Enhanced Excitatory Transmission at Cortical Synapses as the Basis for Facilitated Spreading Depression in Cav2.1 Knockin Migraine Mice

被引：252

作者：

Tottene, Angelita ^{[1
,2
]}

Conti, Rossella ^{[1
,2
]}

Fabbro, Alessandra ^{[1
,2
]}

Vecchia, Dania ^{[1
,2
]}

Shapovalova, Maryna ^{[1
,2
]}

Santello, Mirko ^{[1
,2
]}

van den Maagdenberg, Arn M. J. M. ^{[3
,4
]}

Ferrari, Michel D. ^{[3
]}

Pietrobon, Daniela ^{[1
,2
]}

机构：

[1] Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy

[2] CNR, Inst Neurosci, I-35121 Padua, Italy

[3] Leiden State Univ, Med Ctr, Dept Neurol, NL-2333 AL Leiden, Netherlands

[4] Leiden State Univ, Med Ctr, Dept Human Genet, NL-2333 AL Leiden, Netherlands

来源：

NEURON | 2009年 / 61卷 / 05期

关键词：

FAMILIAL HEMIPLEGIC MIGRAINE; CURRENT SOURCE DENSITY; NEOCORTEX IN-VITRO; CALCIUM-CHANNELS; PYRAMIDAL CELLS; TRANSMITTER RELEASE; P/Q-TYPE; ELECTROGRAPHIC SEIZURES; DEPENDENT DEPRESSION; SYNAPTIC PLASTICITY;

D O I：

10.1016/j.neuron.2009.01.027

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Migraine is a common disabling brain disorder. A subtype of migraine with aura (familial hemiplegic migraine type 1: FHM1) is caused by mutations in Ca(v)2.1 (P/Q-type) Ca2+ channels. Knockin mice carrying a FHM1 mutation show increased neuronal P/Q-type current and facilitation of induction and propagation of cortical spreading depression (CSD), the phenomenon that underlies migraine aura and may activate migraine headache mechanisms. We studied cortical neurotransmission in neuronal microcultures and brain slices of FHM1 mice. We show gain of function of excitatory neurotransmission due to increased action-potential-evoked Ca2+ influx and increased probability of glutamate release at pyramidal cell synapses but unaltered inhibitory neurotransmission at fast-spiking interneuron synapses. Using an in vitro model of CSD, we show a causative link between enhanced glutamate release and CSD facilitation. The synapse-specific effect of FHM1 mutations points to disruption of excitation-inhibition balance and neuronal hyperactivity as the basis for episodic vulnerability to CSD ignition in migraine.

引用

页码：762 / 773

页数：12

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