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Neuron Oct 2023One of the most captivating questions in neuroscience revolves around the brain's ability to efficiently and durably capture and store information. It must process... (Review)
Review
One of the most captivating questions in neuroscience revolves around the brain's ability to efficiently and durably capture and store information. It must process continuous input from sensory organs while also encoding memories that can persist throughout a lifetime. What are the cellular-, subcellular-, and network-level mechanisms that underlie this remarkable capacity for long-term information storage? Furthermore, what contributions do distinct types of GABAergic interneurons make to this process? As the hippocampus plays a pivotal role in memory, our review focuses on three aspects: (1) delineation of hippocampal interneuron types and their connectivity, (2) interneuron plasticity, and (3) activity patterns of interneurons during memory-related rhythms, including the role of long-range interneurons and disinhibition. We explore how these three elements, together showcasing the remarkable diversity of inhibitory circuits, shape the processing of memories in the hippocampus.
Topics: Interneurons; Hippocampus
PubMed: 37467748
DOI: 10.1016/j.neuron.2023.06.016 -
Neuron Oct 2018In the cerebral cortex, GABAergic interneurons have evolved as a highly heterogeneous collection of cell types that are characterized by their unique spatial and... (Review)
Review
In the cerebral cortex, GABAergic interneurons have evolved as a highly heterogeneous collection of cell types that are characterized by their unique spatial and temporal capabilities to influence neuronal circuits. Current estimates suggest that up to 50 different types of GABAergic neurons may populate the cerebral cortex, all derived from progenitor cells in the subpallium, the ventral aspect of the embryonic telencephalon. In this review, we provide an overview of the mechanisms underlying the generation of the distinct types of interneurons and their integration in cortical circuits. Interneuron diversity seems to emerge through the implementation of cell-intrinsic genetic programs in progenitor cells, which unfold over a protracted period of time until interneurons acquire mature characteristics. The developmental trajectory of interneurons is also modulated by activity-dependent, non-cell-autonomous mechanisms that influence their ability to integrate in nascent circuits and sculpt their final distribution in the adult cerebral cortex.
Topics: Animals; Cell Differentiation; Cell Lineage; Cerebral Cortex; GABAergic Neurons; Humans; Interneurons; Neural Stem Cells; Neurogenesis
PubMed: 30359598
DOI: 10.1016/j.neuron.2018.10.009 -
The FEBS Journal Apr 2022Understanding excitation and inhibition balance in the brain begins with the tale of two basic types of neurons, glutamatergic projection neurons and GABAergic... (Review)
Review
Understanding excitation and inhibition balance in the brain begins with the tale of two basic types of neurons, glutamatergic projection neurons and GABAergic interneurons. The diversity of cortical interneurons is contributed by multiple origins in the ventral forebrain, various tangential migration routes, and complicated regulations of intrinsic factors, extrinsic signals, and activities. Abnormalities of interneuron development lead to dysfunction of interneurons and inhibitory circuits, which are highly associated with neurodevelopmental disorders including schizophrenia, autism spectrum disorders, and intellectual disability. In this review, we mainly discuss recent findings on the development of cortical interneuron and on neurodevelopmental disorders related to interneuron dysfunction.
Topics: Cerebral Cortex; Interneurons; Neurons
PubMed: 33844440
DOI: 10.1111/febs.15872 -
Nature Oct 2023The assembly of cortical circuits involves the generation and migration of interneurons from the ventral to the dorsal forebrain, which has been challenging to study at...
The assembly of cortical circuits involves the generation and migration of interneurons from the ventral to the dorsal forebrain, which has been challenging to study at inaccessible stages of late gestation and early postnatal human development. Autism spectrum disorder and other neurodevelopmental disorders (NDDs) have been associated with abnormal cortical interneuron development, but which of these NDD genes affect interneuron generation and migration, and how they mediate these effects remains unknown. We previously developed a platform to study interneuron development and migration in subpallial organoids and forebrain assembloids. Here we integrate assembloids with CRISPR screening to investigate the involvement of 425 NDD genes in human interneuron development. The first screen aimed at interneuron generation revealed 13 candidate genes, including CSDE1 and SMAD4. We subsequently conducted an interneuron migration screen in more than 1,000 forebrain assembloids that identified 33 candidate genes, including cytoskeleton-related genes and the endoplasmic reticulum-related gene LNPK. We discovered that, during interneuron migration, the endoplasmic reticulum is displaced along the leading neuronal branch before nuclear translocation. LNPK deletion interfered with this endoplasmic reticulum displacement and resulted in abnormal migration. These results highlight the power of this CRISPR-assembloid platform to systematically map NDD genes onto human development and reveal disease mechanisms.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Cell Movement; CRISPR-Cas Systems; Gene Editing; Interneurons; Neurodevelopmental Disorders; Organoids; Endoplasmic Reticulum; Prosencephalon; Active Transport, Cell Nucleus
PubMed: 37758944
DOI: 10.1038/s41586-023-06564-w -
Cell Jan 2017The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse...
The deep dorsal horn is a poorly characterized spinal cord region implicated in processing low-threshold mechanoreceptor (LTMR) information. We report an array of mouse genetic tools for defining neuronal components and functions of the dorsal horn LTMR-recipient zone (LTMR-RZ), a role for LTMR-RZ processing in tactile perception, and the basic logic of LTMR-RZ organization. We found an unexpectedly high degree of neuronal diversity in the LTMR-RZ: seven excitatory and four inhibitory subtypes of interneurons exhibiting unique morphological, physiological, and synaptic properties. Remarkably, LTMRs form synapses on between four and 11 LTMR-RZ interneuron subtypes, while each LTMR-RZ interneuron subtype samples inputs from at least one to three LTMR classes, as well as spinal cord interneurons and corticospinal neurons. Thus, the LTMR-RZ is a somatosensory processing region endowed with a neuronal complexity that rivals the retina and functions to pattern the activity of ascending touch pathways that underlie tactile perception.
Topics: Animals; Axons; Dendrites; Interneurons; Mechanoreceptors; Mice; Molecular Biology; Neural Pathways; Spinal Cord; Synapses; Touch Perception
PubMed: 28041852
DOI: 10.1016/j.cell.2016.12.010 -
Nature Oct 2021The cerebellar cortex is a well-studied brain structure with diverse roles in motor learning, coordination, cognition and autonomic regulation. However, a complete...
The cerebellar cortex is a well-studied brain structure with diverse roles in motor learning, coordination, cognition and autonomic regulation. However, a complete inventory of cerebellar cell types is currently lacking. Here, using recent advances in high-throughput transcriptional profiling, we molecularly define cell types across individual lobules of the adult mouse cerebellum. Purkinje neurons showed considerable regional specialization, with the greatest diversity occurring in the posterior lobules. For several types of cerebellar interneuron, the molecular variation within each type was more continuous, rather than discrete. In particular, for the unipolar brush cells-an interneuron population previously subdivided into discrete populations-the continuous variation in gene expression was associated with a graded continuum of electrophysiological properties. Notably, we found that molecular layer interneurons were composed of two molecularly and functionally distinct types. Both types show a continuum of morphological variation through the thickness of the molecular layer, but electrophysiological recordings revealed marked differences between the two types in spontaneous firing, excitability and electrical coupling. Together, these findings provide a comprehensive cellular atlas of the cerebellar cortex, and outline a methodological and conceptual framework for the integration of molecular, morphological and physiological ontologies for defining brain cell types.
Topics: Adult; Animals; Atlases as Topic; Cerebellar Cortex; Electrophysiology; Female; Gene Expression Profiling; Humans; Interneurons; Male; Mice; Mice, Inbred C57BL; Neuroglia; Neurons; Transcriptome
PubMed: 34616064
DOI: 10.1038/s41586-021-03220-z -
Wiley Interdisciplinary Reviews.... Mar 2018First described by Ramon y Cajal as 'short-axon' cells over a century ago, inhibitory interneurons in the cerebral cortex make up ~20-30% of the neuronal milieu. A key... (Review)
Review
First described by Ramon y Cajal as 'short-axon' cells over a century ago, inhibitory interneurons in the cerebral cortex make up ~20-30% of the neuronal milieu. A key feature of these interneurons is the striking structural and functional diversity, which allows them to modulate neural activity in diverse ways and ultimately endow neural circuits with remarkable computational power. Here, we review our current understanding of the generation of cortical interneurons, with a focus on recent efforts to bridge the gap between progenitor behavior and interneuron production, and how these aspects influence interneuron diversity and organization. WIREs Dev Biol 2018, 7:e306. doi: 10.1002/wdev.306 This article is categorized under: Nervous System Development > Vertebrates: General Principles.
Topics: Animals; Cell Lineage; Cerebral Cortex; Interneurons; Neural Inhibition; Neural Stem Cells; Neurogenesis
PubMed: 29115042
DOI: 10.1002/wdev.306 -
European Neuropsychopharmacology : the... May 2024Parvalbumin-expressing (PV+) interneurons represent one of the most abundant subclasses of cortical interneurons. Owing to their specific electrophysiological and... (Review)
Review
Parvalbumin-expressing (PV+) interneurons represent one of the most abundant subclasses of cortical interneurons. Owing to their specific electrophysiological and synaptic properties, PV+ interneurons are essential for gating and pacing the activity of excitatory neurons. In particular, PV+ interneurons are critically involved in generating and maintaining cortical rhythms in the gamma frequency, which are essential for complex cognitive functions. Deficits in PV+ interneurons have been frequently reported in postmortem studies of schizophrenia patients, and alterations in gamma oscillations are a prominent electrophysiological feature of the disease. Here, I summarise the main features of PV+ interneurons and review clinical and preclinical studies linking the developmental dysfunction of cortical PV+ interneurons with the pathophysiology of schizophrenia.
Topics: Interneurons; Parvalbumins; Schizophrenia; Humans; Animals; Gamma Rhythm
PubMed: 38490084
DOI: 10.1016/j.euroneuro.2024.02.010 -
Frontiers in Neural Circuits 2023Cortical GABAergic interneurons are critical components of neural networks. They provide local and long-range inhibition and help coordinate network activities involved... (Review)
Review
Cortical GABAergic interneurons are critical components of neural networks. They provide local and long-range inhibition and help coordinate network activities involved in various brain functions, including signal processing, learning, memory and adaptative responses. Disruption of cortical GABAergic interneuron migration thus induces profound deficits in neural network organization and function, and results in a variety of neurodevelopmental and neuropsychiatric disorders including epilepsy, intellectual disability, autism spectrum disorders and schizophrenia. It is thus of paramount importance to elucidate the specific mechanisms that govern the migration of interneurons to clarify some of the underlying disease mechanisms. GABAergic interneurons destined to populate the cortex arise from multipotent ventral progenitor cells located in the ganglionic eminences and pre-optic area. Post-mitotic interneurons exit their place of origin in the ventral forebrain and migrate dorsally using defined migratory streams to reach the cortical plate, which they enter through radial migration before dispersing to settle in their final laminar allocation. While migrating, cortical interneurons constantly change their morphology through the dynamic remodeling of actomyosin and microtubule cytoskeleton as they detect and integrate extracellular guidance cues generated by neuronal and non-neuronal sources distributed along their migratory routes. These processes ensure proper distribution of GABAergic interneurons across cortical areas and lamina, supporting the development of adequate network connectivity and brain function. This short review summarizes current knowledge on the cellular and molecular mechanisms controlling cortical GABAergic interneuron migration, with a focus on tangential migration, and addresses potential avenues for cell-based interneuron progenitor transplants in the treatment of neurodevelopmental disorders and epilepsy.
Topics: Cerebral Cortex; Neurogenesis; Interneurons; Cell Movement
PubMed: 37779671
DOI: 10.3389/fncir.2023.1256455 -
Brain Research Jan 2017Schizophrenia is a devastating psychiatric disorder characterized by positive, negative and cognitive symptoms. While aberrant dopamine system function is typically... (Review)
Review
Schizophrenia is a devastating psychiatric disorder characterized by positive, negative and cognitive symptoms. While aberrant dopamine system function is typically associated with the positive symptoms of the disease, it is thought that this is secondary to pathology in afferent regions. Indeed, schizophrenia patients show dysregulated activity in the hippocampus and prefrontal cortex, two regions known to regulate dopamine neuron activity. These deficits in hippocampal and prefrontal cortical function are thought to result, in part, from reductions in inhibitory interneuron function in these brain regions. Therefore, it has been hypothesized that restoring interneuron function in the hippocampus and/or prefrontal cortex may be an effective treatment strategy for schizophrenia. In this article, we will discuss the evidence for interneuron pathology in schizophrenia and review recent advances in our understanding of interneuron development. Finally, we will explore how these advances have allowed us to test the therapeutic value of interneuron transplants in multiple preclinical models of schizophrenia. This article is part of a Special Issue entitled SI:StemsCellsinPsychiatry.
Topics: Animals; Brain; Cell Transplantation; Humans; Interneurons; Schizophrenia
PubMed: 27544423
DOI: 10.1016/j.brainres.2016.08.010