Lineage reprogramming of glial cells into induced neurons (iNs) has emerged as an innovative strategy to replace neurons lost due to injury or neurological diseases. Here, we describe a step-by-step protocol to induce in vivo conversion of reactive glial cells, proliferating within the injured hippocampus, into mature and functional GABAergic iNs through retrovirus-mediated expression of two neurogenic fate determinants (Ascl1 and Dlx2). We have previously applied this method to study the integration and functional impact of GABAergic iNs in epileptic mice (Lentini et al., Cell Stem Cell 28:2104-2121.e10, 2021). We successfully generated GABAergic iNs that exhibited substantial integration within pathological circuits, leading to a significant reduction in epileptic seizures.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/978-1-0716-4386-0_14 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Retrovirus-Mediated Reprogramming of Endogenous Hippocampal Glia into GABAergic Induced Neurons.
Methods Mol Biol
March 2025
Univ Lyon, Université Claude Bernard Lyon 1, INSERM, Stem Cell and Brain Research Institute U1208, Bron, France.
Lineage reprogramming of glial cells into induced neurons (iNs) has emerged as an innovative strategy to replace neurons lost due to injury or neurological diseases. Here, we describe a step-by-step protocol to induce in vivo conversion of reactive glial cells, proliferating within the injured hippocampus, into mature and functional GABAergic iNs through retrovirus-mediated expression of two neurogenic fate determinants (Ascl1 and Dlx2). We have previously applied this method to study the integration and functional impact of GABAergic iNs in epileptic mice (Lentini et al.
View Article and Find Full Text PDFCortical GABAergic interneurons (INs) are comprised of distinct types that provide tailored inhibition to pyramidal cells (PCs) and other INs, thereby enabling precise control of cortical circuit activity. INs expressing the neuropeptide vasoactive-intestinal peptide (VIP) have attracted attention recently following the discovery that they predominantly function by inhibiting dendritic-targeting somatostatin (SST) expressing INs, thereby disinhibiting PCs. This VIP-SST disinhibitory circuit motif is observed throughout the neocortex from mice to humans, and serves as a key mechanism for top-down (feedback) and context-dependent information processing.
View Article and Find Full Text PDFHeterogeneity of Layer 1 Interneurons in the Mouse Medial Prefrontal Cortex.
J Comp Neurol
March 2025
Department of Neurosciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
Cortical Layer 1 (L1) acts as a critical relay for processing long-range inputs. GABAergic inhibitory interneurons (INs) in this layer (Layer 1 interneurons [L1INs]) function as inhibitory gates, regulating these inputs and modulating the activity of deeper cortical layers. However, their characteristics and circuits in the medial prefrontal cortex (mPFC) remain poorly understood.
View Article and Find Full Text PDFThe proper functioning of the central nervous system depends on the cooperation of distinct neuronal subtypes generated during development. Here, we review new insights provided by recent research and technological advances into the mechanisms underlying the generation of the remarkable diversity of inhibitory GABAergic neurons (INs). INs are generated in the ventral telencephalon or subpallium and migrate long distances to populate multiple brain regions.
View Article and Find Full Text PDFMotor cortex stimulation ameliorates parkinsonian locomotor deficits: effectual and mechanistic differences from subthalamic modulation.
NPJ Parkinsons Dis
February 2025
Department of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.
Subthalamic deep brain stimulation (STN DBS) has been a therapeutic choice for Parkinson's disease (PD). We found that epidural motor cortex stimulation (MCS) with sustained positive (hyperpolarizing) currents could also consistently ameliorate the locomotor deficits in parkinsonian animals, rectifying the pathological paucity in both discharging unit varieties and movement-dependent spatiotemporal activity pattern changes in motor cortex (MC). Mechanistically, MCS hyperpolarizes both glutamatergic pyramidal neurons (PN) and GABAergic interneurons (IN) and consequently partly relieves PN from IN's control.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!