Decrease of Rab11 prevents the correct dendritic arborization, synaptic plasticity and spatial memory formation

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.

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Nuclear factor of activated T cells (NFATc4) is required for BDNF-dependent survival of adult-born neurons and spatial memory formation in the hippocampus

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1202068109 ◽

2012 ◽

Vol 109 (23) ◽

pp. E1499-E1508 ◽

Cited By ~ 34

Author(s):

G. Quadrato ◽

M. Benevento ◽

S. Alber ◽

C. Jacob ◽

E. M. Floriddia ◽

...

Keyword(s):

T Cells ◽

Spatial Memory ◽

Memory Formation ◽

Nuclear Factor ◽

Activated T Cells ◽

Adult Born Neurons

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Synaptic plasticity-dependent competition rule influences memory formation

Nature Communications ◽

10.1038/s41467-021-24269-4 ◽

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.

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

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2020810118 ◽

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.

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