ArticleMolecular autism2020
Tsc1 haploinsufficiency in Nkx2.1 cells upregulates hippocampal interneuron mTORC1 activity, impairs pyramidal cell synaptic inhibition, and alters contextual fear discrimination and spatial working memory in mice.
Article in Molecular autism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Tuberous sclerosis complex.Nature reviews. Disease primers · 2026Review
- Conditional learning increases inhibition of layer 4 excitatory neurons by somatostatin- and parvalbumin-expressing interneurons in the barrel cortex.Journal of neural transmission (Vienna, Austria : 1996) · 2025Article
- Somatic mosaicism and interneuron involvement in mTORopathies.Trends in neurosciences · 2025Review
- Developmental and molecular contributions to contextual fear memory emergence in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Rodent Models for ASD Biomarker Development.Advances in neurobiology · 2024Review
- Insights into the structure and function of the hippocampus: implications for the pathophysiology and treatment of autism spectrum disorder.Frontiers in psychiatry · 2024Review
- Article
- Ocular and neural genes jointly regulate the visuospatial working memory in ADHD children.Behavioral and brain functions : BBF · 2023Article
- Role of Type I Interferon Signaling and Microglia in the Abnormal Long-term Potentiation and Object Place Recognition Deficits of Male Mice With a Mutation of the Tuberous Sclerosis 2 Gene.Biological psychiatry global open science · 2023Article
- Maturation of nucleus accumbens synaptic transmission signals a critical period for the rescue of social deficits in a mouse model of autism spectrum disorder.Molecular brain · 2023Article
- Critical periods and Autism Spectrum Disorders, a role for sleep.Neurobiology of sleep and circadian rhythms · 2023Article
- Cellular signaling impacts upon GABAergic cortical interneuron development.Frontiers in neuroscience · 2023Review
- Embryonic Arsenic Exposure Triggers Long-Term Behavioral Impairment with Metabolite Alterations in Zebrafish.Toxics · 2022Article
- Article
- Bumetanide Effects on Resting-State EEG in Tuberous Sclerosis Complex in Relation to Clinical Outcome: An Open-Label Study.Frontiers in neuroscience · 2022Article
- Reversing frontal disinhibition rescues behavioural deficits in models of CACNA1A-associated neurodevelopment disorders.Molecular psychiatry · 2021Article
- Understanding autism spectrum disorders with animal models: applications, insights, and perspectives.Zoological research · 2021Review
- Development, Diversity, and Death of MGE-Derived Cortical Interneurons.International journal of molecular sciences · 2021Review
- Effects of Mutations in TSC Genes on Neurodevelopment and Synaptic Transmission.International journal of molecular sciences · 2021Review
- Sensitive period for rescuing parvalbumin interneurons connectivity and social behavior deficits caused by TSC1 loss.Nature communications · 2021Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMutations in TSC1 or TSC2 genes cause tuberous sclerosis complex (TSC), a disorder associated with epilepsy, autism, and intellectual disability. TSC1 and TSC2 are repressors of the mechanistic target of rapamycin complex 1 (mTORC1), a key regulator of protein synthesis. Dysregulation of mTORC1 in TSC mouse models leads to impairments in excitation-inhibition balance, synaptic plasticity, and hippocampus-dependent learning and memory deficits. However, synaptic inhibition arises from multiple types of inhibitory interneurons and how changes in specific interneurons contribute to TSC remains largely unknown. In the present work, we determined the effect of conditional Tsc1 haploinsufficiency in a specific subgroup of inhibitory cells on hippocampal function in mice.
methodsWe investigated the consequences of conditional heterozygous knockout of Tsc1 in MGE-derived inhibitory cells by crossing Nkx2.1
resultsWe detected selective increases in phosphorylation of ribosomal protein S6 in interneurons, indicating cell-specific-upregulated mTORC1 signaling. At the behavioral level, Nkx2.1
conclusionsOur results indicate that Tsc1 haploinsufficiency in MGE-derived inhibitory cells upregulates mTORC1 activity in these interneurons, reduces their synaptic inhibition of pyramidal cells, and alters contextual fear discrimination and spatial working memory. Thus, selective dysregulation of mTORC1 function in Nkx2.1-expressing inhibitory cells appears sufficient to impair synaptic inhibition and contributes to cognitive deficits in the Tsc1 mouse model of TSC.
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