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PLoS Biology Nov 2022The striatum links neuronal circuits in the human brain, and its malfunction causes neuronal disorders such as Huntington's disease (HD). A human striatum model that...
The striatum links neuronal circuits in the human brain, and its malfunction causes neuronal disorders such as Huntington's disease (HD). A human striatum model that recapitulates fetal striatal development is vital to decoding the pathogenesis of striatum-related neurological disorders and developing therapeutic strategies. Here, we developed a method to construct human striatal organoids (hStrOs) from human pluripotent stem cells (hPSCs), including hStrOs-derived assembloids. Our hStrOs partially replicated the fetal striatum and formed striosome and matrix-like compartments in vitro. Single-cell RNA sequencing revealed distinct striatal lineages in hStrOs, diverging from dorsal forebrain fate. Using hStrOs-derived assembloids, we replicated the striatal targeting projections from different brain parts. Furthermore, hStrOs can serve as hosts for striatal neuronal allografts to test allograft neuronal survival and functional integration. Our hStrOs are suitable for studying striatal development and related disorders, characterizing the neural circuitry between different brain regions, and testing therapeutic strategies.
Topics: Humans; Organoids; Pluripotent Stem Cells; Corpus Striatum; Neostriatum; Prosencephalon
PubMed: 36395338
DOI: 10.1371/journal.pbio.3001868 -
Brain, Behavior and Evolution 2022The neuromeric/prosomeric model has been rejuvenated by Puelles and Rubenstein [Trends Neurosci. 1993;16(11):472-9]. Here, its application to the (teleostean) fish brain... (Review)
Review
The neuromeric/prosomeric model has been rejuvenated by Puelles and Rubenstein [Trends Neurosci. 1993;16(11):472-9]. Here, its application to the (teleostean) fish brain is detailed, beginning with a historical account. The second part addresses three main issues with particular interest for fish neuroanatomy and looks at the impact of the neuromeric model on their understanding. The first one is the occurrence of four early migrating forebrain areas (M1 through M4) in teleosts and their comparative interpretation. The second issue addresses the complex development and neuroanatomy of the teleostean alar and basal hypothalamus. The third topic is the vertebrate dopaminergic system, with the focus on some teleostean peculiarities. Most of the information will be coming from zebrafish studies, although the general ductus is a comparative one. Throughout the manuscript, comparative developmental and organizational aspects of the teleostean amygdala are discussed. One particular focus is cellular migration streams into the medial amygdala.
Topics: Animals; Zebrafish; Neurobiology; Prosencephalon; Dopamine
PubMed: 35728561
DOI: 10.1159/000525607 -
Frontiers in Endocrinology 2023AXL is a receptor tyrosine kinase commonly associated with a variety of human cancers. Along with its ligand Gas6 (growth arrest-specific protein 6), AXL is emerging as... (Review)
Review
AXL is a receptor tyrosine kinase commonly associated with a variety of human cancers. Along with its ligand Gas6 (growth arrest-specific protein 6), AXL is emerging as an important regulator of neuroendocrine development and function. AXL signaling in response to Gas6 binding impacts neuroendocrine structure and function at the level of the brain, pituitary, and gonads. During development, AXL has been identified as an upstream inhibitor of gonadotropin receptor hormone (GnRH) production and also plays a key role in the migration of GnRH neurons from the olfactory placode to the forebrain. AXL is implicated in reproductive diseases including some forms of idiopathic hypogonadotropic hypogonadism and evidence suggests that AXL is required for normal spermatogenesis. Here, we highlight research describing AXL/Gas6 signaling mechanisms with a focus on the molecular pathways related to neuroendocrine function in health and disease. In doing so, we aim to present a concise account of known AXL/Gas6 signaling mechanisms to identify current knowledge gaps and inspire future research.
Topics: Humans; Male; Axl Receptor Tyrosine Kinase; Gonadotropin-Releasing Hormone; Hypothalamic-Pituitary-Gonadal Axis; Prosencephalon; Proto-Oncogene Proteins
PubMed: 37396176
DOI: 10.3389/fendo.2023.1212104 -
Cerebral Cortex (New York, N.Y. : 1991) Mar 2023The effective connectivity between 55 visual cortical regions and 360 cortical regions was measured in 171 HCP participants using the HCP-MMP atlas, and complemented...
The effective connectivity between 55 visual cortical regions and 360 cortical regions was measured in 171 HCP participants using the HCP-MMP atlas, and complemented with functional connectivity and diffusion tractography. A Ventrolateral Visual "What" Stream for object and face recognition projects hierarchically to the inferior temporal visual cortex, which projects to the orbitofrontal cortex for reward value and emotion, and to the hippocampal memory system. A Ventromedial Visual "Where" Stream for scene representations connects to the parahippocampal gyrus and hippocampus. An Inferior STS (superior temporal sulcus) cortex Semantic Stream receives from the Ventrolateral Visual Stream, from visual inferior parietal PGi, and from the ventromedial-prefrontal reward system and connects to language systems. A Dorsal Visual Stream connects via V2 and V3A to MT+ Complex regions (including MT and MST), which connect to intraparietal regions (including LIP, VIP and MIP) involved in visual motion and actions in space. It performs coordinate transforms for idiothetic update of Ventromedial Stream scene representations. A Superior STS cortex Semantic Stream receives visual inputs from the Inferior STS Visual Stream, PGi, and STV, and auditory inputs from A5, is activated by face expression, motion and vocalization, and is important in social behaviour, and connects to language systems.
Topics: Humans; Visual Pathways; Temporal Lobe; Visual Cortex; Hippocampus; Prefrontal Cortex; Parietal Lobe; Brain Mapping
PubMed: 35834308
DOI: 10.1093/cercor/bhac276 -
Cell Reports Jul 2023Rare genetic variants in ANK2, which encodes ankyrin-B, are associated with neurodevelopmental disorders (NDDs); however, their pathogenesis is poorly understood. We...
Rare genetic variants in ANK2, which encodes ankyrin-B, are associated with neurodevelopmental disorders (NDDs); however, their pathogenesis is poorly understood. We find that mice with prenatal deletion in cortical excitatory neurons and oligodendrocytes (Ank2:Emx1-Cre), but not with adolescent deletion in forebrain excitatory neurons (Ank2:CaMKIIα-Cre), display severe spontaneous seizures, increased mortality, hyperactivity, and social deficits. Calcium imaging of cortical slices from Ank2:Emx1-Cre mice shows increased neuronal calcium event amplitude and frequency, along with network hyperexcitability and hypersynchrony. Quantitative proteomic analysis of cortical synaptic membranes reveals upregulation of dendritic spine plasticity-regulatory proteins and downregulation of intermediate filaments. Characterization of the ankyrin-B interactome identifies interactors associated with autism and epilepsy risk factors and synaptic proteins. The AMPA receptor antagonist, perampanel, restores cortical neuronal activity and partially rescues survival in Ank2:Emx1-Cre mice. Our findings suggest that synaptic proteome alterations resulting from Ank2 deletion impair neuronal activity and synchrony, leading to NDDs-related behavioral impairments.
Topics: Animals; Mice; Ankyrins; Calcium; Phenotype; Prosencephalon; Proteome; Proteomics; Seizures; Mice, Knockout
PubMed: 37428632
DOI: 10.1016/j.celrep.2023.112784 -
Anatomical Science International Jun 2021Neuronal circuits in the neocortex and hippocampus are essential for higher brain functions such as motor learning and spatial memory. In the mammalian forebrain, most... (Review)
Review
Neuronal circuits in the neocortex and hippocampus are essential for higher brain functions such as motor learning and spatial memory. In the mammalian forebrain, most excitatory synapses of pyramidal neurons are formed on spines, which are tiny protrusions extending from the dendritic shaft. The spine contains specialized molecular machinery that regulates synaptic transmission and plasticity. Spine size correlates with the efficacy of synaptic transmission, and spine morphology affects signal transduction at the post-synaptic compartment. Plasticity-related changes in the structural and molecular organization of spine synapses are thought to underlie the cellular basis of learning and memory. Recent advances in super-resolution microscopy have revealed the molecular mechanisms of the nanoscale synaptic structures regulating synaptic transmission and plasticity in living neurons, which are difficult to investigate using electron microscopy alone. In this review, we summarize recent advances in super-resolution imaging of spine synapses and discuss the implications of nanoscale structures in the regulation of synaptic function, learning, and memory.
Topics: Animals; Dendritic Spines; Humans; Microscopy; Neuronal Plasticity; Neurons; Prosencephalon; Synapses; Synaptic Transmission
PubMed: 33459976
DOI: 10.1007/s12565-021-00603-0 -
Neuroscience Aug 2022For decades, Izquierdo and colleagues contributed to building the notion that declarative memory requires different processes at the molecular and systems levels. This... (Review)
Review
For decades, Izquierdo and colleagues contributed to building the notion that declarative memory requires different processes at the molecular and systems levels. This review aims to discuss part of Izquierdo's legacy, mainly but not exclusively that related to fear memory. First, some of the philosophical and evolutionary issues that arise from declarative memory definition are presented. Then, the underlying processes of declarative memory are depicted, discussing the formation, the nature and the progression of the memory trace in short-term and long-term memory, and describing the involvement of some molecular cascades in the hippocampal formation, mesocortex and frontal areas. Potential contributions to therapy or understanding cognitive processes are mentioned.
Topics: Cerebral Cortex; Fear; Hippocampus; Memory, Long-Term; Prefrontal Cortex
PubMed: 35314250
DOI: 10.1016/j.neuroscience.2022.03.015 -
Progress in Neuro-psychopharmacology &... Aug 2023Memories of everyday experiences involve the encoding of a rich and dynamic representation of present objects and their contextual features. Traditionally, the resulting... (Review)
Review
Memories of everyday experiences involve the encoding of a rich and dynamic representation of present objects and their contextual features. Traditionally, the resulting mnemonic trace is referred to as Episodic Memory, i.e. the "what", "where" and "when" of a lived episode. The journey for such memory trace encoding begins with the perceptual data of an experienced episode handled in sensory brain regions. The information is then streamed to cortical areas located in the ventral Medio Temporal Lobe, which produces multi-modal representations concerning either the objects (in the Perirhinal cortex) or the spatial and contextual features (in the parahippocampal region) of the episode. Then, this high-level data is gated through the Entorhinal Cortex and forwarded to the Hippocampal Formation, where all the pieces get bound together. Eventually, the resulting encoded neural pattern is relayed back to the Neocortex for a stable consolidation. This review will detail these different stages and provide a systematic overview of the major cortical streams toward the Hippocampus relevant for Episodic Memory encoding.
Topics: Memory, Episodic; Hippocampus; Entorhinal Cortex; Temporal Lobe; Neural Pathways
PubMed: 37086812
DOI: 10.1016/j.pnpbp.2023.110757 -
Scientific Reports May 2022Coral reef fish exhibit a large variety of behaviours crucial for fitness and survival. The cleaner wrasse Labroides dimidiatus displays cognitive abilities during...
Coral reef fish exhibit a large variety of behaviours crucial for fitness and survival. The cleaner wrasse Labroides dimidiatus displays cognitive abilities during interspecific interactions by providing services of ectoparasite cleaning, thus serving as a good example to understand the processes of complex social behaviour. However, little is known about the molecular underpinnings of cooperative behaviour between L. dimidiatus and a potential client fish (Acanthurus leucosternon). Therefore, we investigated the molecular mechanisms in three regions of the brain (Fore-, Mid-, and Hindbrain) during the interaction of these fishes. Here we show, using transcriptomics, that most of the transcriptional response in both species was regulated in the Hindbrain and Forebrain regions and that the interacting behaviour responses of L. dimidiatus involved immediate early gene alteration, dopaminergic and glutamatergic pathways, the expression of neurohormones (such as isotocin) and steroids (e.g. progesterone and estrogen). In contrast, in the client, fewer molecular alterations were found, mostly involving pituitary hormone responses. The particular pathways found suggested synaptic plasticity, learning and memory processes in the cleaner wrasse, while the client indicated stress relief.
Topics: Animals; Coral Reefs; Fishes; Perciformes; Prosencephalon; Social Behavior
PubMed: 35589869
DOI: 10.1038/s41598-022-12363-6 -
Science (New York, N.Y.) Oct 2019Although language, and therefore spoken language or speech, is often considered unique to humans, the past several decades have seen a surge in nonhuman animal studies... (Review)
Review
Although language, and therefore spoken language or speech, is often considered unique to humans, the past several decades have seen a surge in nonhuman animal studies that inform us about human spoken language. Here, I present a modern, evolution-based synthesis of these studies, from behavioral to molecular levels of analyses. Among the key concepts drawn are that components of spoken language are continuous between species, and that the vocal learning component is the most specialized and rarest and evolved by brain pathway duplication from an ancient motor learning pathway. These concepts have important implications for understanding brain mechanisms and disorders of spoken language.
Topics: Animals; Auditory Cortex; Biological Evolution; Brain; Brain Stem; Humans; Language; Learning; Motor Cortex; Neural Pathways; Neurons; Prosencephalon; Speech; Transcriptome; Vocalization, Animal
PubMed: 31604300
DOI: 10.1126/science.aax0287