scholarly journals Cell-Type Specificity of Neuronal Excitability and Morphology in the Central Amygdala

eNeuro ◽  
2020 ◽  
pp. ENEURO.0402-20.2020
Author(s):  
Anisha P. Adke ◽  
Aleisha Khan ◽  
Hye-Sook Ahn ◽  
Jordan J. Becker ◽  
Torri D. Wilson ◽  
...  
2019 ◽  
Author(s):  
Anisha P. Adke ◽  
Aleisha Khan ◽  
Hye-Sook Ahn ◽  
Jordan J. Becker ◽  
Torri D. Wilson ◽  
...  

ABSTRACTCentral amygdala (CeA) neurons expressing protein kinase C delta (PKCδ+) or Somatostatin (Som+) differentially modulate diverse behaviors. The underlying features supporting cell-type-specific function in the CeA, however, remain unknown. Using whole-cell patch-clamp electrophysiology in acute mouse brain slices and biocytin-based neuronal reconstructions, we demonstrate that neuronal morphology and relative excitability are two distinguishing features between Som+ and PKCδ+ CeLC neurons. Som+ neurons, for example, are more excitable, compact and with more complex dendritic arborizations than PKCδ+ neurons. Cell size, intrinsic membrane properties, and anatomical localization were further shown to correlate with cell-type-specific differences in excitability. Lastly, in the context of neuropathic pain, we show a shift in the excitability equilibrium between PKCδ+ and Som+ neurons, suggesting that imbalances in the relative output of these cells underlie maladaptive changes in behaviors. Together, our results identify fundamentally important distinguishing features of PKCδ+ and Som+ cells that support cell-type-specific function in the CeA.


2021 ◽  
Author(s):  
Antonio Torres-Méndez ◽  
Sinziana Pop ◽  
Sophie Bonnal ◽  
Isabel Almudi ◽  
Alida Avola ◽  
...  

SummaryNeurons draw on alternative splicing for their increased transcriptomic complexity throughout animal phylogeny. To delve into the mechanisms controlling the assembly and evolution of this regulatory layer, we characterized the neuronal microexon program in Drosophila and compared it with that of mammals. We found that in Drosophila, this splicing program is restricted to neurons by the post-transcriptional processing of the enhancer of microexons (eMIC) domain in Srrm234 by Elav and Fne. eMIC deficiency or misexpression leads to widespread neurological alterations largely emerging from impaired neuronal activity, as revealed by a combination of neuronal imaging experiments and cell-type-specific rescues. These defects are associated with the genome-wide skipping of short neural exons, which are strongly enriched in ion channels. Remarkably, we found no overlap of eMIC-regulated exons between flies and mice, illustrating how ancient post-transcriptional programs can evolve independently in different phyla to impact distinct cellular modules while maintaining cell-type specificity.


2007 ◽  
Vol 19 (8) ◽  
pp. 2624-2635 ◽  
Author(s):  
Yuko Nakagawa ◽  
Hideki Hanaoka ◽  
Masaharu Kobayashi ◽  
Kazumaru Miyoshi ◽  
Kyoko Miwa ◽  
...  

2006 ◽  
Vol 26 (22) ◽  
pp. 8515-8526 ◽  
Author(s):  
Judith Jans ◽  
George A. Garinis ◽  
Wouter Schul ◽  
Adri van Oudenaren ◽  
Michael Moorhouse ◽  
...  

ABSTRACT Cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts (6-4PPs) comprise major UV-induced photolesions. If left unrepaired, these lesions can induce mutations and skin cancer, which is facilitated by UV-induced immunosuppression. Yet the contribution of lesion and cell type specificity to the harmful biological effects of UV exposure remains currently unclear. Using a series of photolyase-transgenic mice to ubiquitously remove either CPDs or 6-4PPs from all cells in the mouse skin or selectively from basal keratinocytes, we show that the majority of UV-induced acute effects to require the presence of CPDs in basal keratinocytes in the mouse skin. At the fundamental level of gene expression, CPDs induce the expression of genes associated with repair and recombinational processing of DNA damage, as well as apoptosis and a response to stress. At the organismal level, photolyase-mediated removal of CPDs, but not 6-4PPs, from the genome of only basal keratinocytes substantially diminishes the incidence of skin tumors; however, it does not affect the UVB-mediated immunosuppression. Taken together, these findings reveal a differential role of basal keratinocytes in these processes, providing novel insights into the skin's acute and chronic responses to UV in a lesion- and cell-type-specific manner.


2002 ◽  
Vol 76 (24) ◽  
pp. 12783-12791 ◽  
Author(s):  
Christopher R. Logg ◽  
Aki Logg ◽  
Robert J. Matusik ◽  
Bernard H. Bochner ◽  
Noriyuki Kasahara

ABSTRACT The inability of replication-defective viral vectors to efficiently transduce tumor cells in vivo has prevented the successful application of such vectors in gene therapy of cancer. To address the need for more efficient gene delivery systems, we have developed replication-competent retroviral (RCR) vectors based on murine leukemia virus (MLV). We have previously shown that such vectors are capable of transducing solid tumors in vivo with very high efficiency. While the natural requirement of MLV infection for cell division imparts a certain degree of specificity for tumor cells, additional means for confining RCR vector replication to tumor cells are desirable. Here, we investigated the parameters critical for successful tissue-specific transcriptional control of RCR vector replication by replacing various lengths of the MLV enhancer/promoter with sequences derived either from the highly prostate-specific probasin (PB) promoter or from a more potent synthetic variant of the PB promoter. We assessed the transcriptional specificity of the resulting hybrid long terminal repeats (LTRs) and the cell type specificity and efficiency of replication of vectors containing these LTRs. Incorporation of PB promoter sequences effectively restricted transcription from the LTR to prostate-derived cells and imparted prostate-specific RCR vector replication but required the stronger synthetic promoter and retention of native MLV sequences in the vicinity of the TATA box for optimal replicative efficiency and specificity. Our results have thus identified promoter strength and positioning within the LTR as important determinants for achieving both high transduction efficiency and strict cell type specificity in transcriptionally targeted RCR vectors.


Development ◽  
1971 ◽  
Vol 26 (3) ◽  
pp. 523-542
Author(s):  
K. Straznicky ◽  
R. M. Gaze ◽  
M. J. Keating

The nature of the retinotectal projection from a compound (NN or TT) eye in Xenopus raises certain problems concerning the mode of formation of connexions between the eye and the tectum. Each half of the compound eye appears to spread its connexions across the entire extent of the (apparently normal) contralateral tectum. This could indicate a certain plasticity in the way in which optic fibres can connect with the tectum. Alternatively, it is conceivable that each (similar) half of the compound eye is only able to innervate its corresponding half-tectum; in which case the uninnervated half-tectum could remain undeveloped and the innervated half-tectum could overgrow to resemble a normal tectum. This mechanism would preserve the idea of a rigidly fixed cell-to-cell specificity between retina and tectum. In an attempt to distinguish between these two mechanisms (spreading or overgrown half-tectum) we have given each of a series of Xenopus embryos at stage 32 one compound eye (NN or TT). Then, shortly after metamorphosis, we uncrossed the optic chiasma and 6 months later recorded the retinotectal projections from each eye to the tecta. Thus by connecting up the normal eye to the suspect tectum, and the compound eye to the normal tectum, we used the normal side in each case to provide an indication of the degree of abnormality with which the other side was connected. The results showed that a compound eye (NN or TT), connected to a normal tectum, gave a typical reduplicated map across the entire tectum, whereas the normal eye, when connected to the tectum which was previously innervated by the compound eye, gave an approximately normal projection across the whole of that tectum. These results lead us to conclude that, in the Xenopus visual system, no strict cell-to-cell type specificity exists; rather, what is preserved throughout these experimental manoeuvres is the polarity and extent of the projection.


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