Mapping of neuron soma size as an effective approach to delineate differences between neural populations

Lingley, Alexander J.; Bowdridge, Joshua C.; Farivar, Reza; Duffy, Kevin R.

doi:10.1016/j.jneumeth.2018.04.018

Cited by 4 publications

(3 citation statements)

References 27 publications

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“…Several morphometric studies have shown a reduction in neuronal size in the neocortex of patients with ASD 27 . We used the approach which has been developed by Lingley et al to specifically map neuronal soma size to identify the differences between neuronal cell populations 28 . By applying the same color code and by ranging neurons within the same size categories, we were able to evaluate the distribution of the soma size of human grafted CTR and ASD neurons within the host cortex.…”

Section: Discussionmentioning

confidence: 99%

A chimeric mouse model to study human iPSC-derived neurons: the case of a truncating SHANK3 mutation

Vitrac

Pons

Balkota

et al. 2020

Sci Rep

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Using human induced pluripotent stem cells (ipSc), recent studies have shown that the events underlying autism spectrum disorders (ASD) can occur during neonatal development. We previously analyzed the ipSc-derived pyramidal cortical neurons of a subset of patients with ASD carrying de novo heterozygous mutations in postsynaptic SHANK3 protein, in culture. We reported altered spinogenesis of those neurons. the transplantation of human ipSc-derived neuronal precursors into mouse brain represents a novel option for in vivo analysis of mutations affecting the human brain. in this study, we transplanted the neuronal precursor cells (npc) into the cortex of newborn mice to analyze their integration and maturation at early stages of development and studied axonal projections of transplanted human neurons into adult mouse brain. We then co-transplanted npc from a control individual and from a patient carrying a de novo heterozygous SHANK3 mutation. We observed a reduction in cell soma size of selective neuronal categories and in axonal projections at 30 days post-transplantation. In contrast to previous in vitro studies, we did not observe any alteration in spinogenesis at this early age. The humanized chimeric mouse models offer the means to analyze ASD-associated mutations further and provide the opportunity to visualize phenotypes in vivo. The use of human-derived cellular models to study neurodevelopmental disorders such as autism spectrum disorders (ASD) is an appropriate approach to link causal genetic alterations to molecular mechanisms that may occur in humans during pre-and postnatal brain development. The "SH3 and multiple ankyrin repeat domain 3" (SHANK3) is a member of the SHANK gene family located on chromosome 22 in humans which contains multiple structural domains as we previously demonstrated by homology modeling 1. Mutations in SHANK3 represent some of the best-known genetic causes for ASD and account for the severe intellectual deficiency (ID) and language deficits observed in 1-2% of patients with ASD 2,3. SHANK3 haploinsufficiency also contributes to the clinical symptoms of patients with Phelan-McDermid syndrome which presents a deletion of chromosome 22q13 that includes SHANK3 in the large majority of cases 4,5. SHANK3 is a critical partner of a major signaling complex expressed at postsynaptic densities (PSD) of glutamatergic synapses which involves cytoskeletal networks at both the soma and the neurites of neuronal cells 6. SHANK3 therefore plays a crucial role in synapse formation and dendritic spine maturation. The fundamental role of SHANK3 at such excitatory synapses was initially investigated by using genetically modified mouse models 7-9 , or by overexpressing mutated SHANK3 protein in transfected rat neurons in culture 10. Human induced pluripotent stem cells (iPSC)-derived neurons represent a valuable model for in vitro analysis of SHANK3 deficiencies in humans 11-15. Accordingly, we recently selected four independent patients with heterozygous truncating de novo SHANK3 point mutations wh...

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Section: Discussionmentioning

confidence: 99%

A chimeric mouse model to study human iPSC-derived neurons: the case of a truncating SHANK3 mutation

Vitrac

Pons

Balkota

et al. 2020

Sci Rep

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“…Type I cells are a class of electrically excitable cells that depolarise when exposed to stimuli and have been described as “ essentially neuron-like in [their] properties ” ( Duchen et al, 1988 ). Neurons of the CNS are also a widely heterogeneous population that are physically rather distinct to type I cells particularly with respect to size, with the majority of neuronal soma ranging between 20 to 70 μm ( Lingley et al, 2018 ). Like type I cells, neurons depolarise to stimuli.…”

Section: Cellular and Molecular Similarities Between The Carotid Body...mentioning

confidence: 99%

Cellular basis of learning and memory in the carotid body

Gold

Bardsley²,

Ponnampalam³

et al. 2022

Front. Synaptic Neurosci.

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The carotid body is the primary peripheral chemoreceptor in the body, and critical for respiration and cardiovascular adjustments during hypoxia. Yet considerable evidence now implicates the carotid body as a multimodal sensor, mediating the chemoreflexes of a wide range of physiological responses, including pH, temperature, and acidosis as well as hormonal, glucose and immune regulation. How does the carotid body detect and initiate appropriate physiological responses for these diverse stimuli? The answer to this may lie in the structure of the carotid body itself. We suggest that at an organ-level the carotid body is comparable to a miniature brain with compartmentalized discrete regions of clustered glomus cells defined by their neurotransmitter expression and receptor profiles, and with connectivity to defined reflex arcs that play a key role in initiating distinct physiological responses, similar in many ways to a switchboard that connects specific inputs to selective outputs. Similarly, within the central nervous system, specific physiological outcomes are co-ordinated, through signaling via distinct neuronal connectivity. As with the brain, we propose that highly organized cellular connectivity is critical for mediating co-ordinated outputs from the carotid body to a given stimulus. Moreover, it appears that the rudimentary components for synaptic plasticity, and learning and memory are conserved in the carotid body including the presence of glutamate and GABAergic systems, where evidence pinpoints that pathophysiology of common diseases of the carotid body may be linked to deviations in these processes. Several decades of research have contributed to our understanding of the central nervous system in health and disease, and we discuss that understanding the key processes involved in neuronal dysfunction and synaptic activity may be translated to the carotid body, offering new insights and avenues for therapeutic innovation.

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“…Highly metabolic brain regions usually show high expression of COX activity in histochemical assays and vice versa (Mendelez-Ferro et al, 2013). For instance, COX histochemistry helped to understand the functional organization of parallel visual pathways in primates (Peres et al, 2019), and provided evidence for delineating boundaries of cortical neurons in layers and areas (Balaram, Young & Kaas, 2014), and allowed identification of human visual area 1 (V1) cortical areas related to processing of information from the left and the right eyes (Lingley et al, 2018). Furthermore, COX marking helped to reveal that the primate second-order visual area (V2) shows compartmental organization based on bands that run orthogonal to the limits between V1 and V2 (Wong-Riley & Carroll, 1984;DeYoe & Van Essen, 1985;Zeki & Shipp, 1989;Gattass et al, 1990).…”

Section: Possible Neural Changes Associated With Generation Of Predic...mentioning

confidence: 99%

Neurofisiologia da predição baseada em memórias sobre regularidades passadas

Silva¹

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Mapping of neuron soma size as an effective approach to delineate differences between neural populations

Cited by 4 publications

References 27 publications

A chimeric mouse model to study human iPSC-derived neurons: the case of a truncating SHANK3 mutation

A chimeric mouse model to study human iPSC-derived neurons: the case of a truncating SHANK3 mutation

Cellular basis of learning and memory in the carotid body

Neurofisiologia da predição baseada em memórias sobre regularidades passadas

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