scholarly journals Critical role of de novo LTD in the formation and maintenance of hippocampal CA1 place-cell fields

2019 ◽  
Author(s):  
Donovan M Ashby ◽  
Jeremy K Seamans ◽  
Yu Tian Wang
Keyword(s):  
Direct Evidence ◽  
De Novo ◽  
Critical Role ◽  
Place Field ◽  
Hippocampal Ca1 ◽  
Place Fields ◽  
Freely Moving ◽  
Novel Environments

AbstractSynaptic plasticity mechanisms may help shape hippocampal place field representations of novel environments, yet direct evidence for how this occurs is lacking. Using multi-channel recordings in freely moving rats, we demonstrate that novelty exploration results in widespread de novo long-term depression (LTD) at hippocampal CA1 synapses in a pathway-specific manner, while blockade of LTD expression impairs the maintenance of newly formed place fields. This study therefore reveals an unrecognized role for LTD in the formation and maintenance of hippocampal place fields in novel environments.

scholarly journals LTD is involved in the formation and maintenance of rat hippocampal CA1 place-cell fields

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Donovan M. Ashby ◽  
Stan B. Floresco ◽  
Anthony G. Phillips ◽  
Alexander McGirr ◽  
Jeremy K. Seamans ◽  
...  
Keyword(s):  
Spatial Information ◽  
De Novo ◽  
Dorsal Hippocampus ◽  
Long Term Potentiation ◽  
Synaptic Depression ◽  
Place Field ◽  
Initial Exposure ◽  
Novel Environment ◽  
Place Fields

AbstractHippocampal synaptic plasticity includes both long-term potentiation (LTP) and long-term depression (LTD) of synaptic strength, and has been implicated in shaping place field representations that form upon initial exposure to a novel environment. However, direct evidence causally linking either LTP or LTD to place fields remains limited. Here, we show that hippocampal LTD regulates the acute formation and maintenance of place fields using electrophysiology and blocking specifically LTD in freely-moving rats. We also show that exploration of a novel environment produces a widespread and pathway specific de novo synaptic depression in the dorsal hippocampus. Furthermore, disruption of this pathway-specific synaptic depression alters both the dynamics of place field formation and the stability of the newly formed place fields, affecting spatial memory in rats. These results suggest that activity-dependent synaptic depression is required for the acquisition and maintenance of novel spatial information.

scholarly journals Interplay between somatic and dendritic inhibition promotes the emergence and stabilization of place fields

2018 ◽  
Author(s):  
Victor Pedrosa ◽  
Claudia Clopath
Keyword(s):  
Firing Rate ◽  
Place Cell ◽  
Place Cells ◽  
Place Field ◽  
Ca1 Neurons ◽  
Hippocampal Ca1 ◽  
Place Fields ◽  
Cell Stability ◽  
Cell Firing ◽  
Novel Environments

AbstractDuring exploration of novel environments, place fields are rapidly formed in hippocampal CA1 neurons. Place cell firing rate increases in early stages of exploration of novel environments but returns to baseline levels in familiar environments. However, although similar in amplitude and width, place fields in familiar environments are more stable than in novel environments. We propose a computational model of the hippocampal CA1 network, which describes the formation, the dynamics and the stabilization of place fields. We show that although somatic disinhibition is sufficient to form place cells, dendritic inhibition along with synaptic plasticity is necessary for stabilization. Our model suggests that place cell stability is due to large excitatory synaptic weights and large dendritic inhibition. We show that the interplay between somatic and dendritic inhibition balances the increased excitatory weights, so that place cells return to their baseline firing rate after exploration. Our model suggests that different types of interneurons are essential to unravel the mechanisms underlying place field plasticity. Finally, we predict that artificial induced dendritic events can shift place fields even after place field stabilization.

Persistent Pulmonary Hypertension of the Newborn: Role of Nitric Oxide

1995 ◽  
Vol 10 (6) ◽  
pp. 270-282
Author(s):  
Stella Kourembanas
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Structural Changes ◽  
Critical Role ◽  
Persistent Pulmonary Hypertension ◽  
Cell Contractility ◽  
Vasoactive Mediators ◽  
Nitric Oxide Therapy

Persistent pulmonary hypertension of the newborn (PPHN) is a common cause of respiratory failure in the full-term neonate. Molecular and cellular studies in vascular biology have revealed that endothelial-derived mediators play a critical role in the pathogenesis and treatment of PPHN. Endothelial-derived vasoconstrictors, like endothelin, may increase smooth muscle cell contractility and growth, leading to the physiologic and structural changes observed in the pulmonary arterioles of infants with this disease. On the other hand, decreased production of the endothelial-derived relaxing factor, nitric oxide, may exacerbate pulmonary vasoreactivity and lead to more severe pulmonary hypertension. Exogenous (inhaled) nitric oxide therapy reduces pulmonary vascular resistance and improves oxygenation. The safety and efficacy of this therapy in reducing the need for extracorporeal membrane oxygenation and decreasing long-term morbidity is being tested in several trials nationally and abroad. Understanding the basic mechanisms that regulate the gene expression and production of these vasoactive mediators will lead to improved preventive and therapeutic strategies for PPHN.

scholarly journals Distinct histone H3–H4 binding modes of sNASP reveal the basis for cooperation and competition of histone chaperones

2021 ◽  
Author(s):  
Chao-Pei Liu ◽  
Wenxing Jin ◽  
Jie Hu ◽  
Mingzhu Wang ◽  
Jingjing Chen ◽  
...  
Keyword(s):  
De Novo ◽  
Critical Role ◽  
Histone H3 ◽  
Coiled Coil ◽  
Dynamic Network ◽  
Histone Chaperones ◽  
Binding Modes ◽  
Nucleosome Assembly ◽  
Partially Unfolded

Chromosomal duplication requires de novo assembly of nucleosomes from newly synthesized histones, and the process involves a dynamic network of interactions between histones and histone chaperones. sNASP and ASF1 are two major histone H3–H4 chaperones found in distinct and common complexes, yet how sNASP binds H3–H4 in the presence and absence of ASF1 remains unclear. Here we show that, in the presence of ASF1, sNASP principally recognizes a partially unfolded Nα region of histone H3, and in the absence of ASF1, an additional sNASP binding site becomes available in the core domain of the H3–H4 complex. Our study also implicates a critical role of the C-terminal tail of H4 in the transfer of H3–H4 between sNASP and ASF1 and the coiled-coil domain of sNASP in nucleosome assembly. These findings provide mechanistic insights into coordinated histone binding and transfer by histone chaperones.

Neutral Sphingomyelinase is an Affective Valence-Dependent Regulator of Learning and Memory

2020 ◽  
Author(s):  
Liubov S Kalinichenko ◽  
Laila Abdel-Hafiz ◽  
An-Li Wang ◽  
Christiane Mühle ◽  
Nadine Rösel ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Behavioral Plasticity ◽  
De Novo ◽  
Positive Association ◽  
Superior Performance ◽  
Affective Valence ◽  
Neutral Sphingomyelinase ◽  
Healthy Humans

Abstract Sphingolipids and enzymes of the sphingolipid rheostat determine synaptic appearance and signaling in the brain, but sphingolipid contribution to normal behavioral plasticity is little understood. Here we asked how the sphingolipid rheostat contributes to learning and memory of various dimensions. We investigated the role of these lipids in the mechanisms of two different types of memory, such as appetitively and aversively motivated memory, which are considered to be mediated by different neural mechanisms. We found an association between superior performance in short- and long-term appetitively motivated learning and regionally enhanced neutral sphingomyelinase (NSM) activity. An opposite interaction was observed in an aversively motivated task. A valence-dissociating role of NSM in learning was confirmed in mice with genetically reduced NSM activity. This role may be mediated by the NSM control of N-methyl-d-aspartate receptor subunit expression. In a translational approach, we confirmed a positive association of serum NSM activity with long-term appetitively motivated memory in nonhuman primates and in healthy humans. Altogether, these data suggest a new sphingolipid mechanism of de-novo learning and memory, which is based on NSM activity.

scholarly journals THE CRITICAL ROLE OF THE HEALTHCARE SYSTEM ON LONG-TERM CARE ADMISSIONS OF PEOPLE WITH DEMENTIA

2017 ◽  
Vol 1 (suppl_1) ◽  
pp. 969-969
Author(s):  
N. Donnelly ◽  
N. Humphries ◽  
A. Hickey ◽  
F. Doyle
Keyword(s):  
Healthcare System ◽  
Long Term Care ◽  
Critical Role ◽  
Term Care ◽  
People With Dementia

TGF-β1-Induced Long-Term Changes in Neuronal Excitability in Aplysia Sensory Neurons Depend on MAPK

2006 ◽  
Vol 95 (5) ◽  
pp. 3286-3290 ◽  
Author(s):  
Jeannie Chin ◽  
Rong-Yu Liu ◽  
Leonard J. Cleary ◽  
Arnold Eskin ◽  
John H. Byrne
Keyword(s):  
Sensory Neuron ◽  
Transforming Growth Factor Beta ◽  
Neuronal Excitability ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Camp Response Element Binding ◽  
Long Term Changes ◽  
Tgf Β1

Transforming growth factor beta-1 (TGF-β1) plays important roles in the early development of the nervous system and has been implicated in neuronal plasticity in adult organisms. It induces long-term increases in sensory neuron excitability in Aplysia as well as a long-term enhancement of synaptic efficacy at sensorimotor synapses. In addition, TGF-β1 acutely regulates synapsin phosphorylation and reduces synaptic depression induced by low-frequency stimuli. Because of the critical role of MAPK in other forms of long-term plasticity in Aplysia, we examined the role of MAPK in TGF-β1-induced long-term changes in neuronal excitability. Prolonged (6 h) exposure to TGF-β1 induced long-term increases in excitability. We confirmed this finding and now report that exposure to TGF-β1 was sufficient to activate MAPK and increase nuclear levels of active MAPK. Moreover, TGF-β1 enhanced phosphorylation of the Aplysia transcriptional activator cAMP response element binding protein (CREB)1, a homologue to vertebrate CREB. Both the TGF-β1-induced long-term changes in neuronal excitability and the phosphorylation of CREB1 were blocked in the presence of an inhibitor of the MAPK cascade, confirming a role for MAPK in long-term modulation of sensory neuron function.

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