CaV2.1 ablation in cortical interneurons selectively impairs fast-spiking basket cells and causes generalized seizures
Elsa Rossignol,Elsa Rossignol,Illya Kruglikov,Arn M. J. M. van den Maagdenberg,Bernardo Rudy,Gord Fishell +5 more
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TLDR
In this paper, the α1 pore-forming subunit of CaV2.1 (P/Q-type) voltage-gated Ca2+ channels has been suggested to cause generalized spike-wave absence seizures.Abstract:
Background
Both the neuronal populations and mechanisms responsible for generalized spike-wave absence seizures are poorly understood. In mutant mice carrying loss-of-function mutations in Cacna1a, which encodes the α1 pore-forming subunit of CaV2.1 (P/Q-type) voltage-gated Ca2+ channels, generalized spike-wave seizures have been suggested to result from excessive bursting of thalamocortical cells. However, other cellular populations including cortical inhibitory interneurons may contribute to this phenotype.read more
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GABAergic Interneurons in the Neocortex: From Cellular Properties to Circuits
TL;DR: Current understanding of neocortical interneuron diversity and the properties that distinguish cell types are reviewed and it is illustrated how recent advances in the field have shed light onto the mechanisms by which GABAergic inhibition contributes to network operations.
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Fast-spiking, parvalbumin+ GABAergic interneurons: From cellular design to microcircuit function
Hua Hu,Jian Gan,Peter Jonas +2 more
TL;DR: Not only are PV+ interneurons involved in basic microcircuit functions, but they also play a role in complex network operations, including expansion of dynamic activity range, pattern separation, modulation of place and grid field shapes, phase precession, and gain modulation of sensory responses.
Journal ArticleDOI
Microcircuits and their interactions in epilepsy: Is the focus out of focus?
Jeanne T. Paz,John R. Huguenard +1 more
TL;DR: Various microcircuit motifs are described, with a special emphasis on one that has been broadly implicated in several epilepsies: feed-forward inhibition, and how, in the dynamic network in which seizures propagate, focusing on circuit 'choke points' remote from the initiation site might be as important as that of the initial dysfunction, the seizure 'focus'.
Journal ArticleDOI
Impaired excitability of somatostatin- and parvalbumin-expressing cortical interneurons in a mouse model of Dravet syndrome.
TL;DR: It is shown that two major types of inhibitory neurons are impaired in generation of electrical signals by a DS mutation, whereas excitatory neurons are unaffected, and two major subtypes of interneurons in layer V of the neocortex, parvalbumin-expressing and somatostatin- expressing, both have impaired excitability, resulting in disinhibition of the cortical network.
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The interneuron energy hypothesis: Implications for brain disease
TL;DR: Fast-spiking, inhibitory interneurons - prototype is the parvalbumin-positive (PV+) basket cell - generate action potentials at high frequency and synchronize the activity of numerous excitatory principal neurons, such as pyramidal cells, during fast network oscillations by rhythmic inhibition.
References
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Driving fast-spiking cells induces gamma rhythm and controls sensory responses
Jessica A. Cardin,Marie Carlén,Marie Carlén,Konstantinos Meletis,Konstantinos Meletis,Ulf Knoblich,Feng Zhang,Karl Deisseroth,Li-Huei Tsai,Li-Huei Tsai,Li-Huei Tsai,Christopher I. Moore +11 more
TL;DR: The timing of a sensory input relative to a gamma cycle determined the amplitude and precision of evoked responses and provided the first causal evidence that distinct network activity states can be induced in vivo by cell-type-specific activation.
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A Resource of Cre Driver Lines for Genetic Targeting of GABAergic Neurons in Cerebral Cortex
Hiroki Taniguchi,Miao He,Priscilla Wu,Sangyong Kim,Raehum Paik,Ken Sugino,Duda Kvitsani,Yu Fu,Jiangteng Lu,Ying Lin,Goichi Miyoshi,Yasuyuki Shima,Gord Fishell,Sacha B. Nelson,Z. Josh Huang +14 more
TL;DR: Using genetic engineering in mice, approximately 20 Cre and inducible CreER knockin driver lines that reliably target major classes and lineages of GABAergic neurons are generated, thereby enabling a systematic and comprehensive analysis from cell fate specification, migration, and connectivity, to their functions in network dynamics and behavior.
Journal ArticleDOI
Three groups of interneurons account for nearly 100% of neocortical GABAergic neurons
TL;DR: The universal modulation of these neurons by serotonin and acetylcholine via ionotropic receptors suggests that they might be involved in shaping cortical circuits during specific brain states andbehavioral contexts.
Journal ArticleDOI
Cortical Focus Drives Widespread Corticothalamic Networks during Spontaneous Absence Seizures in Rats
Hanneke K. M. Meeren,Hanneke K. M. Meeren,J.P. Pijn,Egidius L. J. M. Van Luijtelaar,Anton M.L. Coenen,Fernando H. Lopes da Silva,Fernando H. Lopes da Silva +6 more
TL;DR: These findings argue against the existence of one common subcortical pacemaker for the generation of generalized spike-wave discharges characteristic for absence seizures in the rat and suggest that a cortical focus is the dominant factor in initiating the paroxysmal oscillation within the corticothalamic loops.
Journal ArticleDOI
Absence epilepsy in tottering mutant mice is associated with calcium channel defects
Colin F. Fletcher,Cathleen M. Lutz,T. Norene O'Sullivan,John D. Shaughnessy,Richard Hawkes,Wayne N. Frankel,Neal G. Copeland,Nancy A. Jenkins +7 more
TL;DR: The first mutations in a mammalian central nervous system-specific voltage-sensitive calcium channel gene that is mutated in tg and tg(la) mice are defined and the first gene involved in absence epilepsy is identified.