scholarly journals miR-128 regulates neuronal migration, outgrowth and intrinsic excitability via the intellectual disability gene Phf6

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Eleonora Franzoni ◽  
Sam A Booker ◽  
Srinivas Parthasarathy ◽  
Frederick Rehfeld ◽  
Sabine Grosser ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Deleterious Effect ◽  
Adult Stem Cell ◽  
Cognitive Disorder ◽  
Neuronal Morphology ◽  
Intrinsic Excitability ◽  
Electrophysiological Properties ◽  
Physiological Properties ◽  
Stem Cell Niches ◽  
Cortical Lamination

miR-128, a brain-enriched microRNA, has been implicated in the control of neurogenesis and synaptogenesis but its potential roles in intervening processes have not been addressed. We show that post-transcriptional mechanisms restrict miR-128 accumulation to post-mitotic neurons during mouse corticogenesis and in adult stem cell niches. Whereas premature miR-128 expression in progenitors for upper layer neurons leads to impaired neuronal migration and inappropriate branching, sponge-mediated inhibition results in overmigration. Within the upper layers, premature miR-128 expression reduces the complexity of dendritic arborization, associated with altered electrophysiological properties. We show that Phf6, a gene mutated in the cognitive disorder Börjeson-Forssman-Lehmann syndrome, is an important regulatory target for miR-128. Restoring PHF6 expression counteracts the deleterious effect of miR-128 on neuronal migration, outgrowth and intrinsic physiological properties. Our results place miR-128 upstream of PHF6 in a pathway vital for cortical lamination as well as for the development of neuronal morphology and intrinsic excitability.

scholarly journals Heterogeneities in intrinsic excitability and frequency-dependent response properties of granule cells across the blades of the rat dentate gyrus

2019 ◽  
Author(s):  
Poonam Mishra ◽  
Rishikesh Narayanan
Keyword(s):  
Dentate Gyrus ◽  
Temporal Summation ◽  
Granule Cells ◽  
Neuronal Morphology ◽  
Intrinsic Excitability ◽  
Activity Levels ◽  
Frequency Dependent ◽  
Information Encoding ◽  
Response Properties ◽  
Electrophysiological Properties

ABSTRACTThe dentate gyrus (DG), the input gate to the hippocampus proper, is anatomically segregated into three different sectors, namely the suprapyramidal blade, the crest region and the infrapyramidal blade. Although there are well-established differences between these sectors in terms of neuronal morphology, connectivity patterns and activity levels, differences in electrophysiological properties of granule cells within these sectors have remained unexplored. Here, employing somatic whole-cell patch-clamp recordings from the rat DG, we demonstrate that granule cells in these sectors manifest considerable heterogeneities in their intrinsic excitability, temporal summation, action potential characteristics and frequency-dependent response properties. Across sectors, these neurons showed positive temporal summation of their responses to inputs mimicking excitatory postsynaptic currents, and showed little to no sag in their voltage responses to pulse currents. Consistently, the impedance amplitude profile manifested low-pass characteristics and the impedance phase profile lacked positive phase values at all measured frequencies, voltages and for all sectors. Granule cells in all sectors exhibited class I excitability, with broadly linear firing rate profiles, and granule cells in the crest region fired significantly less action potentials compared to those in the infrapyramidal blade. Finally, we found weak pairwise correlations across the 18 different measurements obtained individually from each of the three sectors, providing evidence that these measurements are indeed reporting distinct aspects of neuronal physiology. Together, our analyses show that granule cells act as integrators of afferent information, and emphasize the need to account for the considerable physiological heterogeneities in assessing their roles in information encoding and processing.

scholarly journals Neuronal Migration Generates New Populations of Neurons That Develop Unique Connections, Physiological Properties and Pathologies

2019 ◽  
Vol 7 ◽  
Author(s):  
Bernd Fritzsch ◽  
Karen L. Elliott ◽  
Gabriela Pavlinkova ◽  
Jeremy S. Duncan ◽  
Marlan R. Hansen ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Physiological Properties

scholarly journals The SH2 domain is crucial for function of Fyn in neuronal migration and cortical lamination

BMB Reports ◽  
2015 ◽  
Vol 48 (2) ◽  
pp. 97-102 ◽  
Author(s):  
Xi Lu ◽  
Xinde Hu ◽  
Lingzhen Song ◽  
Lei An ◽  
Minghui Duan ◽  
...  
Keyword(s):  
Neuronal Migration ◽  
Sh2 Domain ◽  
Cortical Lamination

scholarly journals The intrinsic electrophysiological properties of neurons derived from mouse embryonic stem cells overexpressing neurogenin-1

2010 ◽  
Vol 299 (6) ◽  
pp. C1335-C1344 ◽  
Author(s):  
Mingjie Tong ◽  
Jeannie L. Hernandez ◽  
Erin K. Purcell ◽  
Richard A. Altschuler ◽  
R. Keith Duncan
Keyword(s):  
Stem Cells ◽  
Action Potentials ◽  
High Efficiency ◽  
Es Cells ◽  
Embryonic Stem ◽  
Neuronal Morphology ◽  
Neural Repair ◽  
Neuronal Phenotype ◽  
Electrophysiological Properties

A mouse embryonic stem (ES) cell line containing an inducible transgene for the proneural gene Neurog1 has been used to generate glutamatergic neurons at a high efficiency. The present study used in vitro electrophysiology to establish the timeline for acquiring a functional neuronal phenotype in Neurog1-induced cells exhibiting a neuronal morphology. TTX-sensitive action potentials could be evoked from over 80% of the cells after only 4.5 days in vitro (DIV). These cells uniformly showed rapidly adapting responses to current injection, firing one to three action potentials at the onset of the stimulus. In the absence of Neurog1, a limited number of ES cells adopted a neuronal morphology, but these cells displayed slow calcium depolarizations rather than sodium-based spikes. Voltage-gated Na+, K+, and Ca2+ currents were present in nearly all induced cells as early as 4.5 DIV. The voltage-dependent properties of these currents changed little from 4 to 12 DIV with half-activation voltage varying by <10 mV for any current type throughout the culture period. This study demonstrates that forced expression of proneural genes can induce ES cells to quickly acquire a functional neuronal phenotype with mature electrophysiological properties. Transient overexpression of Neurog1 may be used in neural repair strategies that require the rapid induction of functional neurons from pluripotent stem cells.

Electrophysiology of Interneurons in the Glomerular Layer of the Rat Olfactory Bulb

2001 ◽  
Vol 86 (4) ◽  
pp. 1899-1907 ◽  
Author(s):  
A. Rory McQuiston ◽  
Lawrence C. Katz
Keyword(s):  
Olfactory Bulb ◽  
Action Potentials ◽  
Neuronal Morphology ◽  
Bursting Neurons ◽  
Whole Cell Patch Clamp ◽  
Physiological Properties ◽  
Receptor Neurons ◽  
Tufted Cells ◽  
Olfactory Bulb Slices ◽  
Channel Dependent

In the mammalian olfactory bulb, glomeruli are surrounded by a heterogeneous population of interneurons called juxtaglomerular neurons. As they receive direct input from olfactory receptor neurons and connect with mitral cells, they are involved in the initial stages of olfactory information processing, but little is known about their detailed physiological properties. Using whole cell patch-clamp techniques, we recorded from juxtaglomerular neurons in rat olfactory bulb slices. Based on their response to depolarizing pulses, juxtaglomerular neurons could be divided into two physiological classes: bursting and standard firing. When depolarized, the standard firing neurons exhibited a range of responses: accommodating, nonaccommodating, irregular firing, and delayed to firing patterns of action potentials. Although the firing pattern was not rigorously predictive of a particular neuronal morphology, most short axon cells fired accommodating trains of action potentials, while most delayed to firing cells were external tufted cells. In contrast to the standard firing neurons, bursting neurons produced a calcium-channel-dependent low-threshold spike when depolarized either by current injection or by spontaneous or evoked postsynaptic potentials. Bursting neurons also could oscillate spontaneously. Most bursting cells were either periglomerular cells or external tufted cells. Based on their mode of firing and placement in the bulb circuit, these bursting cells are well situated to drive synchronous oscillations in the olfactory bulb.

scholarly journals Remodeling the Human Adult Stem Cell Niche for Regenerative Medicine Applications

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Silvana Bardelli ◽  
Marco Moccetti
Keyword(s):  
Stem Cell ◽  
Regenerative Medicine ◽  
Translational Medicine ◽  
Process Development ◽  
Therapeutic Potential ◽  
Adult Stem Cell ◽  
Cell Renewal ◽  
Stem Cell Niches

The interactions between stem cells and their surrounding microenvironment are pivotal to determine tissue homeostasis and stem cell renewal or differentiation and regenerationin vivo. Ever since they were postulated in 1978, stem cell niches have been identified and characterized in many germline and adult tissues. Comprehensive studies over the last decades helped to clarify the critical components of stem cell niches that include cellular, extracellular, biochemical, molecular, and physical regulators. This knowledge has direct impact on their inherent regenerative potential. Clinical applications demand readily available cell sources that, under controlled conditions, provide a specific therapeutic function. Thus, translational medicine aims at optimizingin vitroorin vivothe various components and complex architecture of the niche to exploit its therapeutic potential. Accordingly, the objective is to recreate the natural niche microenvironment during cell therapy process development and closely comply with the requests of regulatory authorities. In this paper, we review the most recent advances of translational medicine approaches that target the adult stem cell natural niche microenvironment for regenerative medicine applications.

Neuroendocrine bag cells of Aplysia are activated by bag cell peptide-containing neurons in the pleural ganglion

1989 ◽  
Vol 61 (6) ◽  
pp. 1142-1152 ◽  
Author(s):  
R. O. Brown ◽  
S. M. Pulst ◽  
E. Mayeri
Keyword(s):  
Lucifer Yellow ◽  
Cell Activity ◽  
Feedback Mechanism ◽  
Egg Laying ◽  
Electrophysiological Properties ◽  
Physiological Properties ◽  
Positive Feedback Mechanism ◽  
Bag Cells ◽  
Small Clusters

1. The generation of egg-laying behavior in the marine mollusk Aplysia involves a prolonged burst discharge in the neuroendocrine bag cells, which secrete neuropeptides derived from the egg-laying hormone/bag cell peptide (ELH/BCP) precursor protein. 2. Besides the bag cells, which are located in the abdominal ganglion, small clusters of neurons in the cerebral and pleural ganglia also express the ELH/BCP neuropeptides. We made intracellular recordings from 32 of these ELH/BCP cells in right pleural ganglia, in 18 preparations, to characterize their physiological properties and their functional relationship to the bag cells. 3. The identification of these ELH/BCP cells was confirmed by pressure injection of Lucifer yellow and subsequent immunocytochemical processing for alpha-BCP immunoreactivity. 4. The basic electrophysiological properties of the pleural ELH/BCP cells were similar to those of the bag cells. These pleural cells were directly demonstrated to be electrically coupled, and direct intracellular stimulation of individual pleural ELH/BCP cells initiated prolonged, synchronous burst discharges in the entire cluster through a positive feedback mechanism. 5. Burst discharges elicited in the pleural ELH/BCP cells consistently initiated burst discharges in the bag cells. Bag cell burst discharges were less effective in initiating burst discharges in the pleural ELH/BCP cells, indicating that there were reciprocal but asymmetrical connections. 6. The results show that the pleural ELH/BCP cells are functionally coupled to the bag cells. They support the hypothesis that the pleural ELH/BCP cells are part of the descending pathway that initiates bag cell activity and egg-laying behavior, in vivo.

scholarly journals Intrinsic physiological properties of the five types of mouse ganglion-cell photoreceptors

2013 ◽  
Vol 109 (7) ◽  
pp. 1876-1889 ◽  
Author(s):  
Caiping Hu ◽  
DiJon D. Hill ◽  
Kwoon Y. Wong
Keyword(s):  
Ganglion Cells ◽  
Membrane Resistance ◽  
The Other ◽  
Functional Roles ◽  
Electrophysiological Properties ◽  
Voltage Gated ◽  
Physiological Diversity ◽  
Physiological Properties ◽  
Comprehensive Survey ◽  
And Function

In the mammalian retina, some ganglion cells express the photopigment melanopsin and function as photoreceptors. Five morphological types of these intrinsically photosensitive retinal ganglion cells (ipRGCs), M1–M5, have been identified in mice. Whereas M1 specializes in non-image-forming visual functions and drives such behaviors as the pupillary light reflex and circadian photoentrainment, the other types appear to contribute to image-forming as well as non-image-forming vision. Recent work has begun to reveal physiological diversity among some of the ipRGC types, including differences in photosensitivity, firing rate, and membrane resistance. To gain further insights into these neurons' functional differences, we conducted a comprehensive survey of the electrophysiological properties of all five morphological types. Compared with the other types, M1 had the highest membrane resistance, longest membrane time constant, lowest spike frequencies, widest action potentials, most positive spike thresholds, smallest hyperpolarization-activated inwardly-rectifying current-induced “sagging” responses to hyperpolarizing currents, and the largest effects of voltage-gated K+ currents on membrane potentials. M4 and M5 were at the other end of the spectrum for most of these measures, while M2 and M3 tended to be in the middle of this spectrum. Additionally, M1 and M2 cells generated more diverse voltage-gated Ca2+ currents than M3–M5. In conclusion, M1 cells are significantly different from all other ipRGCs in most respects, possibly reflecting the unique physiological requirements of non-image-forming vision. Furthermore, the non-M1 ipRGCs are electrophysiologically heterogeneous, implicating these cells' diverse functional roles in both non-image-forming vision and pattern vision.

scholarly journals MCF2 is linked to a complex perisylvian syndrome and affects cortical lamination

2019 ◽  
Author(s):  
Aude Molinard-Chenu ◽  
Joël Fluss ◽  
Sacha Laurent ◽  
Michel Guipponi ◽  
Alexandre G Dayer
Keyword(s):  
Motor Neuron ◽  
Missense Mutation ◽  
Neuronal Migration ◽  
Cortical Neurons ◽  
In Utero ◽  
Projection Neurons ◽  
Cortical Projection ◽  
Cortical Laminar ◽  
Congenital Bilateral Perisylvian Syndrome ◽  
Cortical Lamination

AbstractThe combination of congenital bilateral perisylvian syndrome (CBPS) with lower motor neuron dysfunction is unusual and suggests a potential common genetic insult affecting basic neurodevelopmental processes. Here we identify a putatively pathogenic missense mutation in the MCF2 gene in a boy with CBPS. Using in utero electroporation to genetically manipulate cortical neurons during corticogenesis, we demonstrate that the mouse Mcf2 gene controls the embryonic migration of cortical projection neurons. Strikingly, we find that the CBPS-associated MCF2 mutation impairs cortical laminar positioning, supporting the hypothesis that alterations in the process of embryonic neuronal migration can lead to rare cases of CBPS.

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