Data-driven synapse classification reveals a logic of glutamate receptor composition DOI Creative Commons
Kristina D. Micheva, Anish K. Simhal,

Jenna Schardt

et al.

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

Published: Dec. 13, 2024

Summary The rich diversity of synapses facilitates the capacity neural circuits to transmit, process and store information. Here, we used multiplex super-resolution proteometric imaging through array tomography define features single in adult mouse neocortex. We find that glutamatergic cluster into subclasses parallel distinct biochemical functional categories receptor subunits: GluA1/4, GluA2/3 GluN1/GluN2B. Two these align with physiological expectations based on synaptic plasticity: large AMPAR-rich may represent potentiated synapses, whereas small NMDAR-rich suggest “silent” synapses. NMDA content correlates spine neck diameter, thus potential for coupling parent dendrite. Conjugate tomography’s rigorous registration immunofluorescence electron microscopy provides validation future studies other systems. No barriers prevent generalization this approach species, laying a foundation human disorders therapeutics. Highlights enables validates single-synapse proteometry Glutamate identifies places synapse ultrastructural context Subclasses established molecular plasticity Graphical Abstract

Language: Английский

CaMKII autophosphorylation is the only enzymatic event required for synaptic memory DOI Creative Commons
Xiumin Chen, Qixu Cai, Jing Zhou

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(26)

Published: June 18, 2024

Ca 2+ /calmodulin (CaM)-dependent kinase II (CaMKII) plays a critical role in long-term potentiation (LTP), well-established model for learning and memory through the enhancement of synaptic transmission. Biochemical studies indicate that CaMKII catalyzes phosphotransferase (kinase) reaction both itself (autophosphorylation) multiple downstream target proteins. However, whether either type phosphorylation any enhancing action remains hotly contested. We have designed series experiments to define minimal requirements by CaMKII. find autophosphorylation T286 further binding GluN2B subunit are required initiating LTP its maintenance (synaptic memory). Once bound NMDA receptor, occurs absence protein phosphorylation. Thus, only two memory.

Language: Английский

Citations

16
Dendritic, delayed, stochastic CaMKII activation in behavioural time scale plasticity DOI Creative Commons
Anant Jain, Yoshihisa Nakahata,

Tristano Pancani

et al.

Nature, Journal Year: 2024, Volume and Issue: 635(8037), P. 151 - 159

Published: Oct. 9, 2024

Behavioural time scale plasticity (BTSP) is non-Hebbian induced by integrating presynaptic and postsynaptic components separated a behaviourally relevant (seconds)

Language: Английский

Citations

10
Brain-wide microstrokes affect the stability of memory circuits in the hippocampus DOI Creative Commons
Hendrik Heiser,

Filippo Kiessler,

Adrian Hoffmann

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 11, 2025

Abstract Cognitive deficits affect over 70% of stroke survivors, yet the mechanisms by which multiple small ischemic events contribute to cognitive decline remain poorly understood. In this study, we employed chronic two-photon calcium imaging longitudinally track fate individual neurons in hippocampus mice navigating a virtual reality environment, both before and after inducing brain-wide microstrokes. Our findings reveal that, under normal conditions, hippocampal exhibit varying degrees stability their spatial memory coding. However, microstrokes disrupted functional network architecture, leading impairments. Notably, preservation stable coding place cells, along with stability, precision, persistence network, was strongly predictive outcomes. Mice more synchronously active cells near important locations demonstrated recovery from impairment. This study uncovers critical cellular responses alterations following brain injury, providing foundation for novel therapeutic strategies preventing decline.

Language: Английский

Citations

1
Synaptic Basis of Behavioral Timescale Plasticity DOI Open Access
Kevin C. Gonzalez, Adrian Negrean, Zhenrui Liao

et al.

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

Published: Oct. 5, 2023

Abstract Learning and memory are fundamental to adaptive behavior cognition. Various forms of synaptic plasticity have been proposed as cellular substrates for the emergence feature selectivity in neurons underlying episodic memory. However, despite decades work, our understanding how underlies encoding remains limited, largely due a shortage tools technical challenges associated with visualization at single-neuron resolution awake-behaving animals. Behavioral Timescale Synaptic Plasticity (BTSP) postulates that inputs active during seconds-long time window preceding immediately following large depolarizing plateau spike potentiated, while outside this depressed. We experimentally tested model vivo mice using an all-optical approach by inducing place fields (PFs) single CA1 pyramidal (CA1PNs) monitoring spatiotemporal tuning individual dendritic spines changes their corresponding weights. identified asymmetric kernel resulting from bidirectional modifications weights around burst induction. Surprisingly, work also uncovered compartment-specific differences magnitude temporal expression between basal oblique dendrites CA1PNs. Our results provide first experimental evidence linking rapid spatial hippocampal neurons, critical prerequisite

Language: Английский

Citations

17
A biochemical description of postsynaptic plasticity—with timescales ranging from milliseconds to seconds DOI Creative Commons
Guanchun Li,

David W. McLaughlin,

Charles S. Peskin

et al.

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

Citations

6
CaMKII activity and metabolic imbalance-related neurological diseases: Focus on vascular dysfunction, synaptic plasticity, amyloid beta accumulation, and lipid metabolism DOI Open Access
Jeongsik Yong, Juhyun Song

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116688 - 116688

Published: April 30, 2024

Metabolic syndrome (MetS) is characterized by insulin resistance, hyperglycemia, excessive fat accumulation and dyslipidemia, known to be accompanied neuropathological symptoms such as memory loss, anxiety, depression. As the number of MetS patients rapidly increasing globally, studies on mechanisms metabolic imbalance-related neuropathology are emerging an important issue. Ca2+/calmodulin-dependent kinase II (CaMKII) main Ca2+ sensor contributes diverse intracellular signaling in peripheral organs central nervous system (CNS). CaMKII exerts functions cells, related RNA splicing, reactive oxygen species (ROS) generation, cytoskeleton, protein-protein interactions. In CNS, regulates vascular function, neuronal circuits, neurotransmission, synaptic plasticity, amyloid beta toxicity, lipid metabolism, mitochondrial function. Here, we review recent evidence for role neuropathologic issues associated with disorders.

Language: Английский

Citations

5
Synaptic basis of feature selectivity in hippocampal neurons DOI
Kevin C. Gonzalez, Adrian Negrean, Zhenrui Liao

et al.

Nature, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 18, 2024

Language: Английский

Citations

5
Learning, Fast and Slow: Single- and Many-Shot Learning in the Hippocampus DOI
Zhenrui Liao, Attila Losonczy

Annual Review of Neuroscience, Journal Year: 2024, Volume and Issue: 47(1), P. 187 - 209

Published: April 25, 2024

The hippocampus is critical for memory and spatial navigation. ability to map novel environments, as well more abstract conceptual relationships, fundamental the cognitive flexibility that humans other animals require survive in a dynamic world. In this review, we survey recent advances our understanding of how implemented anatomically functionally by hippocampal circuitry, during both active exploration (online) rest (offline). We discuss advantages limitations spike timing–dependent plasticity recently discovered behavioral timescale synaptic supporting distinct learning modes hippocampus. Finally, suggest complementary roles these types explaining many-shot single-shot rules could work together support maps.

Language: Английский

Citations

4
A revised view of the role of CaMKII in learning and memory DOI
K. Ulrich Bayer, Karl-Peter Giese

Nature Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 18, 2024

Language: Английский

Citations

4
Eligibility traces as a synaptic substrate for learning DOI
Harel Z. Shouval, Alfredo Kirkwood

Current Opinion in Neurobiology, Journal Year: 2025, Volume and Issue: 91, P. 102978 - 102978

Published: Feb. 17, 2025

Language: Английский

Citations

0