Synaptically-targeted long non-coding RNA SLAMR promotes structural plasticity by increasing translation and CaMKII activity

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 27, 2024

Long noncoding RNAs (lncRNAs) play crucial roles in maintaining cell homeostasis and function. However, it remains largely unknown whether how neuronal activity impacts the transcriptional regulation of lncRNAs, or if this leads to synapse-related changes contributes formation long-term memories. Here, we report identification a lncRNA, SLAMR, which becomes enriched CA1-hippocampal neurons upon contextual fear conditioning but not CA3 neurons. SLAMR is transported along dendrites via molecular motor KIF5C recruited synapse stimulation. Loss function reduces dendritic complexity impairs activity-dependent spine structural plasticity translation. Gain contrast, enhances complexity, density, Analyses interactome reveal its association with CaMKIIα protein through 220-nucleotide element also involved transport. A CaMKII reporter reveals basal reduction loss-of-function. Furthermore, selective loss CA1 disrupts consolidation memory male mice, without affecting their acquisition, recall, extinction, spatial memory. Together, these results provide new functional insight into at fear.

Language: Английский

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Half a century legacy of long-term potentiation

Current Biology, Journal Year: 2024, Volume and Issue: 34(13), P. R640 - R662

Published: July 1, 2024

Language: Английский

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A biochemical description of postsynaptic plasticity—with timescales ranging from milliseconds to seconds

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(7)

Published: Feb. 7, 2024

Synaptic plasticity [long-term potentiation/depression (LTP/D)], is a cellular mechanism underlying learning. Two distinct types of early LTP/D (E-LTP/D), acting on very different time scales, have been observed experimentally—spike timing dependent (STDP), scales tens ms; and behavioral scale synaptic (BTSP), seconds. BTSP candidate for rapid learning spatial location by place cells. Here, computational model the induction E-LTP/D at spine head synapse hippocampal pyramidal neuron developed. The single-compartment represents two interacting biochemical pathways activation (phosphorylation) kinase (CaMKII) with phosphatase, ion inflow through channels (NMDAR, CaV1,Na). reactions are represented deterministic system differential equations, detailed description CaMKII that includes opening compact state CaMKII. This single captures realistic responses (temporal profiles differing timescales) STDP their asymmetries. simulations distinguish several mechanisms vs. BTSP, including i) flow Ca 2 + NMDAR CaV1 channels, ii) origin in also realizes priming E-LTP induced CaV1.3 channels. Once head, this small additional opens CaMKII, placing ready subsequent LTP.

Language: Английский

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Synaptic Plasticity in the Hippocampus

Oxford University Press eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 405 - 500

Published: Jan. 1, 2025

Abstract This chapter provides an overview of activity-dependent synaptic plasticity in the hippocampus. It outlines basic properties long-term potentiation (LTP) and depression (LTD) pathways that form core hippocampal trisynaptic circuit, notably Schaffer collateral/commissural (SCC) pathway connecting CA3 to CA1 pyramidal cells. Other significant include projections from medial later entorhinal cortex (EC) distal dendrites principal cells all subfields mossy fiber projection dendate granule The then delves into physiological cell biological mechanisms its contribution hippocampus-dependent memory, including relationship engrams. Another major focus is role dysregulated synaptopathies, with a particular emphasis on neurodevelopmental, psychiatric neurodegenerative brain disorders.

Language: Английский

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Nonlinear slow-timescale mechanisms in synaptic plasticity

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 82, P. 102778 - 102778

Published: Aug. 30, 2023

Language: Английский

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Variable recruitment of distal tuft dendrites shapes new hippocampal place fields

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 28, 2024

SUMMARY Hippocampal pyramidal neurons support episodic memory by integrating complementary information streams into new ‘place fields’. Distal tuft dendrites are widely thought to initiate place field formation locally generating prolonged, globally-spreading Ca 2+ spikes known as plateau potentials. However, the hitherto experimental inaccessibility of distal in hippocampus has rendered their vivo function entirely unknown. Here we gained direct optical access this elusive dendritic compartment. We report that do not serve point origin for field-forming Instead, timing and extent peri-formation recruitment is variable closely predicts multiple properties resultant fields. Therefore, play a more powerful role hippocampal feature selectivity than simply initiating formation. Moreover, accompanied global influx previously thought. In addition shaping somatic fields, possess own local Tuft fields back-shifted relative soma appear maintain via post-formation Through observation, provide revised basis during navigational learning.

Language: Английский

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Unraveling the mysteries of dendritic spine dynamics: Five key principles shaping memory and cognition

Proceedings of the Japan Academy Series B, Journal Year: 2023, Volume and Issue: 99(8), P. 254 - 305

Published: Oct. 10, 2023

Recent research extends our understanding of brain processes beyond just action potentials and chemical transmissions within neural circuits, emphasizing the mechanical forces generated by excitatory synapses on dendritic spines to modulate presynaptic function. From in vivo vitro studies, we outline five central principles synaptic mechanics function: P1: Stability - Underpinning integral relationship between structure function spine synapses. P2: Extrinsic dynamics Highlighting synapse-selective structural plasticity which plays a crucial role Hebbian associative learning, distinct from pathway-selective long-term potentiation (LTP) depression (LTD). P3: Neuromodulation Analyzing G-protein-coupled receptors, particularly dopamine time-sensitive modulation learning frameworks such as Pavlovian classical conditioning Thorndike's reinforcement (RL). P4: Instability Addressing intrinsic memory management during continual spotlighting their "spine dysgenesis" associated with mental disorders. P5: Mechanics Exploring how influence both sides establish traces short- memory, thereby aiding integration functions. We also delve into historical background foresee impending challenges.

Language: Английский

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Hippocampal place code plasticity in CA1 requires postsynaptic membrane fusion

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 21, 2023

Rapid delivery of glutamate receptors to the postsynaptic membrane via vesicle fusion is a central component synaptic plasticity. However, it unknown how this process supports specific neural computations during behavior. To bridge gap, we combined conditional genetic deletion machinery, Syntaxin3 (Stx3), in hippocampal CA1 neurons mice with population vivo calcium imaging. This approach revealed that Stx3 necessary for forming dynamics support novelty processing, spatial reward memory and offline consolidation. In contrast, was dispensable maintaining aspects code exist presynaptic such as representations context space. Thus, manipulating identified specifically require restructuring trafficking distinguished them from representation could be inherited upstream brain regions or learned through other mechanisms.

Language: Английский

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Early hippocampal hyperexcitability and synaptic reorganization in mouse models of amyloidosis

iScience, Journal Year: 2024, Volume and Issue: 27(9), P. 110629 - 110629

Published: Aug. 2, 2024

Abnormal hippocampal activity is an early stage pathology of b-amyloidosis models Synaptic reorganization in CA1 pyramidal neurons follows altered Juvenile mice show simultaneous gain and loss synapses based on dendritic location Aged a broader across cellular compartments

Language: Английский

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A Generalized Framework for the Calcium Control Hypothesis Describes Weight-Dependent Synaptic Changes in Behavioral Time Scale Plasticity

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: July 15, 2023

Abstract The brain modifies synaptic strengths to store new information via long-term potentiation (LTP) and depression (LTD). Evidence has mounted that plasticity is controlled concentrations of calcium ([Ca 2+ ]) in postsynaptic spines. Several mathematical models describe this phenomenon, including those Shouval, Bear, Cooper (SBC) (Shouval et al., 2002, 2010) Graupner Brunel (GB)(Graupner & Brunel, 2012). Here we suggest a generalized version the SBC GB models, based on fixed point – learning rate (FPLR) framework, where [Ca ] specifies toward which weight approaches asymptotically at ]-dependent rate. FPLR framework offers straightforward phenomenological interpretation calcium-based plasticity: concentration tells it going how fast goes there . can flexibly incorporate various experimental findings, existence multiple regions no occurs, or cerebellar Purkinje cells, directionality changes thought be reversed relative cortical hippocampal neurons. We also modeling approach captures dependency late-phase stabilization protein synthesis. demonstrate due asymptotic, saturating nature rule, result frequency- spike-timing-dependent protocols are weight-dependent. Finally, show explain plateau potential-induced place field formation CA1 neurons, known as behavioral time scale (BTSP).

Language: Английский

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