TY - JOUR
T1 - Activation of extrasynaptic NMDARs at individual parallel fiber-molecular layer interneuron synapses in cerebellum
AU - Nahir, Ben
AU - Jahr, Craig E.
PY - 2013
Y1 - 2013
N2 - NMDA receptors (NMDARs) expressed by cerebellar molecular layer interneurons (MLIs) are not activated by single exocytotic events but can respond to glutamate spillover following coactivation of adjacent parallel fibers (PFs), indicating that NMDARs are perisynaptic. Several types of synaptic plasticity rely on these receptors but whether they are activated at isolated synapses is not known. Using a combination of electrophysiological and optical recording techniques in acute slices of rat cerebellum, along with modeling, we find that repetitive activation of single PF-MLI synapses can activate NMDARs in MLIs. High-frequency stimulation, multivesicular release (MVR), or asynchronous release can each activate NMDARs. Frequency facilitation was found at all PF-MLI synapses but, while some showed robust MVR with increased release probability, most were limited to univesicular release. Together, these results reveal a functional diversity of PF synapses, which use different mechanisms to activate NMDARs.
AB - NMDA receptors (NMDARs) expressed by cerebellar molecular layer interneurons (MLIs) are not activated by single exocytotic events but can respond to glutamate spillover following coactivation of adjacent parallel fibers (PFs), indicating that NMDARs are perisynaptic. Several types of synaptic plasticity rely on these receptors but whether they are activated at isolated synapses is not known. Using a combination of electrophysiological and optical recording techniques in acute slices of rat cerebellum, along with modeling, we find that repetitive activation of single PF-MLI synapses can activate NMDARs in MLIs. High-frequency stimulation, multivesicular release (MVR), or asynchronous release can each activate NMDARs. Frequency facilitation was found at all PF-MLI synapses but, while some showed robust MVR with increased release probability, most were limited to univesicular release. Together, these results reveal a functional diversity of PF synapses, which use different mechanisms to activate NMDARs.
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U2 - 10.1523/JNEUROSCI.1971-13.2013
DO - 10.1523/JNEUROSCI.1971-13.2013
M3 - Article
C2 - 24107963
AN - SCOPUS:84885140903
SN - 0270-6474
VL - 33
SP - 16323
EP - 16333
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 41
ER -