A thalamic-hippocampal CA1 signal for contextual fear memory suppression, extinction, and discrimination

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Oct. 24, 2023

Abstract The adaptive regulation of fear memories is a crucial neural function that prevents inappropriate expression. Fear can be acquired through contextual conditioning (CFC) which relies on the hippocampus. thalamic nucleus reuniens (NR) necessary to extinguish and innervates hippocampal CA1. However, role NR-CA1 pathway in unknown. We developed head-restrained virtual reality CFC paradigm, demonstrate mice acquire context-dependent responses. found inhibiting following lengthens duration fearful freezing epochs, increases generalization, delays extinction. Using vivo imaging, we recorded NR-axons innervating CA1 become tuned CFC. conclude actively suppresses by disrupting memory retrieval during behavior, process also reduces generalization accelerates

Language: Английский

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Retrograde endocannabinoid signaling at inhibitory synapses in vivo

Science, Journal Year: 2024, Volume and Issue: 383(6686), P. 967 - 970

Published: Feb. 29, 2024

Endocannabinoid (eCB)–mediated suppression of inhibitory synapses has been hypothesized, but this not yet demonstrated to occur in vivo because the difficulty tracking eCB dynamics and synaptic plasticity during behavior. In mice navigating a linear track, we observed location-specific signaling hippocampal CA1 place cells, was detected both postsynaptic membrane presynaptic axons. All-optical investigation responses revealed that depolarization followed by potentials. Furthermore, interneuron-specific cannabinoid receptor deletion altered cell tuning. Therefore, rapid, postsynaptic, activity-dependent modulates on timescale seconds

Language: Английский

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Dendritic, delayed, stochastic CaMKII activation in behavioural time scale plasticity

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

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Dendritic excitations govern back-propagation via a spike-rate accelerometer

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

Published: Feb. 4, 2025

Dendrites on neurons support electrical excitations, but the computational significance of these events is not well understood. We developed molecular, optical, and tools for all-optical electrophysiology in dendrites. mapped sub-millisecond voltage dynamics throughout dendritic trees CA1 pyramidal under diverse optogenetic synaptic stimulus patterns, acute brain slices. Our data show history-dependent spike back-propagation distal dendrites, driven by locally generated Na+ spikes (dSpikes). Dendritic depolarization created a transient window dSpike propagation, opened A-type KV channel inactivation, closed slow NaV inactivation. Collisions dSpikes with inputs triggered calcium N-methyl-D-aspartate receptor (NMDAR)-dependent plateau potentials accompanying complex at soma. This hierarchical ion network acts as spike-rate accelerometer, providing an intuitive picture connecting biophysics to associative plasticity rules. Neural mechanisms mediating information flow processing dendrites are fully Here authors techniques map bioelectrical excitations slices mouse tissue. They holistic roles back-propagation.

Language: Английский

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Synaptic plasticity rules driving representational shifting in the hippocampus

Nature Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Language: Английский

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Building transformers from neurons and astrocytes

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(34)

Published: Aug. 14, 2023

Glial cells account for between 50% and 90% of all human brain cells, serve a variety important developmental, structural, metabolic functions. Recent experimental efforts suggest that astrocytes, type glial cell, are also directly involved in core cognitive processes such as learning memory. While it is well established astrocytes neurons connected to one another feedback loops across many timescales spatial scales, there gap understanding the computational role neuron-astrocyte interactions. To help bridge this gap, we draw on recent advances AI astrocyte imaging technology. In particular, show networks can naturally perform computation Transformer, particularly successful architecture. doing so, provide concrete, normative, experimentally testable communication. Because Transformers so wide task domains, language, vision, audition, our analysis may explain ubiquity, flexibility, power brain's networks.

Language: Английский

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A critical role for CaMKII in behavioral timescale synaptic plasticity in hippocampal CA1 pyramidal neurons

Science Advances, Journal Year: 2023, Volume and Issue: 9(36)

Published: Sept. 6, 2023

Behavioral timescale synaptic plasticity (BTSP) is a type of non-Hebbian reported to underlie place field formation. Despite this important function, the molecular mechanisms underlying BTSP are poorly understood. The α-calcium-calmodulin-dependent protein kinase II (αCaMKII) activated by transmission–mediated calcium influx, and its subsequent phosphorylation central plasticity. Because activity αCaMKII known outlast event triggering phosphorylation, we hypothesized that it could mediate extended BTSP. To examine role in BTSP, performed whole-cell vivo vitro recordings CA1 pyramidal neurons from mice engineered with point mutation at autophosphorylation site (T286A) causing accelerated signaling kinetics. Here, demonstrate profound deficit plasticity, strongly suggesting required for This study elucidates part mechanism provides insight into function cell formation ultimately learning memory.

Language: Английский

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Synaptic Basis of Behavioral Timescale Plasticity

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

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Mechanisms of memory-supporting neuronal dynamics in hippocampal area CA3

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

Published: Oct. 1, 2024

Language: Английский

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Structures of channelrhodopsin paralogs in peptidiscs explain their contrasting K+ and Na+ selectivities

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 20, 2023

Kalium channelrhodopsin 1 from Hyphochytrium catenoides (HcKCR1) is a light-gated channel used for optogenetic silencing of mammalian neurons. It selects K

Language: Английский

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