activity-dependent depression (ADD) was dependent on the frequency and duration of the train and the interval between the train and T. ADD was potentiated in the presence of an excitatory amino acid (EAA) uptake inhibitorL- trans-pyrrolidine-2,4-dicarboxylic acid ( t-PDC, 100 μM), changing the T/C ratio from 0.84 ± 0.05 (mean ± SE) in control to 0.69 ± 0.04 in t-PDC ( n = 9). In the presence of t-PDC, the depolarizing response of LC neurons to focally applied glutamate was also increased. Together, these results suggest that accumulation of EAA after synaptic stimulation may be responsible for ADD. To test if ADD is a result of the activation of presynaptic mGluRs, the effect of selective mGluR antagonists on ADD was assessed. In the presence of t-PDC, bath applied (S)-amino-2-methyl-4-phosphonobutanoic acid (MAP4, 500 μM), a mGluR group III antagonist, significantly reversed the decrease in T/C ratio after a train stimulation [from 0.66 ± 0.04 to 0.81 ± 0.02 (mean ± SE), n = 5]. The T/C ratio in the presence of MAP4 was not different from that measured in the absence of a stimulation volley. Conversely, ethyl glutamic acid (EGLU, 500 μM), a mGluR group II antagonist, failed to alter the T/C ratio. Together, these results suggest that, in LC, group III presynaptic mGluR activation provides a feedback mechanism by which excitatory synaptic transmission can be negatively modulated during high-frequency synaptic activity. Furthermore, this study provides functional differentiation between presynaptic groups II and III mGluR in LC and suggests that the group II mGluR may be involved in functions distinct from those of group III mGluRs.


2016 ◽  
Vol 263 (11) ◽  
pp. 2179-2187 ◽  
Author(s):  
Kenji Ishibashi ◽  
Yoshiharu Miura ◽  
Kinya Ishikawa ◽  
Ming-Rong Zhang ◽  
Jun Toyohara ◽  
...  

2001 ◽  
Vol 17 (6) ◽  
pp. 1071-1083 ◽  
Author(s):  
Giuseppe Battaglia ◽  
Valeria Bruno ◽  
Antonio Pisani ◽  
Diego Centonze ◽  
Maria Vincenza Catania ◽  
...  

2011 ◽  
Vol 81 (1) ◽  
pp. 12-20 ◽  
Author(s):  
Simona Federica Spampinato ◽  
Gemma Molinaro ◽  
Sara Merlo ◽  
Luisa Iacovelli ◽  
Filippo Caraci ◽  
...  

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