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Developmental Neurobiology

Laura Gerosa, Maura Francolini, Silvia Bassani, Maria Passafaro
PCDH19 is considered one of the most clinically relevant gene in epilepsy, second only to SCN1A. To date about 150 mutations have been identified as causative for PCDH19-female epilepsy (also known as early infantile epileptic encephalopathy-9, EIEE9), which is characterized by early onset epilepsy, intellectual disabilities and behavioral disturbances. Although little is known about the physiological role of PCDH19 and the pathogenic mechanisms that lead to EIEE9, in this review, we will present latest researches focused on these aspects, underlining protein expression, its known functions and the mechanisms by which the protein acts with particular interest in PCDH19 extracellular and intracellular neuronal roles...
November 15, 2018: Developmental Neurobiology
Cory Chew, Brandon J Kiley, Dale R Sengelaub
Partial depletion of spinal motoneuron populations induces dendritic atrophy in neighboring motoneurons, and treatment with testosterone protects motoneurons from induced dendritic atrophy. We explored a potential mechanism for this induced atrophy and protection by testosterone, examining the microglial response to partial depletion of motoneurons. Motoneurons innervating the vastus medialis muscles of adult male rats were killed by intramuscular injection of cholera toxin-conjugated saporin; some saporin-injected rats were treated with testosterone...
November 14, 2018: Developmental Neurobiology
Yan Chu Chen, Yu-Wei Chang, Yi-Shuian Huang
Regulated local translation - whereby specific mRNAs are transported and localized in subcellular domains where they are translated in response to regional signals - allows for remote control of gene expression to concentrate proteins in subcellular compartments. Neurons are highly polarized cells with unique features favoring local control for axonal pathfinding and synaptic plasticity, which are key processes involved in constructing functional circuits in the developing brain. Neurodevelopmental disorders are caused by genetic or environmental factors that disturb the nervous system development during prenatal and early childhood periods...
November 14, 2018: Developmental Neurobiology
Wenlin Liao
Rett syndrome (RTT) is a monogenic neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. Patients with RTT develop symptoms after 6-18 months of age, exhibiting characteristic movement deficits, such as ambulatory difficulties and loss of hand skills, in addition to breathing abnormalities and intellectual disability. Given the striking psychomotor dysfunction, numerous studies have investigated the underlying neurochemical and circuit mechanisms from different aspects...
November 14, 2018: Developmental Neurobiology
William M Trask, Mufaddal I Baghdadwala, Richard J A Wilson
Many vital motor behaviors-including locomotion, swallowing, and breathing-appear to be dependent upon the activity of and coordination between multiple endogenously rhythmogenic nuclei, or neural oscillators. Much as the functional development of sensory circuits is shaped during maturation, we hypothesized that coordination of oscillators involved in motor control may likewise be maturation-dependent; i.e., coupling and coordination between oscillators changes over development. We tested this hypothesis using the bullfrog isolated brainstem preparation to study the metamorphic transition of ventilatory motor patterns from early rhythmic buccal (water) ventilation in the tadpole to the mature pattern of rhythmic buccal and lung (air) ventilation in the adult...
October 24, 2018: Developmental Neurobiology
Lisa C Hiura, Aubrey M Kelly, Alexander G Ophir
The social needs of organisms change as they mature. Yet, little is known about the mechanisms that subserve processing social interactions or how these systems develop. The medial extended amygdala (meEA) is comprised of the medial bed nucleus of the stria terminalis (BSTm) and the medial amygdala (MeA). This neural complex holds great promise for understanding how the social brain processes information. We assessed expression of the immediate early gene cFos and the enzyme tyrosine hydroxylase (TH) at three developmental time-points (postnatal day [PND] 2, 9, and 21) to determine how developing prairie voles process familial social contact, separation, and reunion...
October 24, 2018: Developmental Neurobiology
Beryl Y T Chung, Craig D C Bailey
The hippocampal formation (HF) plays an important role to facilitate higher-order cognitive functions. Cholinergic activation of heteromeric nicotinic acetylcholine receptors (nAChRs) within the HF is critical for the normal development of principal neurons within this brain region. However, previous research investigating the expression and function of heteromeric nAChRs in principal neurons of the HF is limited to males or does not differentiate between sexes. We used whole-cell electrophysiology to show that principal neurons in the CA1 region of the female mouse HF are excited by heteromeric nAChRs throughout postnatal development, with the greatest response occurring during the first two weeks of postnatal life...
October 24, 2018: Developmental Neurobiology
Xiaokuang Ma, Ke Chen, Zhongming Lu, Mariel Piechowicz, Qiang Liu, Jie Wu, Shenfeng Qiu
As more genes conferring risks to neurodevelopmental disorders are identified, translating these genetic risk factors into biological mechanisms that impact the trajectory of the developing brain is a critical next step. Here we report that disrupted signaling mediated MET receptor tyrosine kinase (RTK), an established risk factor for autism spectrum disorders (ASD), in the developing hippocampus glutamatergic circuit leads to profound deficits in neural development, synaptic transmission and plasticity. In cultured hippocampus slices prepared from neonatal mice, pharmacological inhibition of MET kinase activity suppresses dendritic arborization and disrupts normal dendritic spine development...
October 10, 2018: Developmental Neurobiology
Xuting Shen, Hoi Ting Yeung, Kwok-On Lai
Synapses are the basic structural and functional units for information processing and storage in the brain. Their diverse properties and functions ultimately underlie the complexity of human behavior. Proper development and maintenance of synapses are essential for normal functioning of the nervous system. Disruption in synaptogenesis and the consequent alteration in synaptic function have been strongly implicated to cause neurodevelopmental disorders such as autism spectrum disorders (ASDs) and schizophrenia (SCZ)...
October 10, 2018: Developmental Neurobiology
David L Stocum
Nerves, in conjunction with the apical epidermal cap (AEC), play an important role in the proliferation of the mesenchymal progenitor cells comprising the blastema of regenerating urodele amphibian limbs. Reinnervation after amputation requires factors supplied by the forming blastema, and neurotrophic factors must be present at or above a quantitative threshold for mitosis of the blastema cells. The AEC forms independently of nerves, but requires nerves to be maintained. Urodele limb buds are independent of nerves for regeneration, but innervation imposes a regenerative requirement for nerve factors on their cells as they differentiate...
October 10, 2018: Developmental Neurobiology
Zhisheng Ji, Guowei Zhang, Li Chen, Jiong Li, Yuhao Yang, Caihui Cha, Jifeng Zhang, Hongsheng Lin, Guoqing Guo
Changing microtubule dynamics is sufficient to alter axon and dendrite specification and development. Spastin participates in the growth and regeneration of neurites by severing microtubules into small segments, and collapsin response mediator protein 5 (CRMP5) provides structural support and serves as a track for cargo transport by promoting microtubule polymerization. Nevertheless, how spastin and CRMP5 cooperate to regulate neurite outgrowth by controlling microtubule dynamics needs to be elucidated. In our present study, spastin interacted with CRMP5 in vitro and in vivo...
September 26, 2018: Developmental Neurobiology
Nicole A Guitar, David F Sherry
Adult hippocampal neurogenesis has been proposed to both aid memory formation and disrupt memory. We examined the role of adult hippocampal neurogenesis in spatial working and reference memory in black-capped chickadees (Poecile atricapillus), a passerine bird that relies on spatial memory for cache retrieval and foraging. We tested spatial working and spatial reference memory in birds that had received methylazoxymethanol acetate (MAM), a neurotoxin that decreases hippocampal neurogenesis. MAM treatment significantly reduced neurogenesis in the hippocampus quantified by doublecortin (DCX) labeling of newly divided and migrating neurons...
September 24, 2018: Developmental Neurobiology
Yong-Chuan Zhu, Zhi-Qi Xiong
The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) encodes a serine/threonine kinase abundantly expressed in the brain. Mutations in CDKL5 have been associated with neurodevelopmental disorders characterized by early-onset epileptic encephalopathy and severe intellectual disability, suggesting that CDKL5 plays important roles in brain development and function. Recent studies using cultured neurons, knockout mice, and human iPSC-derived neurons have demonstrated that CDKL5 regulates axon outgrowth, dendritic morphogenesis and synapse formation...
September 24, 2018: Developmental Neurobiology
Zhenyu Liu, Amit Thakar, Stephen W Santoro, Kara G Pratt
As the catalytic component of γ-secretase, presenilin (PS) has long been studied in the context of Alzheimer's disease through cleaving the amyloid precursor protein. PS/γ-secretase, however, also cleaves a multitude of single-pass transmembrane proteins that are important during development, including Notch, the netrin receptor DCC, cadherins, drebrin-A, and the EphB2 receptor. Because transgenic PS-KO mice do not survive to birth, studies of this molecule during later embryonic or early postnatal stages of development have been carried out using cell cultures or conditional knock-out mice, respectively...
September 24, 2018: Developmental Neurobiology
Kaci L Pickett, Paxton S Stein, Michael A Vincen-Brown, Jason Q Pilarski
The medullary portion of the embryonic zebra finch hindbrain was isolated and superfused with physiologically relevant artificial cerebral spinal fluid. This in vitro preparation produced uninterrupted rhythmic episodes of neural activity via cranial nerve IX (glossopharyngeal) from embryonic day 4 (E4) through hatching on E14. Cranial nerve IX carries motor activity to the glottis during the inspiratory phase of breathing, and we focused on the role of synaptic inhibition during the embryonic and perinatal maturation of this branchiomotor outflow...
November 2018: Developmental Neurobiology
Jillian Mei-Ling Liu, Summer Rose Fair, Behiye Kaya, Jessica Nabile Zuniga, Hasnaa Rashad Mostafa, Michele Joana Alves, Julie A Stephens, Mikayla Jones, M Tahir Aslan, Catherine Czeisler, José Javier Otero
The emergence of systems neuroscience tools requires parallel generation of objective analytical workflows for experimental neuropathology. We developed an objective analytical workflow that we used to determine how specific autonomic neural lineages change during postnatal development. While a wealth of knowledge exists regarding postnatal alterations in respiratory neural function, how these neural circuits change and develop in the weeks following birth remains less clear. In this study, we developed our workflow by combining genetic mouse modeling and quantitative immunofluorescent confocal microscopy and used this to examine the postnatal development of neural circuits derived from the transcription factors NKX2...
November 2018: Developmental Neurobiology
Ashley N Brandebura, Michael Morehead, Daniel T Heller, Paul Holcomb, Douglas R Kolson, Garrett Jones, Peter H Mathers, George A Spirou
Neural circuit formation involves maturation of neuronal, glial and vascular cells, as well as cell proliferation and cell death. A fundamental understanding of cellular mechanisms is enhanced by quantification of cell types during key events in synapse formation and pruning and possessing qualified genetic tools for cell type-specific manipulation. Acquiring this information in turn requires validated cell markers and genetic tools. We quantified changing proportions of neurons, astrocytes, oligodendrocytes, and microglia in the medial nucleus of the trapezoid body (MNTB) during neural circuit development...
November 2018: Developmental Neurobiology
Shivani C Kharod, Brandon M Carter, Shilpa D Kadam
Neonatal seizures are harmful to the developing brain and are associated with mortality and long-term neurological comorbidities. Hypoxic-ischemic encephalopathy (HIE) seizures represent a significant proportion of such seizures. Phenobarbital (PB) remains the first line anti-seizure drug (ASD) treatment but fails ~50% of the time. Translational models of neonatal seizures are crucial to investigating mechanisms underlying PB-resistance. A model of PB-resistant ischemic seizures in postnatal day 7 (P7) CD-1 mice reported K-Cl cotransporter 2 (KCC2) degradation that has been shown to be due to activation of the TrkB pathway...
November 2018: Developmental Neurobiology
Paige M Dingess, Amit Thakar, Zhaojie Zhang, Francis W Flynn, Travis E Brown
Excess consumption of dietary sodium during pregnancy has been shown to impair offspring cardiovascular function and enhance salt preference in adulthood, but little is known regarding the long-term impact of this nutritional surplus on offspring brain morphology and behavior. Using a combination of cellular and behavioral approaches, we examined the impact of maternal salt intake during the perinatal period on structural plasticity in the prefrontal cortex (PFC) and nucleus accumbens (NAc) in weanling and adult offspring as well as reward- and stress-driven behaviors in adult offspring...
November 2018: Developmental Neurobiology
Bartosz Caban, Agata Staszelis, Paulina Kazmierska, Tomasz Kowalczyk, Jan Konopacki
Theta rhythms have been recorded from rat brain slices of the posterior hypothalamic area (PHa), including the supramammillary and posterior hypothalamic nuclei. Additionally, in numerous studies theta-related neurons were identified in the PHa according to the classification of Bland and Colom (Progress in Neurobiology, 41, 157-208, 1993). It is currently widely accepted that the PHa contributes to the process of HPC theta frequency programming at least in certain behavioral states. The postnatal development of the HPC and its ability to generate theta has also been a subject of studies...
November 2018: Developmental Neurobiology
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