scholarly journals Activity-Dependent Activation of TrkB Neurotrophin Receptors in the Adult CNS

1999 ◽  
Vol 6 (3) ◽  
pp. 216-231 ◽  
Author(s):  
Raquel Aloyz ◽  
James P. Fawcett ◽  
David R. Kaplan ◽  
Richard A. Murphy ◽  
Freda D. Miller
Keyword(s):  
Cortical Neurons ◽  
Subcellular Fractionation ◽  
Neurotrophin Receptors ◽  
Noradrenergic Neurons ◽  
Trkb Receptors ◽  
Transient Activation ◽  
Pharmacological Blockade ◽  
Fast Activation ◽  
Rapid Activation ◽  
Activity Dependent

In this paper we have investigated the hypothesis that neural activity causes rapid activation of TrkB neurotrophin receptors in the adult mammalian CNS. These studies demonstrate that kainic acid-induced seizures led to a rapid and transient activation of TrkB receptors in the cortex. Subcellular fractionation demonstrated that these activated Trk receptors were preferentially enriched in the synaptosomal membrane fraction that also contained postsynaptic glutamate receptors. The fast activation of synaptic TrkB receptors could be duplicated in isolated cortical synaptosomes with KCl, presumably as a consequence of depolarization-induced BDNF release. Importantly, TrkB activation was also observed following pharmacological activation of brain-stem noradrenergic neurons, which synthesize and anterogradely transport BDNF; treatment with yohimbine led to activation of cortical TrkB receptors within 30 min. Pharmacological blockade of the postsynaptic α1-adrenergic receptors with prazosin only partially inhibited this effect, suggesting that the TrkB activation was partially due to a direct effect on postsynaptic cortical neurons. Together, these data support the hypothesis that activity causes release of BDNF from presynaptic terminals, resulting in a rapid activation of postsynaptic TrkB receptors. This activity-dependent TrkB activation could play a major role in morphological growth and remodelling in both the developing and mature nervous systems.

scholarly journals Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Philip Hasel ◽  
Owen Dando ◽  
Zoeb Jiwaji ◽  
Paul Baxter ◽  
Alison C. Todd ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neuronal Activity ◽  
Cortical Neurons ◽  
Synaptic Activity ◽  
Rna Seq ◽  
Metabolic Cooperation ◽  
Closely Related Species ◽  
Lactate Shuttle ◽  
Activity Dependent ◽  
Elevated Lactate

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.

scholarly journals Cdk5 Modulation of Mitogen-activated Protein Kinase Signaling Regulates Neuronal Survival

2007 ◽  
Vol 18 (2) ◽  
pp. 404-413 ◽  
Author(s):  
Ya-Li Zheng ◽  
Bing-Sheng Li ◽  
Jyotshna Kanungo ◽  
Sashi Kesavapany ◽  
Niranjana Amin ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cortical Neurons ◽  
Neuronal Cell ◽  
Mitogen Activated Protein Kinase ◽  
Significant Shift ◽  
Kinase Signaling ◽  
Small Interference Rna ◽  
Transient Activation ◽  
Mitogen Activated Protein ◽  
Protein Kinase Signaling

Cdk5, a cyclin-dependent kinase, is critical for neuronal development, neuronal migration, cortical lamination, and survival. Its survival role is based, in part, on “cross-talk” interactions with apoptotic and survival signaling pathways. Previously, we showed that Cdk5 phosphorylation of mitogen-activated protein kinase kinase (MEK)1 inhibits transient activation induced by nerve growth factor (NGF) in PC12 cells. To further explore the nature of this inhibition, we studied the kinetics of NGF activation of extracellular signal-regulated kinase (Erk)1/2 in cortical neurons with or without roscovitine, an inhibitor of Cdk5. NGF alone induced an Erk1/2-transient activation that peaked in 15 min and declined rapidly to baseline. Roscovitine, alone or with NGF, reached peak Erk1/2 activation in 30 min that was sustained for 48 h. Moreover, the sustained Erk1/2 activation induced apoptosis in cortical neurons. Significantly, pharmacological application of the MEK1 inhibitor PD98095 to roscovitine-treated cortical neurons prevented apoptosis. These results were also confirmed by knocking down Cdk5 activity in cortical neurons with Cdk5 small interference RNA. Apoptosis was correlated with a significant shift of phosphorylated tau and neurofilaments from axons to neuronal cell bodies. These results suggest that survival of cortical neurons is also dependent on tight Cdk5 modulation of the mitogen-activated protein kinase signaling pathway.

Requirement for BDNF in activity-dependent survival of cortical neurons

Science ◽  
1994 ◽  
Vol 263 (5153) ◽  
pp. 1618-1623 ◽  
Author(s):  
A Ghosh ◽  
J Carnahan ◽  
M. Greenberg
Keyword(s):  
Cortical Neurons ◽  
Activity Dependent

Development, learning and memory in large random networks of cortical neurons: lessons beyond anatomy

2002 ◽  
Vol 35 (1) ◽  
pp. 63-87 ◽  
Author(s):  
Shimon Marom ◽  
Goded Shahaf
Keyword(s):  
Functional Connectivity ◽  
Spontaneous Activity ◽  
Learning And Memory ◽  
Cortical Neurons ◽  
Ex Vivo ◽  
Adaptive Responses ◽  
Cortical Networks ◽  
Neural Learning ◽  
Wide Range ◽  
Activity Dependent

1. Introduction 631.1 Outline 631.2 Universals versus realizations in the study of learning and memory 642. Large random cortical networks developing ex vivo 652.1 Preparation 652.2 Measuring electrical activity 673. Spontaneous development 693.1 Activity 693.2 Connectivity 704. Consequences of spontaneous activity: pharmacological manipulations 724.1 Structural consequences 724.2 Functional consequences 735. Effects of stimulation 745.1 Response to focal stimulation 745.2 Stimulation-induced changes in connectivity 746. Embedding functionality in real neural networks 776.1 Facing the physiological definition of ‘reward’: two classes of theories 786.2 Closing the loop 797. Concluding remarks 848. Acknowledgments 859. References 85The phenomena of learning and memory are inherent to neural systems that differ from each other markedly. The differences, at the molecular, cellular and anatomical levels, reflect the wealth of possible instantiations of two neural learning and memory universals: (i) an extensive functional connectivity that enables a large repertoire of possible responses to stimuli; and (ii) sensitivity of the functional connectivity to activity, allowing for selection of adaptive responses. These universals can now be fully realized in ex-vivo developing neuronal networks due to advances in multi-electrode recording techniques and desktop computing. Applied to the study of ex-vivo networks of neurons, these approaches provide a unique view into learning and memory in networks, over a wide range of spatio-temporal scales. In this review, we summarize experimental data obtained from large random developing ex-vivo cortical networks. We describe how these networks are prepared, their structure, stages of functional development, and the forms of spontaneous activity they exhibit (Sections 2–4). In Section 5 we describe studies that seek to characterize the rules of activity-dependent changes in neural ensembles and their relation to monosynaptic rules. In Section 6, we demonstrate that it is possible to embed functionality into ex-vivo networks, that is, to teach them to perform desired firing patterns in both time and space. This requires ‘closing a loop’ between the network and the environment. Section 7 emphasizes the potential of ex-vivo developing cortical networks in the study of neural learning and memory universals. This may be achieved by combining closed loop experiments and ensemble-defined rules of activity-dependent change.

Differential subcellular targeting of PKC-ε in response to pharmacological or ischemic stimuli in intestinal epithelia

2005 ◽  
Vol 288 (1) ◽  
pp. G135-G142 ◽  
Author(s):  
Joshua M. V. Mammen ◽  
J. Cecilia Song ◽  
James Yoo ◽  
Peter S. Kim ◽  
Harold W. Davis ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Subcellular Fractionation ◽  
Intestinal Epithelial ◽  
Subcellular Targeting ◽  
Kinase Substrate ◽  
Intestinal Epithelia ◽  
Lateral Membrane ◽  
Transient Activation ◽  
Pkc Isoforms ◽  
Ischemic Stress

Ischemia is the central pathogenic factor underlying a spectrum of intestinal disorders. The study of the cellular signaling responses to ischemic stress in nonepithelial cells has progressed substantially in the previous several years, but little is known about the response in epithelial cells. Unique features of the epithelial response to ischemic stress suggest differential regulation with regards to signaling. The PKC family of proteins has been implicated in ischemic stress in nonepithelial systems. The role of PKC isoforms in chemical ischemia in intestinal epithelial cells is evaluated in this study. Additionally, the phosphorylation of the F-actin cross-linking protein myristoylated alanine-rich C kinase substrate (MARCKS) is also studied. Chemical ischemia resulted in the transient activation of only the isoform PKC-ε as detected by translocation employing the subcellular fractionation technique. The pharmacological agonists phorbol 12-myristate 13-acetate and carbachol also led to the translocation of PKC-ε. By immunofluoresence, MARCKS is noted to be located at the lateral membrane under control conditions. In response to carbachol, MARCKS translocates to the cytosol, indicating its phosphorylation, which is additionally confirmed biochemically. Consistent with this observation, carbachol induces the translocation of PKC-ε to proximity with MARCKS at the lateral membrane. In response to chemical ischemia, MARCKS fails to translocate and phosphorylation does not increase. Additionally, the translocation of PKC-ε is not to the lateral membrane but rather basally. The data suggest that the differential translocation of PKC-ε in response to pharmacological agonists versus ischemic stress may lead to different effects on downstream targets.

scholarly journals Neutrophils Stimulated with a Variety of Chemoattractants Exhibit Rapid Activation of p21-Activated Kinases (Paks): Separate Signals Are Required for Activation and Inactivation of Paks

1998 ◽  
Vol 18 (12) ◽  
pp. 7130-7138 ◽  
Author(s):  
RiYun Huang ◽  
Jian P. Lian ◽  
Dwight Robinson ◽  
John A. Badwey
Keyword(s):  
G Proteins ◽  
Platelet Activating Factor ◽  
Cell Types ◽  
Mitogen Activated Protein Kinase ◽  
Transient Activation ◽  
Anaphylatoxin C5a ◽  
Mitogen Activated Protein ◽  
Fmlp Receptor ◽  
Rapid Activation ◽  
G Protein Coupled

ABSTRACT Activation of the p21-activated protein kinases (Paks) was compared in neutrophils stimulated with a wide variety of agonists that bind to receptors coupled to heterotrimeric G proteins. Neutrophils stimulated with sulfatide, a ligand for the L-selectin receptor, or the chemoattractant fMet-Leu-Phe (fMLP), platelet-activating factor, leukotriene B4, interleukin-8, or the chemokine RANTES exhibited a rapid and transient activation of the 63- and 69-kDa Paks. These kinases exhibited maximal activation with each of these agonists within 15 s followed by significant inactivation at 3 min. In contrast, neutrophils treated with the chemoattractant and anaphylatoxin C5a exhibited a prolonged activation (>15 min) of these Paks even though the receptor for this ligand may activate the same overall population of complex G proteins as the fMLP receptor. Addition of fMLP to neutrophils already stimulated with C5a resulted in the inactivation of the 63- and 69-kDa Paks. Optimal activation of Paks could be observed at concentrations of these agonists that elicited only shape changes and chemotaxis in neutrophils. While all of the agonists listed above triggered quantitatively similar activation of the 63- and 69-kDa Paks, fMLP was far superior to the other stimuli in triggering activation of the c-Jun N-terminal kinase (JNK) and the p38 mitogen-activated protein kinase (MAPK). These data indicate that separate signals are required for activation and inactivation of Paks and that, in contrast to other cell types, activated Pak does not trigger activation of JNK or p38-MAPK in neutrophils. These results are consistent with the recent hypothesis that G-protein-coupled receptors may initiate signals independent of those transmitted by the α and βγ subunits of complex G proteins.

scholarly journals Temporally precise control of single-neuron spiking by juxtacellular nanostimulation

2017 ◽  
Vol 117 (3) ◽  
pp. 1363-1378 ◽  
Author(s):  
Maik C. Stüttgen ◽  
Lourens J. P. Nonkes ◽  
H. Rüdiger A. P. Geis ◽  
Paul H. Tiesinga ◽  
Arthur R. Houweling
Keyword(s):  
Short Duration ◽  
Cortical Neurons ◽  
Action Potentials ◽  
Neural Coding ◽  
Spike Trains ◽  
Precise Control ◽  
Neuronal Spike Trains ◽  
The Impact ◽  
Activity Dependent

Temporal patterns of action potentials influence a variety of activity-dependent intra- and intercellular processes and play an important role in theories of neural coding. Elucidating the mechanisms underlying these phenomena requires imposing spike trains with precisely defined patterns, but this has been challenging due to the limitations of existing stimulation techniques. Here we present a new nanostimulation method providing control over the action potential output of individual cortical neurons. Spikes are elicited through the juxtacellular application of short-duration fluctuating currents (“kurzpulses”), allowing for the sub-millisecond precise and reproducible induction of arbitrary patterns of action potentials at all physiologically relevant firing frequencies (<120 Hz), including minute-long spike trains recorded in freely moving animals. We systematically compared our method to whole cell current injection, as well as optogenetic stimulation, and show that nanostimulation performance compares favorably with these techniques. This new nanostimulation approach is easily applied, can be readily performed in awake behaving animals, and thus promises to be a powerful tool for systematic investigations into the temporal elements of neural codes, as well as the mechanisms underlying a wide variety of activity-dependent cellular processes. NEW & NOTEWORTHY Assessing the impact of temporal features of neuronal spike trains requires imposing arbitrary patterns of spiking on individual neurons during behavior, but this has been difficult to achieve due to limitations of existing stimulation methods. We present a technique that overcomes these limitations by using carefully designed short-duration fluctuating juxtacellular current injections, which allow for the precise and reliable evocation of arbitrary patterns of neuronal spikes in single neurons in vivo.

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