scholarly journals Guiding synaptic plasticity: Novel roles for netrin‐1 in synaptic plasticity and memory formation in the adult brain

2020 ◽  
Author(s):  
Stephen D. Glasgow ◽  
Edward S. Ruthazer ◽  
Timothy E. Kennedy
Keyword(s):  
Synaptic Plasticity ◽  
Memory Formation ◽  
Adult Brain

BDNF and Control of Synaptic Plasticity in the Adult Brain

2009 ◽  
Vol 24 (S1) ◽  
pp. 1-1
Author(s):  
C. Bramham
Keyword(s):  
Synaptic Plasticity ◽  
Dentate Gyrus ◽  
Antidepressant Drugs ◽  
Long Term Potentiation ◽  
Memory Formation ◽  
Adult Brain ◽  
Early Gene ◽  
Perforant Path ◽  
Mammalian Brain

Experience-dependent changes in synaptic connectivity are thought to play a vital role not only in memory formation, but also in long-term adaptive responses involved in mood regulation, reward behavior, and pain control. The neurotrophin, brain-derived neurotrophic factor (BDNF), which has recently been implicated in memory formation and aspects of major depression, is also an important regulator of long-term synaptic plasticity in the adult mammalian brain. We have investigated BDNF function in the dentate gyrus, a brain region implicated in depression and the action of antidepressant drugs. Local infusion of BDNF into the dentate gyrus generated a long-term potentiation (LTP) of synaptic efficacy at medial perforant path-granule cell synapses. This LTP is associated with expression of the immediate early gene, Arc, in postsynaptic granule cells and transport of Arc mRNA to synaptic regions on dendrites. Using local infusion of antisense oligodeoxynucleotides to block Arc synthesis, we show that Arc is required for the induction and time-dependent consolidation of BDNF-induced LTP. The sustained synthesis of Arc during a critical time-window is required for local expansion of the actin cytoskeletal network in dendritic spines. These results identify Arc as a critical mediator of BDNF in long-term synaptic plasticity in the adult brain. Microarray expression profiling has further revealed a panel of genes that, like Arc, are strongly upregulated following acute BDNF infusion or chronic treatment with the antidepressant fluoxetine.

scholarly journals Loss of Non-Apoptotic Role of Caspase-3 in the PINK1 Mouse Model of Parkinson’s Disease

2019 ◽  
Vol 20 (14) ◽  
pp. 3407 ◽  
Author(s):  
Paola Imbriani ◽  
Annalisa Tassone ◽  
Maria Meringolo ◽  
Giulia Ponterio ◽  
Graziella Madeo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Synaptic Plasticity ◽  
Mouse Model ◽  
Caspase 3 ◽  
Cysteine Proteases ◽  
Synaptic Function ◽  
Adult Brain ◽  
Striatal Slices

Caspases are a family of conserved cysteine proteases that play key roles in multiple cellular processes, including programmed cell death and inflammation. Recent evidence shows that caspases are also involved in crucial non-apoptotic functions, such as dendrite development, axon pruning, and synaptic plasticity mechanisms underlying learning and memory processes. The activated form of caspase-3, which is known to trigger widespread damage and degeneration, can also modulate synaptic function in the adult brain. Thus, in the present study, we tested the hypothesis that caspase-3 modulates synaptic plasticity at corticostriatal synapses in the phosphatase and tensin homolog (PTEN) induced kinase 1 (PINK1) mouse model of Parkinson’s disease (PD). Loss of PINK1 has been previously associated with an impairment of corticostriatal long-term depression (LTD), rescued by amphetamine-induced dopamine release. Here, we show that caspase-3 activity, measured after LTD induction, is significantly decreased in the PINK1 knockout model compared with wild-type mice. Accordingly, pretreatment of striatal slices with the caspase-3 activator α-(Trichloromethyl)-4-pyridineethanol (PETCM) rescues a physiological LTD in PINK1 knockout mice. Furthermore, the inhibition of caspase-3 prevents the amphetamine-induced rescue of LTD in the same model. Our data support a hormesis-based double role of caspase-3; when massively activated, it induces apoptosis, while at lower level of activation, it modulates physiological phenomena, like the expression of corticostriatal LTD. Exploring the non-apoptotic activation of caspase-3 may contribute to clarify the mechanisms involved in synaptic failure in PD, as well as in view of new potential pharmacological targets.

scholarly journals Protein kinase D promotes plasticity-induced F-actin stabilization in dendritic spines and regulates memory formation

2015 ◽  
Vol 210 (5) ◽  
pp. 771-783 ◽  
Author(s):  
Norbert Bencsik ◽  
Zsófia Szíber ◽  
Hanna Liliom ◽  
Krisztián Tárnok ◽  
Sándor Borbély ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Protein Kinase ◽  
Dendritic Spines ◽  
Morphological Changes ◽  
Long Term Potentiation ◽  
Memory Formation ◽  
Protein Kinase D

Actin turnover in dendritic spines influences spine development, morphology, and plasticity, with functional consequences on learning and memory formation. In nonneuronal cells, protein kinase D (PKD) has an important role in stabilizing F-actin via multiple molecular pathways. Using in vitro models of neuronal plasticity, such as glycine-induced chemical long-term potentiation (LTP), known to evoke synaptic plasticity, or long-term depolarization block by KCl, leading to homeostatic morphological changes, we show that actin stabilization needed for the enlargement of dendritic spines is dependent on PKD activity. Consequently, impaired PKD functions attenuate activity-dependent changes in hippocampal dendritic spines, including LTP formation, cause morphological alterations in vivo, and have deleterious consequences on spatial memory formation. We thus provide compelling evidence that PKD controls synaptic plasticity and learning by regulating actin stability in dendritic spines.

scholarly journals Synaptic plasticity-dependent competition rule influences memory formation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yire Jeong ◽  
Hye-Yeon Cho ◽  
Mujun Kim ◽  
Jung-Pyo Oh ◽  
Min Soo Kang ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Fear Conditioning ◽  
Long Term Potentiation ◽  
Memory Formation ◽  
Specific Pattern ◽  
Memory Encoding ◽  
Competition Rule ◽  
Term Potentiation ◽  
Input Activity

AbstractMemory is supported by a specific collection of neurons distributed in broad brain areas, an engram. Despite recent advances in identifying an engram, how the engram is created during memory formation remains elusive. To explore the relation between a specific pattern of input activity and memory allocation, here we target a sparse subset of neurons in the auditory cortex and thalamus. The synaptic inputs from these neurons to the lateral amygdala (LA) are not potentiated by fear conditioning. Using an optogenetic priming stimulus, we manipulate these synapses to be potentiated by the learning. In this condition, fear memory is preferentially encoded in the manipulated cell ensembles. This change, however, is abolished with optical long-term depression (LTD) delivered shortly after training. Conversely, delivering optical long-term potentiation (LTP) alone shortly after fear conditioning is sufficient to induce the preferential memory encoding. These results suggest a synaptic plasticity-dependent competition rule underlying memory formation.

scholarly journals Astrocyte-secreted IL-33 mediates homeostatic synaptic plasticity in the adult hippocampus

2020 ◽  
Vol 118 (1) ◽  
pp. e2020810118
Author(s):  
Ye Wang ◽  
Wing-Yu Fu ◽  
Kit Cheung ◽  
Kwok-Wang Hung ◽  
Congping Chen ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Activity ◽  
Hippocampal Slices ◽  
Memory Formation ◽  
Conditional Knockout ◽  
Acute Administration ◽  
Excitatory Synapses ◽  
Homeostatic Synaptic Plasticity ◽  
Hippocampal Ca1

Hippocampal synaptic plasticity is important for learning and memory formation. Homeostatic synaptic plasticity is a specific form of synaptic plasticity that is induced upon prolonged changes in neuronal activity to maintain network homeostasis. While astrocytes are important regulators of synaptic transmission and plasticity, it is largely unclear how they interact with neurons to regulate synaptic plasticity at the circuit level. Here, we show that neuronal activity blockade selectively increases the expression and secretion of IL-33 (interleukin-33) by astrocytes in the hippocampal cornu ammonis 1 (CA1) subregion. This IL-33 stimulates an increase in excitatory synapses and neurotransmission through the activation of neuronal IL-33 receptor complex and synaptic recruitment of the scaffold protein PSD-95. We found that acute administration of tetrodotoxin in hippocampal slices or inhibition of hippocampal CA1 excitatory neurons by optogenetic manipulation increases IL-33 expression in CA1 astrocytes. Furthermore, IL-33 administration in vivo promotes the formation of functional excitatory synapses in hippocampal CA1 neurons, whereas conditional knockout of IL-33 in CA1 astrocytes decreases the number of excitatory synapses therein. Importantly, blockade of IL-33 and its receptor signaling in vivo by intracerebroventricular administration of its decoy receptor inhibits homeostatic synaptic plasticity in CA1 pyramidal neurons and impairs spatial memory formation in mice. These results collectively reveal an important role of astrocytic IL-33 in mediating the negative-feedback signaling mechanism in homeostatic synaptic plasticity, providing insights into how astrocytes maintain hippocampal network homeostasis.

scholarly journals Promoter-Specific Effects of DREADD Modulation on Hippocampal Synaptic Plasticity and Memory Formation

2016 ◽  
Vol 36 (12) ◽  
pp. 3588-3599 ◽  
Author(s):  
A. J. Lopez ◽  
E. Kramar ◽  
D. P. Matheos ◽  
A. O. White ◽  
J. Kwapis ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Memory Formation ◽  
Specific Effects ◽  
Hippocampal Synaptic Plasticity

Estrogenic Regulation of Synaptic Actin Proteins and Plasticity

2020 ◽  
pp. 69-82
Author(s):  
Enikö A. Kramár
Keyword(s):  
Synaptic Plasticity ◽  
Long Term Potentiation ◽  
Synaptic Strength ◽  
Adult Brain ◽  
Actin Dynamics ◽  
Signaling Cascade ◽  
Term Potentiation ◽  
Estrogenic Regulation ◽  
Estradiol Levels

Estrogens are rapid and potent facilitators of synaptic plasticity in the adult brain; however, the steps that link estrogens to factors that regulate synaptic strength remain unclear. The present chapter will first review the acute effects of 17β‎-estradiol on synaptic transmission and long-term potentiation (LTP). It will then describe a synaptic model used to study the substrates of LTP and provide evidence for the ability of estradiol to rapidly engage a selective actin signaling cascade associated with the consolidation of LTP. Finally, it will be shown that chronic reductions in estradiol levels disrupt LTP and actin dynamics but can be reversed by acute infusions of the hormone. It is concluded here that estradiol can promote learning-related plasticity by modifying the synaptic cytoskeleton.

scholarly journals Lack of Neuronal Glycogen Impairs Memory Formation and Learning-Dependent Synaptic Plasticity in Mice

2019 ◽  
Vol 13 ◽  
Author(s):  
Jordi Duran ◽  
Agnès Gruart ◽  
Olga Varea ◽  
Iliana López-Soldado ◽  
José M. Delgado-García ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Memory Formation
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