ΔFOSB: A Potentially Druggable Master Orchestrator of Activity-Dependent Gene Expression

Author(s):  
Alfred J. Robison ◽  
Eric J. Nestler
2011 ◽  
Vol 71 ◽  
pp. e114
Author(s):  
Atsumi Mori ◽  
Mamoru Fukuchi ◽  
Yuya Kirikoshi ◽  
Ichiro Takasaki ◽  
Aiko Azegami ◽  
...  

2018 ◽  
Vol 24 (5) ◽  
pp. 471-485 ◽  
Author(s):  
Jillian Belgrad ◽  
R. Douglas Fields

The temporal coding of action potential activity is fundamental to nervous system function. Here we consider how gene expression in neurons is regulated by specific patterns of action potential firing, with an emphasis on new information on epigenetic regulation of gene expression. Patterned action potential activity activates intracellular signaling networks selectively in accordance with the kinetics of activation and inactivation of second messengers, phosphorylation and dephosphorylation of protein kinases, and cytoplasmic and nuclear calcium dynamics, which differentially activate specific transcription factors. Increasing evidence also implicates activity-dependent regulation of epigenetic mechanisms to alter chromatin architecture. Changes in three-dimensional chromatin structure, including chromatin compaction, looping, double-stranded DNA breaks, histone and DNA modification, are altered by action potential activity to selectively inhibit or promote transcription of specific genes. These mechanisms of activity-dependent regulation of gene expression are important in neural development, plasticity, and in neurological and psychological disorders.


2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Philip Hasel ◽  
Owen Dando ◽  
Zoeb Jiwaji ◽  
Paul Baxter ◽  
Alison C. Todd ◽  
...  

Abstract The influence that neurons exert on astrocytic function is poorly understood. To investigate this, we first developed a system combining cortical neurons and astrocytes from closely related species, followed by RNA-seq and in silico species separation. This approach uncovers a wide programme of neuron-induced astrocytic gene expression, involving Notch signalling, which drives and maintains astrocytic maturity and neurotransmitter uptake function, is conserved in human development, and is disrupted by neurodegeneration. Separately, hundreds of astrocytic genes are acutely regulated by synaptic activity via mechanisms involving cAMP/PKA-dependent CREB activation. This includes the coordinated activity-dependent upregulation of major astrocytic components of the astrocyte–neuron lactate shuttle, leading to a CREB-dependent increase in astrocytic glucose metabolism and elevated lactate export. Moreover, the groups of astrocytic genes induced by neurons or neuronal activity both show age-dependent decline in humans. Thus, neurons and neuronal activity regulate the astrocytic transcriptome with the potential to shape astrocyte–neuron metabolic cooperation.


2015 ◽  
Vol 4 (11) ◽  
pp. 823-833 ◽  
Author(s):  
Kenneth A. Dyar ◽  
Stefano Ciciliot ◽  
Guidantonio Malagoli Tagliazucchi ◽  
Giorgia Pallafacchina ◽  
Jana Tothova ◽  
...  

2002 ◽  
Vol 277 (51) ◽  
pp. 49585-49590 ◽  
Author(s):  
Bastiano Sanna ◽  
Dana Kramer ◽  
Armando A. Genazzani

Activity-dependent gene expression is thought to be important in shaping neuronal development and in modifying the protein content of neurons. Ca2+entry into neurons appears to be one of the key effectors of activity-dependent gene expression. Among the possible downstream targets of calcium, the protein phosphatase calcineurin represents a prime candidate. We hereby report that in cultured cerebellar granule cells the activation of the Ca2+/calcineurin pathway via either voltage- or ligand- operated Ca2+channels regulates MALS-1 and MALS-2 expression at the transcriptional level. These proteins are integral parts of the post-synaptic density and are also involved in receptor trafficking. MALS regulation is not at the level of mRNA stability and does not requirede novoprotein synthesis, thereby suggesting a direct pathway. These data suggest that Ca2+entry by means of calcineurin is capable of controlling the structure of the post-synaptic density by controlling the expression of key components at the transcriptional level.


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