scholarly journals Smoothened receptor signaling regulates the developmental shift of GABA polarity in rat somatosensory cortex

2020 ◽  
Vol 133 (20) ◽  
pp. jcs247700
Author(s):  
Quentin Delmotte ◽  
Mira Hamze ◽  
Igor Medina ◽  
Emmanuelle Buhler ◽  
Jinwei Zhang ◽  
...  

ABSTRACTSonic hedgehog (Shh) and its patched–smoothened receptor complex control a variety of functions in the developing central nervous system, such as neural cell proliferation and differentiation. Recently, Shh signaling components have been found to be expressed at the synaptic level in the postnatal brain, suggesting a potential role in the regulation of synaptic transmission. Using in utero electroporation of constitutively active and negative-phenotype forms of the Shh signal transducer smoothened (Smo), we studied the role of Smo signaling in the development and maturation of GABAergic transmission in the somatosensory cortex. Our results show that enhancing Smo activity during development accelerates the shift from depolarizing to hyperpolarizing GABA in a manner dependent on functional expression of potassium–chloride cotransporter type 2 (KCC2, also known as SLC12A5). On the other hand, blocking Smo activity maintains the GABA response in a depolarizing state in mature cortical neurons, resulting in altered chloride homeostasis and increased seizure susceptibility. This study reveals unexpected functions of Smo signaling in the regulation of chloride homeostasis, through control of KCC2 cell-surface stability, and the timing of the GABA excitatory-to-inhibitory shift in brain maturation.

2019 ◽  
Author(s):  
Quentin Delmotte ◽  
Igor Medina ◽  
Mira Hamze ◽  
Emmanuelle Buhler ◽  
Jinwei Zhang ◽  
...  

ABSTRACTSonic Hedgehog (Shh) and its patched-smoothened receptor complex control a variety of functions in the developing central nervous system (CNS) such as neural cell proliferation and differentiation. Recently, Shh signaling components have been found to be expressed at the synaptic level in the postnatal brain, suggesting a potential role in the regulation of synaptic transmission. Using in utero electroporation of constitutively active and dominant-negative forms of the Shh co-receptor smoothened (Smo), we studied the role of Smo signaling in the development and maturation of GABAergic transmission in the somatosensory cortex. Our results show that enhancing Smo activity during development accelerates the shift from depolarizing to hyperpolarizing GABA in dependence on functional expression of potassium-chloride cotransporter type 2 (KCC2). On the other hand, blocking Smo activity maintains GABA response in a depolarizing state in mature cortical neurons resulting in altered chloride homeostasis and increased seizure susceptibility. This study reveals an unexpected function of Smo signaling on the regulation of chloride homeostasis through the control of KCC2 cell surface stability and on the timing of the GABA inhibitory/excitatory shift in brain maturation.Summary statementThe smoothened receptor controls the time course of inhibitory transmission through the stability of the potassium-chloride cotransporter type 2 at the plasma membrane.


2016 ◽  
Vol 102 ◽  
pp. 77-85 ◽  
Author(s):  
Elisa Castagnola ◽  
Marco Marrani ◽  
Emma Maggiolini ◽  
Francesco Maita ◽  
Luca Pazzini ◽  
...  

Electrocorticography (ECoG) is receiving growing attention for both clinical and research applications thanks to its reduced invasiveness and ability of addressing large cortical areas. These benefits come with a main drawback, i.e. a limited frequency bandwidth. However, recent studies have shown that spiking activity from cortical neurons can be recorded when the ECoG grids present the following combined properties: (I) conformable substrate, (II) small neuron-sized electrodes with (III) low-impedance interfaces. We introduce here an ad-hoc designed ECoG device for investigating how electrode size, interface material composition and electrochemical properties affect the capability to record evoked and spontaneous neural signals from the rat somatosensory cortex and influence the ability to record high frequency neural signal components.Contact diameter reduction down to 8 μm was possible thanks to a specific coating of a (3,4-ethylenedioxytiophene)-poly (styrenesulfonate)-poly-(ethyleneglycol) (PEDOT-PSS-PEG) composite that drastically reduces impedance and increases electrical and ionic conductivities. In addition, the extreme thinness of the polyimide substrate (6 - 8 μm) and the presence of multiple perforations through the device ensure an effective contact with the brain surface and the free flow of cerebrospinal fluid. In-vivo validation was performed on rat somatosensory cortex.


2003 ◽  
Vol 89 (3) ◽  
pp. 1702-1712 ◽  
Author(s):  
Susan A. Masino

The profile of activity across rat somatosensory cortex on stimulation of a single whisker was examined using both intrinsic signal imaging and electrophysiological recording. In the same animals, under sodium pentobarbital anesthesia, the intrinsic signal response to a 5-Hz stimulation of whisker C2 was recorded through a thinned skull. Subsequently, the thinned skull was removed, and individual cortical neurons were recorded at multiple locations and in all cortical layers in response to the same whisker stimulation paradigm. The amplitude of the evoked response obtained with both techniques was quantified across the cortical surface with respect to distance (≤1.6 mm) from the peak intrinsic signal activity. Cortical neurons were rated as having a significant or nonsignificant whisker-evoked response as compared with a baseline period of spontaneous firing; a minority of neurons exhibited a small but significant increase in neuronal spiking even at long distances (>1.6 mm) from the optically determined peak of activity. Overall, this analysis shows a significant correlation between the two techniques in terms of the profile of evoked activity across the cortical surface. Furthermore, this data set affords a detailed and quantitative comparison between the two activity-dependent techniques—one measuring an intrinsic decrease in light reflectance based largely on metabolic changes and one measuring neuronal firing patterns. Studies such as this, comparing directly between imaging and detailed electrophysiology, may influence the interpretation of the extent of the activated area as assessed with in vivo functional imaging techniques.


2005 ◽  
Vol 25 (1_suppl) ◽  
pp. S186-S186
Author(s):  
Peter Herman ◽  
Shaun A Wahab ◽  
Andras Eke ◽  
Fahmeed Hyder

2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.   


2020 ◽  
Vol 22 (1) ◽  
pp. 168-175 ◽  
Author(s):  
Lin-Jun Sun ◽  
Chong Li ◽  
Xiang-hao Wen ◽  
Lu Guo ◽  
Zi-Fen Guo ◽  
...  

Background:: Icariin (ICA), one of the main effective components isolated from the traditional Chinese herb Epimedium brevicornu Maxim., has been reported to possess extensive pharmacological actions, including enhanced sexual function, immune regulation, anti-inflammation, and antiosteoporosis. Methods:: Our study was designed to investigate the effect of ICA on cell proliferation and differentiation and the molecular mechanism of OPG/RANKL mediated by the Estrogen Receptor (ER) in hFOB1.19 human osteoblast cells. Results:: The experimental results show that ICA can stimulate cell proliferation and increase the activity of Alkaline Phosphatase (ALP), Osteocalcin (BGP) and I Collagen (Col I) and a number of calcified nodules. Furthermore, the mRNA and protein expression of OPG and RANKL and the OPG/ RANKL mRNA and protein expression ratios were upregulated by ICA. The above-mentioned results indicated that the optimal concentration of ICA for stimulating osteogenesis was 50ng/mL. Subsequent mechanistic studies comparing 50ng/mL ICA with an estrogen receptor antagonist demonstrated that the effect of the upregulated expression is connected with the estrogen receptor. In conclusion, ICA can regulate bone formation by promoting cell proliferation and differentiation and upregulating the OPG/RANKL expression ratio by the ER in hFOB1.19 human osteoblast cells.


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