TY - JOUR
T1 - Deactivation of l-type ca current by inhibition controls ltp at excitatory synapses in the cerebellar nuclei
AU - Person, Abigail L.
AU - Raman, Indira M.
N1 - Funding Information:
Supported by NIH NS39395 (I.M.R.). A.L.P. was supported by T32 NS041234 and F32 NS067831. We thank Jason Pugh for helpful comments on the manuscript.
PY - 2010/5
Y1 - 2010/5
N2 - Long-term potentiation (LTP) of mossy fiber EPSCs in the cerebellar nuclei is controlled by synaptic inhibition from Purkinje neurons. EPSCs are potentiated by a sequence of excitation, inhibition, and disinhibition, raising the question of how these stimuli interact to induce plasticity. Here, we find that synaptic excitation, inhibition, and disinhibition couple to different calcium-dependent signaling pathways. In LTP induction protocols, constitutively active calcineurin can replace synaptic excitation, and constitutively active α-CaMKII can replace calcium influx associated with resumption of spiking upon disinhibition. Additionally, nimodipine can replace hyperpolarization, indicating that inhibition of firing decreases Ca influx through L-type Ca channels, providing a necessary signal for LTP. Together, these data suggest that potentiation develops after a calcineurin priming signal combines with an α-CaMKII triggering signal if and only if L-type Ca current is reduced. Thus, hyperpolarization induced by synaptic inhibition actively controls excitatory synaptic plasticity in the cerebellar nuclei.
AB - Long-term potentiation (LTP) of mossy fiber EPSCs in the cerebellar nuclei is controlled by synaptic inhibition from Purkinje neurons. EPSCs are potentiated by a sequence of excitation, inhibition, and disinhibition, raising the question of how these stimuli interact to induce plasticity. Here, we find that synaptic excitation, inhibition, and disinhibition couple to different calcium-dependent signaling pathways. In LTP induction protocols, constitutively active calcineurin can replace synaptic excitation, and constitutively active α-CaMKII can replace calcium influx associated with resumption of spiking upon disinhibition. Additionally, nimodipine can replace hyperpolarization, indicating that inhibition of firing decreases Ca influx through L-type Ca channels, providing a necessary signal for LTP. Together, these data suggest that potentiation develops after a calcineurin priming signal combines with an α-CaMKII triggering signal if and only if L-type Ca current is reduced. Thus, hyperpolarization induced by synaptic inhibition actively controls excitatory synaptic plasticity in the cerebellar nuclei.
KW - Molneuro
UR - http://www.scopus.com/inward/record.url?scp=77953239957&partnerID=8YFLogxK
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U2 - 10.1016/j.neuron.2010.04.024
DO - 10.1016/j.neuron.2010.04.024
M3 - Article
C2 - 20510859
AN - SCOPUS:77953239957
VL - 66
SP - 550
EP - 559
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 4
ER -