GABAergic Restriction of Network Dynamics Regulates Interneuron Survival in the Developing Cortex

Duan, Zhe Ran S.; Che, Alicia; Chu, Philip; Mòdol, Laura; Bollmann, Yannick; Babij, Rachel; Fetcho, Robert N.; Otsuka, Takumi; Fuccillo, Marc V.; Liston, Conor; Pisapia, David; Cossart, Rosa; García, Natalia V. De Marco

doi:10.1016/j.neuron.2019.10.008

Cited by 81 publications

(103 citation statements)

References 83 publications

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“…Brain cells undergo massive elimination during two waves of apoptosis that take place from the embryonic stage E14 and between P6 and P10 in mice ( Figure 2 ; for review Wong and Marin, 2019 ). In contrast to previously reported cell-autonomous regulation of cell death (Southwell et al, 2012 ), new evidence suggests that specific patterns of postnatal network activity establish the onset, duration and extent of neuronal apoptosis (Blanquie et al, 2017 ; Denaxa et al, 2018 ; Priya et al, 2018 ; Wong et al, 2018 ; Duan et al, 2020 ). Recent work identified two molecular pathways guiding the selection process that determines neuron survival and sets the final composition of a neural network in the cerebral cortex: the calcium-dependent phosphatase Calcineurin, that translates the arrival of electrical activity into molecular cascades of cell survival (Priya et al, 2018 ), and the phosphatase tensin homolog protein (PTEN), that sets the clock for the death of the GABAergic interneurons in the absence of incoming activity from pyramidal neurons (Wong et al, 2018 ).…”

Section: Classical Critical Periods and Critical Periods For Network mentioning

confidence: 74%

Shifting Developmental Trajectories During Critical Periods of Brain Formation

Dehorter

Pino

2020

Front. Cell. Neurosci.

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Critical periods of brain development are epochs of heightened plasticity driven by environmental influence necessary for normal brain function. Recent studies are beginning to shed light on the possibility that timely interventions during critical periods hold potential to reorient abnormal developmental trajectories in animal models of neurological and neuropsychiatric disorders. In this review, we re-examine the criteria defining critical periods, highlighting the recently discovered mechanisms of developmental plasticity in health and disease. In addition, we touch upon technological improvements for modeling critical periods in human-derived neural networks in vitro . These scientific advances associated with the use of developmental manipulations in the immature brain of animal models are the basic preclinical systems that will allow the future translatability of timely interventions into clinical applications for neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD) and schizophrenia.

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Section: Classical Critical Periods and Critical Periods For Network mentioning

confidence: 74%

Shifting Developmental Trajectories During Critical Periods of Brain Formation

Dehorter

Pino

2020

Front. Cell. Neurosci.

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“…Furthermore, GABAergic signaling is required for activity-dependent wiring of the developing cortex (Che et al, 2018;Duan et al, 2019;Marques-Smith et al, 2016;Modol et al, 2019;Oh et al, 2016;Tuncdemir et al, 2016). Here, we investigated how inhibitory signaling shapes spontaneous event patterning in V1 before eye opening.…”

Section: Introductionmentioning

confidence: 99%

Control of spontaneous activity patterns by inhibitory signaling in the developing visual cortex

Leighton

Houwen

Cheyne

et al. 2020

Preprint

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During early development, even before the senses are active, bursts of activity travel across the nervous system. This spontaneously generated activity drives the refinement of synaptic connections, preparing young networks for patterned sensory input. Synaptic fine-tuning relies not only on the presence of spontaneous activity, but also on the specific characteristics of these activity patterns, such as their frequency, amplitude and synchronicity. Here, we provide evidence that these crucial characteristics are shaped by the relative balance of excitation and inhibition, where patterns with distinct characteristics have different excitatory/inhibitory ratios. Inhibition can control whether cells participate during a spontaneous event, as pharmacogenetic suppression of the somatostatin (SST) expressing subtype of inhibitory interneurons increased cell recruitment and lateral spread of events. KeywordsMouse, in vivo, pharmacogenetics, somatostatin expressing interneuron, VIP expressing interneuron, calcium imaging, DREADD

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“…Pcdh-γ C isoforms in young cIN could also be interacting with other Pcdhs expressed by pyramidal neurons and therefore explain the adjustment in cIN number that occurs as a function of pyramidal cell number (Wong et al 2018). Recent work has shown that coordinated activity of synaptically connected assemblies of cIN and pyramidal cells is essential for the survival of MGE-derived cIN (Duan et al 2020). It is possible that all or some of the Pcdh-γ C isoforms are required for cIN of the same age to find each other and form these assemblies.…”

Section: Discussionmentioning

confidence: 99%

Clustered γ-Protocadherins Regulate Cortical Interneuron Programmed Cell Death

Mancia¹,

Spatazza²,

Rakela³

et al. 2020

Preprint

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Cortical function critically depends on inhibitory/excitatory balance. Cortical inhibitory interneurons (cINs) are born in the ventral forebrain. After completing their migration into cortex, their final numbers are adjustedduring a period of postnatal development -by programmed cell death. The mechanisms that regulate cIN elimination remains controversial. Here we show that genes in the protocadherin (Pcdh)-γ gene cluster, but not in the Pcdh-α or Pcdh-β clusters, are required for the survival of cINs through a BAX-dependent mechanism. Surprisingly, the physiological and morphological properties of Pcdh-γ deficient and wild type cINs during cIN cell death were indistinguishable. Co-transplantation of wild type and Pcdh-γ deficient interneuron precursor cells demonstrate that: 1) the number of mutant cINs eliminated was much higher than that of wild type cells, but the proportion of mutant or WT cells undergoing cell death was not affected by their density; 2) the presence of mutant cINs increases cell death among wild-type counterparts, and 3) cIN survival is dependent on the expression of Pcdh-γ C3, C4, and C5. We conclude that Pcdh-γ, and specifically γC3, γC4, and γC5, play a critical role in regulating cIN survival during the endogenous period of programmed cIN death. SignificanceInhibitory cortical interneurons (cIN) in the cerebral cortex originate from the ventral embryonic forebrain. After a long migration, they come together with local excitatory neurons to form cortical circuits. These circuits are responsible for higher brain functions, and the improper balance of excitation/inhibition in the cortex can result in mental diseases. Therefore, an understanding of how the final number of cINs is determined is both biologically and, likely, therapeutically significant. Here we show that cell surface homophilic binding proteins belonging to the clustered protocadherin gene family, specifically three isoforms in the Pcdh-γ cluster, play a key role in the regulation cIN programmed cell death. Co-transplantation of mutant and wild-type cINs shows that Pcdh-γ genes have cell-autonomous and non-cell autonomous roles in the regulation of cIN cell death. This work will help identify the molecular mechanisms and cell-cell interactions that determine how the proper ratio of excitatory to inhibitory neurons is determined in the cerebral cortex.

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GABAergic Restriction of Network Dynamics Regulates Interneuron Survival in the Developing Cortex

Cited by 81 publications

References 83 publications

Shifting Developmental Trajectories During Critical Periods of Brain Formation

Shifting Developmental Trajectories During Critical Periods of Brain Formation

Control of spontaneous activity patterns by inhibitory signaling in the developing visual cortex

Clustered γ-Protocadherins Regulate Cortical Interneuron Programmed Cell Death

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