Development and Functional Diversification of Cortical Interneurons

Lim, Lynette; Mi, Da; Llorca, Alfredo; Marı́n, Oscar

doi:10.1016/j.neuron.2018.10.009

Cited by 561 publications

(566 citation statements)

References 194 publications

(299 reference statements)

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“…Inhibitory interneurons originating from progenitors within the germinal zones of the ventral telencephalon migrate tangentially and then radially to become allocated to the developing CP. Among two large migratory streams, MZ and SVZ, SST+ Martinotti and PV+ interneurons preferentially migrate through the MZ (Lim, Mi, Llorca, & Marin, ). Martinotti cells are known to be positive for the calcium‐binding proteins calbindin and calretinin and are abundant in Layer 5 or Layers 2/3.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, VIP+ interneurons, which are enriched in Layer 2/3, often coexpress calretinin. The incorporation of interneurons to the CP consistently occurs until postnatal stages in mice (Lim et al, ). Furthermore, CGE‐derived interneurons are disposed to target superficial layers regardless of their birth date (Miyoshi et al, ; Miyoshi & Fishell, ).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the PCZ is initially found around E16.5 in mouse neocortex. stages in mice (Lim et al, 2018). Furthermore, CGE-derived interneurons are disposed to target superficial layers regardless of their birth date (Miyoshi et al, 2010;Miyoshi & Fishell, 2011).…”

Section: Discussionmentioning

confidence: 99%

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Both excitatory and inhibitory neurons transiently form clusters at the outermost region of the developing mammalian cerebral neocortex

Shin

Kitazawa

Yoshinaga

et al. 2019

J of Comparative Neurology

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During development of the mammalian cerebral neocortex, postmitotic excitatory neurons migrate toward the outermost region of the neocortex. We previously reported that this outermost region is composed of densely packed relatively immature neurons; we named this region, which is observed during the late stage of mouse neocortical development, the “primitive cortical zone (PCZ).” Here, we report that postmigratory immature neurons spend about 1–1.5 days in the PCZ. An electron microscopic analysis showed that the neurons in the PCZ tend to be in direct contact with each other, mostly in a radial direction, forming “primitive neuronal clusters” with a height of 3–7 cells and a width of 1–2 cells. A time‐course analysis of fluorescently labeled neurons revealed that the neurons took their positions within the primitive clusters in an inside‐out manner. The neurons initially participated in the superficial part of the clusters, gradually shifted their relative positions downward, and then left the clusters at the bottom of this structure. GABAergic inhibitory interneurons were also found within the primitive clusters in the developing mouse neocortex, suggesting that some clusters are composed of both excitatory neurons and inhibitory interneurons. Similar clusters were also observed in the outermost region of embryonic day (E) 78 cynomolgus monkey occipital cortex and 23 gestational week (GW) human neocortices. In the primate neocortices, including human, the presumptive primitive clusters seemed to expand in the radial direction more than that observed in mice, which might contribute to the functional integrity of the primate neocortex.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Both excitatory and inhibitory neurons transiently form clusters at the outermost region of the developing mammalian cerebral neocortex

Shin

Kitazawa

Yoshinaga

et al. 2019

J of Comparative Neurology

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“…Alternatively, altered dopamine sensitivity of Foxp2 cKO excitatory projection neurons may prevent the activity-dependent apoptosis of these interneurons, which normally occurs around the postnatal time point examined in our study (Lim et al 2018). Integration of these excess interneurons into cortical circuits could then impair circuit function and lead to behavioral deficits.…”

Section: Foxp2-regulated Cortical Dopamine Signaling and Behavioral Fmentioning

confidence: 83%

Cortical Foxp2 supports behavioral flexibility and developmental dopamine D1 receptor expression

Hickey

Kulkarni

et al. 2019

Preprint

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FoxP2 encodes a forkhead box transcription factor required for the development of neural circuits underlying language, vocalization, and motor-skill learning. Human genetic studies have associated FOXP2 variation with neurodevelopmental disorders (NDDs), and within the cortex, it is coexpressed and interacts with other NDD-associated transcription factors. Cortical Foxp2 is required in mice for proper social interactions, but its role in other NDD-relevant behaviors and molecular pathways is unknown. Here, we characterized such behaviors and their potential underlying cellular and molecular mechanisms in cortex-specific Foxp2 conditional knockout mice. These mice showed deficits in reversal learning without increased anxiety or hyperactivity. In contrast, they emitted normal vocalizations save for a decrease in loudness of neonatal calls. These behavioral phenotypes were accompanied by decreases in cortical dopamine D1 receptor (D1R) expression at neonatal and adult stages, while general cortical development remained unaffected. Finally, using single-cell transcriptomics, we identified neonatal D1R-expressing cell types in frontal cortex and found changes in D1R cell type composition and gene expression upon cortical Foxp2 deletion. Together these data support a role for Foxp2 in the development of dopamine-modulated cortical circuits potentially relevant to NDDs.

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“…Upon leaving their birthplaces, the inhibitory neurons invade the dorsal forebrain and migrate tangentially in the subventricular zone and marginal zone (MZ; the most superficial area of the neocortex and future Layer I) in the neocortex, and then enter the cortical plate (CP; future gray matter), interact with the excitatory neurons, and become distributed among the latter. [80][81][82] Since inhibitory neurons migrate longer distances to reach their final destinations than excitatory neurons, they might be more susceptible to various factors that affect neuronal migration. 83 As mentioned above, Yang et al found a significant negative correlation between the mRNA expression of somatostatin in the gray matter and the densities of NeuN-positive neurons in the WM.…”

Section: Migration Failure Of Gabaergic Neuronsmentioning

confidence: 99%

Increased densities of white matter neurons as a cross‐disease feature of neuropsychiatric disorders

Kubo

2020

Psychiatry Clin Neurosci

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While neurons of the human cerebral cortex are mainly distributed in the gray matter, the white matter (WM) also contains some excitatory and inhibitory neurons, so‐called WM neurons. Studies on the cytoarchitectural alterations in the brains of patients with neuropsychiatric disorders have repeatedly reported increased densities of the WM neurons in a proportion of patients with schizophrenia and autism spectrum disorder. Although some studies have demonstrated increased densities of superficial WM neurons, others have demonstrated increased densities of deep WM neurons and increased WM neuron densities can be considered as one of the cross‐disease features of neuropsychiatric disorders. Nevertheless, what actually causes the increase in the densities of the WM neurons still remains under debate, and several hypothetical mechanisms have been proposed. The WM neurons in normal brains are considered as remnants of the subplate neurons, which represent a transient cytoarchitectural zone present during development of the mammalian neocortex; it has been suggested that increased densities of the WM neurons could result from inappropriate apoptosis of the subplate neurons in the brains of patients with neuropsychiatric disorders. On the other hand, recent experimental studies have demonstrated that genetic and environmental factors that enhance the risk of development of neuropsychiatric disorders could cause altered distribution of neurons in the WM. To understand the pathophysiology underlying the increased densities of the WM neurons, it is important to investigate the cellular characteristics of the WM neurons in the brains of both normal subjects and patients with neuropsychiatric disorders.

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Development and Functional Diversification of Cortical Interneurons

Cited by 561 publications

References 194 publications

Both excitatory and inhibitory neurons transiently form clusters at the outermost region of the developing mammalian cerebral neocortex

Both excitatory and inhibitory neurons transiently form clusters at the outermost region of the developing mammalian cerebral neocortex

Cortical Foxp2 supports behavioral flexibility and developmental dopamine D1 receptor expression

Increased densities of white matter neurons as a cross‐disease feature of neuropsychiatric disorders

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