Single-cell profiling of cortical tubers in tuberous sclerosis complex shows molecular structure preservation and massive reorganization of metabolism DOI Creative Commons
Frederik N. F. Sørensen, Tin Luka Petanjek,

Mirte Scheper

et al.

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

Published: Oct. 31, 2024

Abstract Tuberous sclerosis complex (TSC) is a multisystemic genetic disorder associated with loss-of-function mutations in the TSC1 or TSC2 gene, which lead mTOR pathway hyperactivation and epileptogenesis. Cortical tubers are hallmark of TSC represent disorganized cortical structure underlying generation focal seizures. Here, we report single-nucleus RNA sequencing resected vs matched pediatric controls. Strikingly, spite severe disorganization, found that preserve all neuronal subtypes, even rarest ones. Moreover, showed principal neurons largely spatial position based on transcriptional signatures. Principal layer 1-2 GABAergic modulate upper circuits exhibited largest gene expression changes. Interestingly, multiple changes counteracted hyperactivation. neuronal, but not glial, networks massive metabolic reorganization reduction mitochondrial respiration concomitant switch to fatty acid metabolism. Finally, show neuron-specific AMPA receptor signaling might underlie epileptogenesis could potential candidate for therapeutic targeting.

Language: Английский

Layer 1 NDNF interneurons form distinct subpopulations with opposite activation patterns during sleep in freely behaving mice DOI Creative Commons
Aurélie Brécier,

Mailhos Gaëlle,

Przemysław Jarzębowski

et al.

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

Published: Jan. 11, 2025

ABSTRACT Non-rapid eye movement (NREM) sleep facilitates memory consolidation by transferring information from the hippocampus to neocortex. Recent evidence suggests that this transfer occurs primarily when hippocampal sharp-wave ripples (SWRs) and thalamocortical spindles are synchronized. In study, we asked what role cortical layer 1 NDNF-expressing (L1 NDNF) interneurons play during NREM in gating SWR-spindle synchronization. Using simultaneous cell-specific calcium imaging local field potential recordings freely moving mice, discovered L1 NDNF neurons form cell assemblies tuned specific stages, exhibiting differential responses spindle mediate slow inhibition through GABA B receptors. Systemic application of a receptor antagonist increased pyramidal neuron excitability sleep, enhanced inhibitory SWRs, disrupted coupling. Overall, these findings suggest an important contribution neuron-mediated synchronization oscillations with implications for processes.

Language: Английский

Citations

0
Layer-specific control of inhibition by NDNF interneurons DOI
Laura Naumann, Loreen Hertäg, Jennifer Müller

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(4)

Published: Jan. 22, 2025

Neuronal processing of external sensory input is shaped by internally generated top–down information. In the neocortex, projections primarily target layer 1, which contains NDNF (neuron-derived neurotrophic factor)-expressing interneurons and dendrites pyramidal cells. Here, we investigate hypothesis that shape cortical computations in an unconventional, layer-specific way, exerting presynaptic inhibition on synapses 1 while leaving deeper layers unaffected. We first confirm experimentally auditory cortex, from somatostatin-expressing (SOM) onto neurons are indeed modulated ambient Gamma-aminobutyric acid (GABA). Shifting to a computational model, then show this mechanism introduces distinct mutual motif between synaptic outputs SOM interneurons. This can control way competition for dendritic cells different timescales. thereby information flow redistributing fast slow timescales gating sources inhibition.

Language: Английский

Citations

0
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
Dynamic changes in cortical neurotrophic factor-positive interneurons during sleep DOI Creative Commons
Christine Muheim,

Marcos G. Frank

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 21, 2025

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
Heterogeneity of Layer 1 Interneurons in the Mouse Medial Prefrontal Cortex DOI Creative Commons
Chen Shen,

Wanpeng Cui,

Wen‐Cheng Xiong

et al.

The Journal of Comparative Neurology, Journal Year: 2025, Volume and Issue: 533(3)

Published: March 1, 2025

Cortical Layer 1 (L1) acts as a critical relay for processing long-range inputs. GABAergic inhibitory interneurons (INs) in this layer (Layer [L1INs]) function gates, regulating these inputs and modulating the activity of deeper cortical layers. However, their characteristics circuits medial prefrontal cortex (mPFC) remain poorly understood. Using biocytin labeling, we identified three distinct morphological types mPFC L1INs: neurogliaform cells (NGCs), elongated NGCs (eNGCs), single-bouquet cell-like (SBC-like) cells. Whole-cell recordings revealed firing patterns across subtypes: eNGCs predominantly exhibited late-spiking (LS) patterns, SBC-like displayed higher prevalence non-LS (NLS) patterns. We observed both electrical chemical connections among L1INs. Optogenetic activation NDNF+ L1INs demonstrated broad effects on neurons. The strength inhibition pyramidal neurons (PyNs) INs layer-specific preference. These findings highlight functional diversity suggest potential role supporting order cognitive functions.

Language: Английский

Citations

0
Reliable sensory processing of superficial cortical interneurons is modulated by behavioral state DOI Creative Commons
Carolyn G. Sweeney, Maryse E. Thomas, Christine Liu

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(5), P. 115678 - 115678

Published: May 1, 2025

Language: Английский

Citations

0
Neurogliaform Cells Exhibit Laminar-specific Responses in the Visual Cortex and Modulate Behavioral State-dependent Cortical Activity DOI Creative Commons
Shuhan Huang,

Daniella Rizzo,

Jingjing Sherry Wu

et al.

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

Published: June 8, 2024

Neurogliaform cells are a distinct type of GABAergic cortical interneurons known for their volume transmission output property. However, activity and function within circuits remain unclear. Here, we developed two genetic tools to target these neurons examine in the primary visual cortex. We found that spontaneous neurogliaform positively correlated with locomotion. Silencing increased during locomotion impaired responses L2/3 pyramidal neurons. Furthermore, contrast-dependent response varies laminar location is constrained by morphology input connectivity. These findings demonstrate importance regulating behavioral state-dependent indicate functional engagement stimuli influenced positioning

Language: Английский

Citations

1
Genetic approaches to elucidating cortical and hippocampal GABAergic interneuron diversity DOI Creative Commons
Robert Machold, Bernardo Rudy

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: July 24, 2024

GABAergic interneurons (INs) in the mammalian forebrain represent a diverse population of cells that provide specialized forms local inhibition to regulate neural circuit activity. Over last few decades, development palette genetic tools along with generation single-cell transcriptomic data has begun reveal molecular basis IN diversity, thereby providing deep insights into how different subtypes function forebrain. In this review, we outline emerging picture cortical and hippocampal speciation as defined by transcriptomics developmental origin summarize strategies have been utilized target specific subtypes, technical considerations inherent each approach. Collectively, these methods greatly facilitated our understanding circuitry via cell type compartment-specific thus illuminated path toward potential therapeutic interventions for variety neurocognitive disorders.

Language: Английский

Citations

1
Neurogliaform Cells Exhibit Laminar-specific Responses in the Visual Cortex and Modulate Behavioral State-dependent Cortical Activity DOI Creative Commons
Gord Fishell, Shuhan Huang,

Daniella Rizzo

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: July 2, 2024

Abstract Neurogliaform cells are a distinct type of GABAergic cortical interneurons known for their ‘volume transmission’ output property. However, activity and function within circuits remain unclear. Here, we developed two genetic tools to target these neurons examine in the primary visual cortex. We found that spontaneous neurogliaform positively correlated with locomotion. Silencing increased during locomotion impaired responses L2/3 pyramidal neurons. Furthermore, contrast-dependent response varies laminar location is constrained by morphology input connectivity. These findings demonstrate importance regulating behavioral state-dependent indicate functional engagement stimuli influenced positioning

Language: Английский

Citations

0