IRSp53 Deletion in Glutamatergic and GABAergic Neurons and in Male and Female Mice Leads to Distinct Electrophysiological and Behavioral Phenotypes

Kim, Yangsik; Noh, Young Woo; Kim, Kyungdeok; Yang, Esther; Kim, Hyun; Kim, Eunjoon

doi:10.3389/fncel.2020.00023

Cited by 15 publications

(33 citation statements)

References 68 publications

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“…Here, we provide an in vivo example of this concept by demonstrating that IRSp53-KO mPFC excitatory neurons show increased spontaneous firing activity but a limited firing-rate range during social and non-social cue exploration. The heightened firing rates of mPFC pExc neurons in IRSp53-KO mice during the rest period may be attributable to the increased intrinsic excitability of pyramidal mPFC neurons, as reported in IRSp53-KO mice with gene deletion restricted to excitatory neurons (Kim et al, 2020). An elevated firing rate at rest was observed for mPFC neurons in socially impaired Cntnap2-KO mice; this was .…”

Section: Discussionmentioning

confidence: 65%

“…The heightened firing rates of mPFC pExc neurons in IRSp53-KO mice during the rest period may be attributable to the increased intrinsic excitability of pyramidal mPFC neurons, as reported in IRSp53-KO mice with gene deletion restricted to excitatory neurons (Kim et al, 2020). An elevated firing rate at rest was observed for mPFC neurons in socially impaired Cntnap2-KO mice; this was is the firing rate at the target zones.…”

Section: Discussionmentioning

confidence: 65%

“…IRSp53 deficiency in mice leads to excitatory synaptic deficits and various behavioral deficits, including hyperactivity, cognitive impairments, and social deficits (Bobsin and Kreienkamp, 2016;Chung et al, 2015;Kim et al, 2009;Kim et al, 2020;Sawallisch et al, 2009). IRSp53 knockout (KO) mice have fewer dendritic spines and enhanced NMDA receptor (NMDAR) function; they show impaired social behavior that is rescued by pharmacological NMDAR suppression (Chung et al, 2015;Kim et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

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Suppressed prefrontal neuronal firing variability and impaired social representation in IRSp53-mutant mice

Kim

Noh

Lee

et al. 2021

Preprint

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Social deficit is a major feature of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, and attention-deficit/hyperactivity disorder, but its neural mechanisms remain unclear. Here, we examined neuronal discharge characteristics in the medial prefrontal cortex (mPFC) of IRSp53-mutant mice, which show social deficits, during social approach. IRSp53-mutant excitatory mPFC neurons displayed an increase in baseline neuronal firing and decreases in variability and dynamic range of firing rates and burst firing during social and non-social target approaches compared to wild-type controls. As a consequence, their firing activity was less differential between social and non-social targets. In addition, there was a decrease in the proportion of excitatory mPFC neurons encoding social information but not that of those encoding non-social information. These results suggest that insufficient neuronal activity dynamics may underlie impaired cortical encoding of social information and social behaviors in IRSp53-mutant mice.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 65%

Section: Introductionmentioning

confidence: 99%

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Suppressed prefrontal neuronal firing variability and impaired social representation in IRSp53-mutant mice

Kim

Noh

Lee

et al. 2021

Preprint

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“…Studies have shown that IRSp53 is involved in various brain disorders, including ASD [98,99], attention deficit hyperactivity disorder [100] and schizophrenia [101]. A deletion of Irsp53 leads to sexdependent changes in behaviour, such as social deficit, hyperreactivity and excitatory/inhibitory imbalance [102]. A lack of IRSp53 activity leads to NMDA receptor hyperreactivity in the hippocampus [103] and prepulse inhibition in cortical excitatory neurons [102].…”

Section: Shank Family Of Genesmentioning

confidence: 99%

The role of selected postsynaptic scaffolding proteins at glutamatergic synapses in autism-related animal models

Meliskova¹,

Havránek²,

Bačová³

et al. 2021

Journal of Integrative Neuroscience

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Pathological changes in synapse formation, plasticity and development are caused by altered trafficking and assembly of postsynaptic scaffolding proteins at sites of glutamatergic and gammaaminobutyric acid synapses, suggesting their involvement in the etiology of neurodevelopmental disorders, including autism. Several autism-related mouse models have been developed in recent years for studying molecular, cellular and behavioural defects to understand the etiology of autism and test potential treatment strategies. In this review, the role of alterations in selected postsynaptic scaffolding proteins in relevant transgene autism-like mouse models is explained. A summary is also provided of selected animal models by paying special attention to interactions between guanylate kinases or membrane-associated guanylate kinases, as well as other synapse protein components which form functional synaptic networks. The study of early developmental stages of autism-relevant animal models help in the understanding the origin and development of diverse autistic symptomatology.

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“…In contrast, in the medial prefrontal cortex (mPFC), IRSp53 −/− mice show a decrease in frequency and amplitude of mEPSCs and synapse numbers by EM without affecting NMDA receptor function (Chung et al, 2015 ). Deletion of IRSp53 in glutamatergic neurons and GABAergic mPFC neurons lead to distinct behavioral deficits and synaptic changes between male and female mice (Kim et al, 2020 ). Whether these differences reflect alterations at the synaptic or circuit level or reflect compensation by other I-BAR proteins is not yet clear.…”

Section: Introductionmentioning

confidence: 99%

Revisiting I-BAR Proteins at Central Synapses

Chatzi

Westbrook

2021

Front. Neural Circuits

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Dendritic spines, the distinctive postsynaptic feature of central nervous system (CNS) excitatory synapses, have been studied extensively as electrical and chemical compartments, as well as scaffolds for receptor cycling and positioning of signaling molecules. The dynamics of the shape, number, and molecular composition of spines, and how they are regulated by neural activity, are critically important in synaptic efficacy, synaptic plasticity, and ultimately learning and memory. Dendritic spines originate as outward protrusions of the cell membrane, but this aspect of spine formation and stabilization has not been a major focus of investigation compared to studies of membrane protrusions in non-neuronal cells. We review here one family of proteins involved in membrane curvature at synapses, the BAR (Bin-Amphiphysin-Rvs) domain proteins. The subfamily of inverse BAR (I-BAR) proteins sense and introduce outward membrane curvature, and serve as bridges between the cell membrane and the cytoskeleton. We focus on three I-BAR domain proteins that are expressed in the central nervous system: Mtss2, MIM, and IRSp53 that promote negative, concave curvature based on their ability to self-associate. Recent studies suggest that each has distinct functions in synapse formation and synaptic plasticity. The action of I-BARs is also shaped by crosstalk with other signaling components, forming signaling platforms that can function in a circuit-dependent manner. We discuss another potentially important feature—the ability of some BAR domain proteins to impact the function of other family members by heterooligomerization. Understanding the spatiotemporal resolution of synaptic I-BAR protein expression and their interactions should provide insights into the interplay between activity-dependent neural plasticity and network rewiring in the CNS.

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IRSp53 Deletion in Glutamatergic and GABAergic Neurons and in Male and Female Mice Leads to Distinct Electrophysiological and Behavioral Phenotypes

Cited by 15 publications

References 68 publications

Suppressed prefrontal neuronal firing variability and impaired social representation in IRSp53-mutant mice

Suppressed prefrontal neuronal firing variability and impaired social representation in IRSp53-mutant mice

The role of selected postsynaptic scaffolding proteins at glutamatergic synapses in autism-related animal models

Revisiting I-BAR Proteins at Central Synapses

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