Unaltered Network Activity and Interneuronal Firing During Spontaneous Cortical Dynamics In Vivo in a Mouse Model of Severe Myoclonic Epilepsy of Infancy
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Unaltered Network Activity and Interneuronal Firing During Spontaneous Cortical Dynamics In Vivo in a Mouse Model of Severe Myoclonic Epilepsy of Infancy. / De Stasi, Angela Michela; Farisello, Pasqualina; Marcon, Iacopo; Cavallari, Stefano; Forli, Angelo; Vecchia, Dania; Losi, Gabriele; Mantegazza, Massimo; Panzeri, Stefano; Carmignoto, Giorgio; Bacci, Alberto; Fellin, Tommaso.
In: CEREB CORTEX, Vol. 26, No. 4, 04.2016, p. 1778-94.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Unaltered Network Activity and Interneuronal Firing During Spontaneous Cortical Dynamics In Vivo in a Mouse Model of Severe Myoclonic Epilepsy of Infancy
AU - De Stasi, Angela Michela
AU - Farisello, Pasqualina
AU - Marcon, Iacopo
AU - Cavallari, Stefano
AU - Forli, Angelo
AU - Vecchia, Dania
AU - Losi, Gabriele
AU - Mantegazza, Massimo
AU - Panzeri, Stefano
AU - Carmignoto, Giorgio
AU - Bacci, Alberto
AU - Fellin, Tommaso
N1 - © The Author 2016. Published by Oxford University Press.
PY - 2016/4
Y1 - 2016/4
N2 - Severe myoclonic epilepsy of infancy (SMEI) is associated with loss of function of the SCN1A gene encoding the NaV1.1 sodium channel isoform. Previous studies in Scn1a(-/+) mice during the pre-epileptic period reported selective reduction in interneuron excitability and proposed this as the main pathological mechanism underlying SMEI. Yet, the functional consequences of this interneuronal dysfunction at the circuit level in vivo are unknown. Here, we investigated whether Scn1a(-/+) mice showed alterations in cortical network function. We found that various forms of spontaneous network activity were similar in Scn1a(-/+) during the pre-epileptic period compared with wild-type (WT) in vivo. Importantly, in brain slices from Scn1a(-/+) mice, the excitability of parvalbumin (PV) and somatostatin (SST) interneurons was reduced, epileptiform activity propagated more rapidly, and complex synaptic changes were observed. However, in vivo, optogenetic reduction of firing in PV or SST cells in WT mice modified ongoing network activities, and juxtasomal recordings from identified PV and SST interneurons showed unaffected interneuronal firing during spontaneous cortical dynamics in Scn1a(-/+) compared with WT. These results demonstrate that interneuronal hypoexcitability is not observed in Scn1a(-/+) mice during spontaneous activities in vivo and suggest that additional mechanisms may contribute to homeostatic rearrangements and the pathogenesis of SMEI.
AB - Severe myoclonic epilepsy of infancy (SMEI) is associated with loss of function of the SCN1A gene encoding the NaV1.1 sodium channel isoform. Previous studies in Scn1a(-/+) mice during the pre-epileptic period reported selective reduction in interneuron excitability and proposed this as the main pathological mechanism underlying SMEI. Yet, the functional consequences of this interneuronal dysfunction at the circuit level in vivo are unknown. Here, we investigated whether Scn1a(-/+) mice showed alterations in cortical network function. We found that various forms of spontaneous network activity were similar in Scn1a(-/+) during the pre-epileptic period compared with wild-type (WT) in vivo. Importantly, in brain slices from Scn1a(-/+) mice, the excitability of parvalbumin (PV) and somatostatin (SST) interneurons was reduced, epileptiform activity propagated more rapidly, and complex synaptic changes were observed. However, in vivo, optogenetic reduction of firing in PV or SST cells in WT mice modified ongoing network activities, and juxtasomal recordings from identified PV and SST interneurons showed unaffected interneuronal firing during spontaneous cortical dynamics in Scn1a(-/+) compared with WT. These results demonstrate that interneuronal hypoexcitability is not observed in Scn1a(-/+) mice during spontaneous activities in vivo and suggest that additional mechanisms may contribute to homeostatic rearrangements and the pathogenesis of SMEI.
KW - Action Potentials
KW - Animals
KW - Brain Waves
KW - Cerebral Cortex/physiopathology
KW - Disease Models, Animal
KW - Female
KW - Interneurons/metabolism
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Transgenic
KW - NAV1.1 Voltage-Gated Sodium Channel/genetics
KW - Neural Pathways/physiopathology
KW - Opsoclonus-Myoclonus Syndrome/genetics
KW - Parvalbumins/metabolism
KW - Somatostatin/metabolism
KW - Synaptic Potentials
U2 - 10.1093/cercor/bhw002
DO - 10.1093/cercor/bhw002
M3 - SCORING: Journal article
C2 - 26819275
VL - 26
SP - 1778
EP - 1794
JO - CEREB CORTEX
JF - CEREB CORTEX
SN - 1047-3211
IS - 4
ER -