scholarly journals Maternal inflammation has a profound effect on cortical interneuron development in a stage and subtype-specific manner

2018 ◽  
Author(s):  
Navneet A. Vasistha ◽  
Maria Pardo-Navarro ◽  
Janina Gasthaus ◽  
Dilys Weijers ◽  
Michaela K. Müller ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Selective Vulnerability ◽  
Gabaergic Interneuron ◽  
Gabaergic Interneurons ◽  
Affected Offspring ◽  
Inhibitory Circuits ◽  
Maternal Inflammation ◽  
Mature Brain ◽  
Cortical Regions ◽  
Interneuron Development

AbstractSevere infections during pregnancy are one of the major risk factors for cognitive brain impairment in offspring. It has been suggested that maternal inflammation leads to dysfunction of cortical GABAergic interneurons that in turn underlies cognitive impairment of the affected offspring. However, the evidence comes largely from studies of adult or mature brain and how impairment of inhibitory circuits arises upon maternal inflammation is unknown. Here we show that maternal inflammation affects multiple steps of cortical GABAergic interneuron development, i.e. proliferation of precursor cells, migration and positioning of neuroblasts as well as neuronal maturation. Importantly, the development of distinct subtypes of cortical GABAergic interneurons was discretely impaired as a result of maternal inflammation. This translated into a reduction in cell numbers, redistribution across cortical regions and layers, changes in morphology and cellular properties. Furthermore, selective vulnerability of GABAergic interneuron subtypes was associated with the stage of brain development. Thus, we propose that maternally-derived insults have developmental stage-dependent effects which contribute to the complex etiology of cognitive impairment in the affected offspring.

scholarly journals Maternal inflammation has a profound effect on cortical interneuron development in a stage and subtype-specific manner

2019 ◽  
Vol 25 (10) ◽  
pp. 2313-2329 ◽  
Author(s):  
Navneet A. Vasistha ◽  
Maria Pardo-Navarro ◽  
Janina Gasthaus ◽  
Dilys Weijers ◽  
Michaela K. Müller ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Selective Vulnerability ◽  
Gabaergic Interneuron ◽  
Gabaergic Interneurons ◽  
Affected Offspring ◽  
Cortical Interneuron ◽  
Inhibitory Circuits ◽  
Maternal Inflammation ◽  
Cortical Regions ◽  
Interneuron Development

Abstract Severe infections during pregnancy are one of the major risk factors for cognitive impairment in the offspring. It has been suggested that maternal inflammation leads to dysfunction of cortical GABAergic interneurons that in turn underlies cognitive impairment of the affected offspring. However, the evidence comes largely from studies of adult or mature brains and how the impairment of inhibitory circuits arises upon maternal inflammation is unknown. Here we show that maternal inflammation affects multiple steps of cortical GABAergic interneuron development, i.e., proliferation of precursor cells, migration and positioning of neuroblasts, as well as neuronal maturation. Importantly, the development of distinct subtypes of cortical GABAergic interneurons was discretely impaired as a result of maternal inflammation. This translated into a reduction in cell numbers, redistribution across cortical regions and layers, and changes in morphology and cellular properties. Furthermore, selective vulnerability of GABAergic interneuron subtypes was associated with the stage of brain development. Thus, we propose that maternally derived insults have developmental stage-dependent effects, which contribute to the complex etiology of cognitive impairment in the affected offspring.

scholarly journals Implications of Extended Inhibitory Neuron Development

2021 ◽  
Vol 22 (10) ◽  
pp. 5113
Author(s):  
Jae-Yeon Kim ◽  
Mercedes F. Paredes
Keyword(s):  
Neural Circuit ◽  
Inhibitory Neuron ◽  
Postnatal Period ◽  
Specific Pattern ◽  
Inhibitory Neurons ◽  
Gabaergic Interneuron ◽  
Gabaergic Interneurons ◽  
Neuron Development ◽  
Cortical Regions ◽  
Circuit Formation

A prolonged developmental timeline for GABA (γ-aminobutyric acid)-expressing inhibitory neurons (GABAergic interneurons) is an amplified trait in larger, gyrencephalic animals. In several species, the generation, migration, and maturation of interneurons take place over several months, in some cases persisting after birth. The late integration of GABAergic interneurons occurs in a region-specific pattern, especially during the early postnatal period. These changes can contribute to the formation of functional connectivity and plasticity, especially in the cortical regions responsible for higher cognitive tasks. In this review, we discuss GABAergic interneuron development in the late gestational and postnatal forebrain. We propose the protracted development of interneurons at each stage (neurogenesis, neuronal migration, and network integration), as a mechanism for increased complexity and cognitive flexibility in larger, gyrencephalic brains. This developmental feature of interneurons also provides an avenue for environmental influences to shape neural circuit formation.

Endocannabinoid system in the neurodevelopment of GABAergic interneurons: implications for neurological and psychiatric disorders

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Chang-geng Song ◽  
Xin Kang ◽  
Fang Yang ◽  
Wan-qing Du ◽  
Jia-jia Zhang ◽  
...  
Keyword(s):  
Psychiatric Disorders ◽  
Endocannabinoid System ◽  
Autism Spectrum ◽  
Network Activity ◽  
Inhibitory Neurons ◽  
Gabaergic Interneurons ◽  
Neural Stem Progenitor Cells ◽  
The Central Nervous System ◽  
Interneuron Development

Abstract In mature mammalian brains, the endocannabinoid system (ECS) plays an important role in the regulation of synaptic plasticity and the functioning of neural networks. Besides, the ECS also contributes to the neurodevelopment of the central nervous system. Due to the increase in the medical and recreational use of cannabis, it is inevitable and essential to elaborate the roles of the ECS on neurodevelopment. GABAergic interneurons represent a group of inhibitory neurons that are vital in controlling neural network activity. However, the role of the ECS in the neurodevelopment of GABAergic interneurons remains to be fully elucidated. In this review, we provide a brief introduction of the ECS and interneuron diversity. We focus on the process of interneuron development and the role of ECS in the modulation of interneuron development, from the expansion of the neural stem/progenitor cells to the migration, specification and maturation of interneurons. We further discuss the potential implications of the ECS and interneurons in the pathogenesis of neurological and psychiatric disorders, including epilepsy, schizophrenia, major depressive disorder and autism spectrum disorder.

scholarly journals Transcriptional regulation of MGE progenitor proliferation by PRDM16 controls cortical GABAergic interneuron production

Development ◽  
2020 ◽  
Vol 147 (22) ◽  
pp. dev187526
Author(s):  
Miguel Turrero García ◽  
José-Manuel Baizabal ◽  
Diana N. Tran ◽  
Rui Peixoto ◽  
Wengang Wang ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Radial Glia ◽  
Regulatory Elements ◽  
Neural Progenitors ◽  
Gabaergic Interneuron ◽  
Gabaergic Interneurons ◽  
Proliferative Capacity ◽  
Medial Ganglionic Eminence ◽  
Developmental Gene Expression ◽  
Dorsal Telencephalon

ABSTRACTThe mammalian cortex is populated by neurons derived from neural progenitors located throughout the embryonic telencephalon. Excitatory neurons are derived from the dorsal telencephalon, whereas inhibitory interneurons are generated in its ventral portion. The transcriptional regulator PRDM16 is expressed by radial glia, neural progenitors present in both regions; however, its mechanisms of action are still not fully understood. It is unclear whether PRDM16 plays a similar role in neurogenesis in both dorsal and ventral progenitor lineages and, if so, whether it regulates common or unique networks of genes. Here, we show that Prdm16 expression in mouse medial ganglionic eminence (MGE) progenitors is required for maintaining their proliferative capacity and for the production of proper numbers of forebrain GABAergic interneurons. PRDM16 binds to cis-regulatory elements and represses the expression of region-specific neuronal differentiation genes, thereby controlling the timing of neuronal maturation. PRDM16 regulates convergent developmental gene expression programs in the cortex and MGE, which utilize both common and region-specific sets of genes to control the proliferative capacity of neural progenitors, ensuring the generation of correct numbers of cortical neurons.

scholarly journals Changes in resting-state Functional Connectivity of Cerebellum in amnestic Mild Cognitive Impairment and Alzheimer’s disease: a case-control study

2020 ◽  
Author(s):  
Zhi Zhou ◽  
Rui Zhu ◽  
Wen Shao ◽  
Shujuan Zhang ◽  
Lei Wang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Functional Connectivity ◽  
Resting State ◽  
Case Control Study ◽  
Case Control ◽  
Amnestic Mild Cognitive Impairment ◽  
Crus I ◽  
Cortical Regions ◽  
Control Study

Abstract Background This case-control study is aimed to investigate the correlation of altered functional connectivity (FC) in cerebellum with cognitive impairment in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD).Methods The morphometric and resting-state FC MRI analysis including 47 participants with AD, 32 with aMCI and 43 age-matched normal controls (NCs) were conducted. We compared the cerebellar gray matter volume and cerebellar FC with cerebral cortical regions among three groups. To investigate the relationship of cerebellar FC with cognition, we measure the correlation of significant altered FC and individual cognitive domain.Results No significant morphometric differences of cerebellum was observed across three groups. The patients with AD had weaker cerebral cortical FCs in bilateral Crus I, left VIIb and IX compared to NCs, and in bilateral Crus I compared to patients with aMCI. For patients with aMCI, the weaker FC were found between right Crus I, left VIIb and IX and cerebral cortical regions compared to NCs. The strength of left cerebellar FC positively correlated with specific cognitive subdomains, including executive function, attention, visuospatial function, and global cognition in AD and aMCI.Conclusions These findings demonstrated the alteration of cerebellar FC with cerebral cortical regions, and the correlation of cerebellar FC and cognitive impairment in AD and aMCI.

scholarly journals Functional signature of conversion in Mild Cognitive Impairment patients

2018 ◽  
Author(s):  
Stefano Delli Pizzi ◽  
Miriam Punzi ◽  
Stefano L Sensi ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Brain Atrophy ◽  
Cortical Atrophy ◽  
Study Cohort ◽  
Dramatic Decline ◽  
Healthy Control ◽  
Cortical Regions

AbstractThe entorhinal-hippocampal circuit is a strategic hub for memory but also the first site to be affected in the Alzheimer’s Disease (AD)-related pathology. We investigated MRI patterns of brain atrophy and functional connectivity in a study cohort obtained from the Alzheimer’s Disease Neuroimaging Initiative database including healthy control (HC), Mild Cognitive Impairment (MCI), and AD subjects. MCI individuals were clinically evaluated 24 months after the MRI scan, and the group further divided into a subset of subjects who either did (c-MCI) or did not (nc-MCI) convert to AD. Compared to HC subjects, AD patients exhibited a collapse of long-range connectivity from the hippocampus and entorhinal cortex, pronounced cortical/sub-cortical atrophy, and a dramatic decline in cognitive performances. c-MCI patients showed entorhinal and hippocampal hypo-connectivity, no signs of cortical thinning but evidence of right hippocampus atrophy. On the contrary, nc-MCI patients showed lack of brain atrophy, largely preserved cognitive functions, hippocampal and entorhinal hyper-connectivity with selected neocortical/sub-cortical regions mainly involved in memory processing and brain meta-stability. This hyper-connectivity can represent an early compensatory strategy to overcome the progression of cognitive impairment. This functional signature can also be employed for the diagnosis of c-MCI subjects.

scholarly journals Changes in Resting-State Functional Connectivity of Cerebellum in Amnestic Mild Cognitive Impairment and Alzheimer’s Disease: A Case-Control Study

2021 ◽  
Vol 15 ◽  
Author(s):  
Zhi Zhou ◽  
Rui Zhu ◽  
Wen Shao ◽  
Shu-juan Zhang ◽  
Lei Wang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Functional Connectivity ◽  
Resting State ◽  
Case Control Study ◽  
Case Control ◽  
Amnestic Mild Cognitive Impairment ◽  
Crus I ◽  
Cortical Regions ◽  
Control Study

This case-control study is aimed to investigate the correlation of altered functional connectivity (FC) in cerebellum with cognitive impairment in amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD). The morphometric and resting-state FC MRI analysis including 46 participants with AD, 32 with aMCI and 42 age-matched normal controls (NCs) were conducted. We compared the cerebellar gray matter volume and cerebellar FC with cerebral cortical regions among three groups. To investigate the relationship of cerebellar FC with cognition, we measure the correlation of significant altered FC and individual cognitive domain. No significant morphometric differences of cerebellum was observed across three groups. The patients with AD had weaker cerebral cortical FCs in bilateral Crus I and left VIIb compared to NCs, and in bilateral Crus I compared to patients with aMCI. For patients with aMCI, the weaker FC were found between right Crus I, left VIIb and cerebral cortical regions compared to NCs. The strength of left cerebellar FC positively correlated with specific cognitive subdomains, including memory, executive function, visuospatial function, and global cognition in AD and aMCI. These findings demonstrated the alteration of cerebellar FC with cerebral cortical regions, and the correlation of cerebellar FC and cognitive impairment in AD and aMCI.

scholarly journals GABAergic interneurons excite neonatal hippocampus in vivo

2020 ◽  
Vol 6 (24) ◽  
pp. eaba1430 ◽  
Author(s):  
Yasunobu Murata ◽  
Matthew T. Colonnese
Keyword(s):  
Visual Cortex ◽  
Synapse Formation ◽  
Reversal Potential ◽  
Pyramidal Cells ◽  
Gabaergic Neurons ◽  
Network Activity ◽  
Gabaergic Interneuron ◽  
Gabaergic Interneurons ◽  
Early Postnatal Development

GABAergic interneurons are proposed to be critical for early activity and synapse formation by directly exciting, rather than inhibiting, neurons in developing hippocampus and neocortex. However, the role of GABAergic neurons in the generation of neonatal network activity has not been tested in vivo, and recent studies have challenged the excitatory nature of early GABA. By locally manipulating interneuron activity in unanesthetized neonatal mice, we show that GABAergic neurons are excitatory in CA1 hippocampus at postnatal day 3 (P3) and are responsible for most of the spontaneous firing of pyramidal cells at that age. Hippocampal interneurons become inhibitory by P7, whereas visual cortex interneurons are already inhibitory by P3 and remain so throughout development. These regional and age-specific differences are the result of a change in chloride reversal potential, because direct activation of light-gated anion channels in glutamatergic neurons drives CA1 firing at P3, but silences it at P7 in CA1, and at all ages in visual cortex. This study in the intact brain reveals that GABAergic interneuron excitation is essential for network activity in neonatal hippocampus and confirms that visual cortical interneurons are inhibitory throughout early postnatal development.

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