Unspooling the Thread: VIP Interneurons Linked With Autism Spectrum Disorder Behaviors but Not Seizures in Dravet Syndrome DOI Open Access
Raquel M. Miralles, Manoj K. Patel

Epiliepsy currents/Epilepsy currents, Journal Year: 2023, Volume and Issue: 24(1), P. 62 - 64

Published: Dec. 27, 2023

[Box: see text]

Language: Английский

Postnatal development of vasoactive intestinal polypeptide‐expressing GABAergic interneurons in mouse somatosensory cortex DOI Creative Commons

Clara A. Simacek,

Sergei Kirischuk, Thomas Mittmann

et al.

Acta Physiologica, Journal Year: 2025, Volume and Issue: 241(2)

Published: Jan. 13, 2025

Despite dysfunctional vasoactive intestinal polypeptide-positive interneurons (VIP-INs) being linked to the emergence of neurodevelopmental disorders, temporal profile VIP-IN functional maturation and cortical network integration remains unclear. Postnatal development was traced with patch clamp experiments in somatosensory cortex Vip-IRES-cre x tdTomato mice. Age groups were chosen during barrel field formation, before after activation main sensory inputs, adult animals (postnatal days (P) P3-4, P8-10, P14-16, P30-36). Changes passive active membrane properties show a towards accelerated signal integrations. Excitatory inhibitory postsynaptic currents (EPSCs IPSCs) showed progressive into networks, likely via synaptogenesis: mEPSC frequency increased while mIPSC at P14-16. Only kinetics became accelerated, E/I ratio synaptic defined as charge transfer, remained constant throughout investigated developmental stages. Evoked (e)EPSCs (e)IPSCs amplitudes, only eIPSCs demonstrated faster kinetics. eEPSCs revealed paired-pulse facilitation by indicating probably decrease presynaptic release probability (pr) depression adulthood. also latter, suggesting pr for both transmission pathways this time point. VIP-INs mature pursue different strategies avoid overexcitation. become stronger shorter pre- alterations, promoting execution whisking.

Language: Английский

Citations

1
Ndnf interneuron excitability is spared in a mouse model of Dravet syndrome DOI
Sophie R Liebergall, Ethan M. Goldberg

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: unknown, P. e1977232024 - e1977232024

Published: March 5, 2024

Dravet syndrome (DS) is a neurodevelopmental disorder characterized by epilepsy, developmental delay/intellectual disability, and features of autism spectrum disorder, caused heterozygous loss-of-function variants in SCN1A encoding the voltage-gated sodium channel α subunit Nav1.1. The dominant model DS pathogenesis “interneuron hypothesis,” whereby GABAergic interneurons (INs) express preferentially rely on Nav1.1-containing channels for action potential generation. This has been shown three major subclasses cerebral cortex INs: those expressing parvalbumin, somatostatin, vasoactive intestinal peptide. Here, we define function fourth subclass INs Neuron-derived neurotrophic factor (Ndnf) male female ( Scn1a +/-) mice. Patch clamp electrophysiological recordings Ndnf-INs brain slices from +/- mice wild-type controls reveal normal intrinsic membrane properties, properties generation repetitive firing, synaptic transmission across development. Immunohistochemistry shows that Nav1.1 strongly expressed at axon initial segment (AIS) parvalbumin but absent Ndnf-IN AIS. In vivo two-photon calcium imaging demonstrates Scn1a+/- are recruited similarly to during arousal. These results suggest only IN does not prominently generation, thus retain their excitability DS. Discovery with preserved mouse adds further complexity hypothesis” highlights importance considering cell type heterogeneity when investigating mechanisms underlying disorders. Significance Statement severe impairment, due mutations gene Prior work demonstrated impaired spike subtypes inhibitory models prominent expression vs. excitatory principal cells. show previously unexamined interneuron subtype – neocortical layer 1 neuron-derived unique among they do exhibit electrical syndrome. complex cellular circuit this disorder.

Language: Английский

Citations

8
Medial prefrontal cortex circuitry and social behaviour in autism DOI

Diego H. Mediane,

Shinjini Basu, Emma Cahill

et al.

Neuropharmacology, Journal Year: 2024, Volume and Issue: 260, P. 110101 - 110101

Published: Aug. 14, 2024

Language: Английский

Citations

5
Inhibitory and disinhibitory VIP IN-mediated circuits in neocortex DOI Creative Commons

Shlomo S. Dellal,

Hector Zurita, Manuel Valero

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Cortical GABAergic interneurons (INs) are comprised of distinct types that provide tailored inhibition to pyramidal cells (PCs) and other INs, thereby enabling precise control cortical circuit activity. INs expressing the neuropeptide vasoactive-intestinal peptide (VIP) have attracted attention recently following discovery they predominantly function by inhibiting dendritic-targeting somatostatin (SST) disinhibiting PCs. This VIP-SST disinhibitory motif is observed throughout neocortex from mice humans, serves as a key mechanism for top-down (feedback) context-dependent information processing. Thus, VIP IN-mediated disinhibition has been found play an important role in sensory processing, executive functions, attention, sensorimotor integration cortico-cortical thalamocortical feedback interactions. Furthermore, implicated mediating effects reinforcement signals, both reward aversive, via their responsiveness neuromodulators such acetylcholine (ACh), facilitating synaptic plasticity learning. While it evident transcriptomic analyses molecularly heterogeneous group, physiological significance this diversity unclear at present. Here, we characterized functional primary somatosensory cortex leveraging intersectional genetic approaches study IN subtypes. We can be divided into four different populations: group expresses Ca 2+ -binding protein calretinin (CR), two groups express cholecystokinin (CCK), does not either CR or CCK (non-CCK non-CR; nCCK nCR). neurons each exhibit laminar distributions, axonal dendritic arbors, intrinsic electrophysiological properties, efferent connectivity, VIP/CR target almost exclusively SST VIP/nCCK nCR also mainly but connections parvalbumin (PV) INs. These essentially no connectivity (PCs). On hand, VIP/CCK PCs, differ degree which release type modulated endocannabinoids. long-range inputs differentially recruit groups. Intriguingly, find populations subtypes turn, indicating presence specialized subcircuits. Activation subpopulations vivo results differential on network, thus providing evidence modularity actions during

Language: Английский

Citations

0
Genetic Diagnostic Yield in Autism Spectrum Disorder (ASD) and Epilepsy Phenotypes in Children with Genetically Defined ASD DOI
Karen Lob, Danielle M. Sawka, John Gaitanis

et al.

Journal of Autism and Developmental Disorders, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 13, 2024

Language: Английский

Citations

3
Interneuronal modulations as a functional switch for cortical computations: mechanisms and implication for disease DOI Creative Commons
Yann Zerlaut, Alexandra Tzilivaki

Frontiers in Cellular Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: Jan. 23, 2025

Understanding cortical inhibition and its diverse roles remains a key challenge in neurophysiological research. Traditionally, has been recognized for controlling the stability rhythmicity of network dynamics, or refining spatiotemporal properties representations. In this perspective, we propose that specific types interneurons may play complementary role, by modulating computational neural networks. We review experimental theoretical evidence, mainly from rodent sensory cortices, supports view. Additionally, explore how dysfunctions these disrupt network’s ability to switch between modes, impacting flexibility processing potentially contributing various neurodevelopmental psychiatric disorders.

Language: Английский

Citations

0
Inhibition of BK channels by GABAb receptors enhances intrinsic excitability of layer 2/3 vasoactive intestinal polypeptide‐expressing interneurons in mouse neocortex DOI Creative Commons
Karolina Bogaj, Joanna Urban-Ciećko

The Journal of Physiology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Abstract GABAb receptors (GABAbRs) affect many signalling pathways, and hence the net effect of activity these depends upon specific ion channels that they are linked to, leading to different effects on neuronal populations. Typically, GABAbRs suppress in cerebral cortex. Previously, we found neocortical parvalbumin‐expressing cells strongly inhibited through GABAbRs, whereas somatostatin interneurons immune this modulation. Here, employed vitro whole‐cell patch‐clamp recordings study whether modulate vasoactive intestinal polypeptide‐expressing (VIP‐INs) layer (L) 2/3 mouse primary somatosensory Utilizing machine learning algorithms (hierarchical clustering principal component analysis), revealed one VIP‐IN cluster (about 68% all VIP‐INs) was sensitive GABAbR activation. Paradoxically, when were performed standard conditions with high extracellular Ca 2+ level, indirectly large conductance voltage‐ calcium‐activated potassium (BK) reduced GABAaR‐mediated inhibition, an increase intrinsic excitability interneurons. However, a classical inhibitory L2/3 VIP‐INs observed modified artificial cerebrospinal fluid physiological (low) concentration. Our results essential for deeper understanding mechanisms underlying modulation cortical networks. image Key points Layer cortex into three electrophysiological types differentially (GABAbRs). The majority (type 1, about regulated pre‐ postsynaptic while subset (types 2 3) is controlled only presynaptically. activation [Ca ] fluid. When (2.5 mM), inhibit BK reduce GABAaR inhibition increased type 1 VIP‐INs. low (1 which more physiological, do not regulate thus canonically decrease

Language: Английский

Citations

0
Dynamic regulation of cortical interneuron wiring DOI Creative Commons

Claudia Rosés-Novella,

C. Bernard

Current Opinion in Neurobiology, Journal Year: 2025, Volume and Issue: 92, P. 102980 - 102980

Published: Feb. 26, 2025

Language: Английский

Citations

0
Prenatal Valproic Acid Exposure Impairs Offspring Cognition Through Disturbing Interneuron Development DOI Creative Commons

Kaiyuan Shen,

Yandong Zhang, Yunyun Huang

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(2)

Published: Feb. 1, 2025

Valproic acid (VPA) exposure during the gestational period has been found to impair cognition of offspring. The study aimed investigate whether VPA leads offspring cognitive impairment through disturbing interneuron development. Pregnant mice were injected with peritoneally establish prenatal model. Cortical interneurons labeled Rosa26-EYFP/- reporter activated by Nkx2.1-Cre. Interneuron subtypes both in cortex and hippocampus detected immunofluorescence. A battery behavioral tests was conducted on postnatal Day 28 assess anxiety RNA-Seq analysis performed underlying molecular mechanisms. We that after VPA, all groups male exerted anxiety. When injection 12.5, memory impaired. Mechanistically, distribution cortical disrupted. abnormal exposure, which affected somatostatin-positive neurons but not parvalbumin-positive neurons, indicating effects subtype specific. Biological processes related ion homeostasis greatly changed exposure. Prenatal neurogenic impaired disrupting migration differentiation. provides a novel perspective influence over neurodevelopment.

Language: Английский

Citations

0
Disorganized Inhibitory Dynamics and Functional Connectivity in Hippocampal area CA1 of 22q11.2 Deletion Mutant Mice DOI Creative Commons
Stephanie Herrlinger, Bovey Rao,

Margaret E. Conde Paredes

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 30, 2024

Individuals with the 22q11.2 deletion syndrome, one of strongest genetic risk factors for schizophrenia, demonstrate cognitive impairments including episodic memory dysfunction. Place cell activity excitatory pyramidal neurons in hippocampus supporting are impaired a mouse model ( Df(16)A +/- ). While dynamics under tight inhibitory control by multiple subtypes GABAergic interneurons, previous studies have predominantly focused on single subtype PV-expressing interneurons; there not yet been describing functional relationships between molecularly identified types mice. Here, we examined interneuron subtype-specific dorsal hippocampal area CA1 mice during random foraging and spatial reward learning tasks. Capitalizing 3D acousto-optical deflector two-photon microscopy post hoc immunohistochemical identification, found that exhibit aberrant responses to locations delayed enrichment extinction. interneurons also carry markedly reduced information subtype-dependent manner. We observed task-dependent changes correlation structure coactivity among subtypes, suggesting broadly disorganized microcircuit functionality mutant Overall, identify widespread heterogeneous alterations learning, reflecting flexibility organization microcircuits. Our study provides critical insights into how schizophrenia-risk mutations affect local-circuit interactions diverse navigation.

Language: Английский

Citations

2