Improvement of sensory deficits in Fragile X mice by increasing cortical interneuron activity after the critical period

Kourdougli, Nazim; Suresh, Anand; Liu, Benjamin; Juárez, Pablo; Lin, Andrew; Chung, David T.; Sams, Anette; Gandal, Michael J.; Martínez‐Cerdeño, Verónica; Buonomano, Dean V.; Hall, Benjamin J.; Mombereau, Cédric; Portera‐Cailliau, Carlos

doi:10.1101/2022.05.17.492368

Cited by 9 publications

(19 citation statements)

References 84 publications

(162 reference statements)

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“…For instance, it was reported that in the hippocampus, enhanced photoactivation of PV neurons elevated the proportion of PV neurons with high expression of the calcium buffer (Donato, Rompani & Caroni, 2013). More recently, Kourdougli and colleagues demonstrated that chronic (4 days) pharmacological activation of PV precursor neurons (using Nkx2.1 Cre mice) caused an increase in PV expression (Kourdougli et al, 2022). Although our work clearly demonstrates a correlation between PVp expression and the inhibitory output of these neurons, the chronological order of these events remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Parvalbumin protein controls inhibitory tone in the spinal cord

Qiu

Miraucourt

Petitjean

et al. 2022

Preprint

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The nervous system processes sensory information by relying on the precise coordination of neuronal networks and their specific synaptic firing patterns. In the spinal cord, disturbances to the firing pattern of the tonic firing parvalbumin (PV)-expressing inhibitory interneuron (PV neurons) disrupt the ability of the dorsal horn to integrate touch information and may result in pathological phenotypes. The parvalbumin protein (PVp) is a calcium (Ca2+)-binding protein that buffers the accumulation of Ca2+ following a train of action potential to allow for tonic firing. Here, we find that peripheral nerve injury causes a decrease in PVp expression in PV neurons and makes them transition from tonic to adaptive firing. We also show that reducing the expression of PVp causes otherwise healthy adult mice to develop mechanical allodynia and causes their PV neurons to lose their high frequency firing pattern. We show that this frequency adaptation is mediated by activation of SK channels on PV neurons. Further, we show their tonic firing can be partially restored after nerve injury by selectively inhibiting the SK2 channels of PV neurons. We also reveal that a decrease in the transcriptional coactivator, PGC-1α causes decrease PVp expression and the development of mechanical allodynia. By preventing the decrease in PVp expression before nerve injury, we were able to protect mice from developing mechanical allodynia. Our results indicate an essential role for PVp-mediated calcium buffering in PV neuron firing activity and the development of mechanical allodynia after nerve injury.

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Section: Discussionmentioning

confidence: 99%

Parvalbumin protein controls inhibitory tone in the spinal cord

Qiu

Miraucourt

Petitjean

et al. 2022

Preprint

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“…We previously reported avoidance and defensive gestures to repetitive whisker stimulation in Fmr1 KO mice (He et al, 2017;Kourdougli et al, 2023). However, avoidance to social touch was not simply a manifestation of generalized sensory hypersensitivity (tactile defensiveness) because it occurred in the context of social touch and not voluntary object touch (Fig.…”

Section: Discussionmentioning

confidence: 92%

A Novel Head-Fixed Assay for Social Touch in Mice Uncovers Aversive Responses in Two Autism Models

Chari,

Hernandez,

Portera-Cailliau

2023

J. Neurosci.

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Social touch, an important aspect of social interaction and communication, is essential to kinship across animal species. How animals experience and respond to social touch has not been thoroughly investigated, in part due to the lack of appropriate assays. Previous studies that examined social touch in freely moving rodents lacked the necessary temporal and spatial control over individual touch interactions. We designed a novel head-fixed assay for social touch in mice, in which the experimenter has complete control to elicit highly stereotyped bouts of social touch between two animals. The user determines the number, duration, context, and type of social touch interactions, while monitoring an array of complex behavioral responses with high resolution cameras. We focused on social touch to the face because of its high translational relevance to humans. We validated this assay in two different models of autism spectrum disorder (ASD), theFmr1knockout (KO) model of Fragile X Syndrome and maternal immune activation mice. We observed higher rates of avoidance running, hyperarousal, and aversive facial expressions (AFEs) to social touch than to object touch, in both ASD models compared to controls.Fmr1KO mice showed more AFEs to mice of the same sex but whether they were stranger or familiar mice mattered less. Because this new social touch assay for head-fixed mice can be used to record neural activity during repeated bouts of social touch it could be used to uncover underlying circuit differences.Significance StatementSocial touch is important for communication in animals and humans. However, it has not been extensively studied and current assays to measure animals’ responses to social touch have limitations. We present a novel head-fixed assay to quantify how mice respond to social facial touch with another mouse. We validated this assay in autism mouse models since autistic individuals exhibit differences in social interaction and touch sensitivity. We find that mouse models of autism exhibit more avoidance, hyperarousal, and aversive facial expressions to social touch compared to controls. Thus, this novel assay can be used to investigate behavioral responses to social touch and the underlying brain mechanisms in rodent models of neurodevelopmental conditions, and to evaluate therapeutic responses in preclinical studies.

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“…This method will control for neuronal ensembles that are actually composed of mixed populations of neurons activated by specific stimuli and those triggered by cues, contexts which are also picked up by classical electrophysiology or calcium imaging methods. Some of these combined approaches have recently started, the combination of 2-photon imaging the contribution of GABAergic vs. Glutamatergic neurons in shaping ensembles in the barrel cortex (Bollmann et al, 2023;Kourdougli et al, 2023), two-photon imaging has also established a cause -and-effect link between Fos and place cell activity (Pettit et al, 2022), Fos positive neurons are a more reliable index of place places than nonpositive Fos cells. A surprising twist to the story has also come from the combined use of in vivo 2-photon and Fos imaging (Lee et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Approaches and considerations of studying neuronal ensembles: a brief review

Davidson,

Mascarin,

Yahya

et al. 2023

Front. Cell. Neurosci.

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First theorized by Hebb, neuronal ensembles have provided a framework for understanding how the mammalian brain operates, especially regarding learning and memory. Neuronal ensembles are discrete, sparsely distributed groups of neurons that become activated in response to a specific stimulus and are thought to provide an internal representation of the world. Beyond the study of region-wide or projection-wide activation, the study of ensembles offers increased specificity and resolution to identify and target specific memories or associations. Neuroscientists interested in the neurobiology of learning, memory, and motivated behavior have used electrophysiological-, calcium-, and protein-based proxies of neuronal activity in preclinical models to better understand the neurobiology of learned and motivated behaviors. Although these three approaches may be used to pursue the same general goal of studying neuronal ensembles, technical differences lead to inconsistencies in the output and interpretation of data. This mini-review highlights some of the methodologies used in electrophysiological-, calcium-, and protein-based studies of neuronal ensembles and discusses their strengths and weaknesses.

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Improvement of sensory deficits in Fragile X mice by increasing cortical interneuron activity after the critical period

Cited by 9 publications

References 84 publications

Parvalbumin protein controls inhibitory tone in the spinal cord

Parvalbumin protein controls inhibitory tone in the spinal cord

A Novel Head-Fixed Assay for Social Touch in Mice Uncovers Aversive Responses in Two Autism Models

Approaches and considerations of studying neuronal ensembles: a brief review

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