Synaptic plasticity in human thalamocortical assembloids

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 1, 2024

SUMMARY Synaptic plasticities, such as long-term potentiation (LTP) and depression (LTD), tune synaptic efficacy are essential for learning memory. Current studies of plasticity in humans limited by a lack adequate human models. Here, we modeled the thalamocortical system fusing induced pluripotent stem cell–derived thalamic cortical organoids. Single-nucleus RNA-sequencing revealed that most cells mature organoids were glutamatergic neurons. When fused to form assembloids, formed reciprocal long-range axonal projections synapses detectable light electron microscopy, respectively. Using whole-cell patch-clamp electrophysiology two-photon imaging, characterized transmission. Thalamocortical corticothalamic displayed short-term analogous animal LTP LTD reliably at both synapses; however, their mechanisms differed from those previously described rodents. Thus, assembloids provide model exploring circuits. Highlights Human consist mostly projection synapses. Synapses functional undergo resembling Long-term reveal distinct eTOC often used diseases with pathology; few have examined function via single-cell or single-synapse recordings. Patton et al. into examine transmission short- GRAPHICAL ABSTRACT

Язык: Английский

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Dual transcranial electromagnetic stimulation of the precuneus-hippocampus network boosts human long-term memory

Опубликована: Фев. 13, 2025

Non-invasive brain stimulation techniques have the potential to improve memory functions. However, results so far been relatively modest and time-consuming. Here, we implemented a novel 3-minute combination of personalized repetitive transcranial magnetic (intermittent theta burst-iTBS) coupled with simultaneous application gamma alternating current (γtACS) over precuneus, area connected hippocampus, modulate long term in healthy subjects. Only dual electromagnetic precuneus produced consistent increase long-term associative as compared iTBS alone sham conditions sample volunteers. The effects were replicated another independent sample, which increased was retained for up one week. Moreover, oscillations precuneus-hippocampus functional connectivity through white matter tracts linking temporal lobe. These findings show that may lead neuronal assemblies state favorable enhance plasticity identify key involved formation. Personalized network represent new powerful approach enhancing functions several clinical conditions.

Язык: Английский

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Dual transcranial electromagnetic stimulation of the precuneus-hippocampus network boosts human long-term memory

Опубликована: Фев. 13, 2025

Non-invasive brain stimulation techniques have the potential to improve memory functions. However, results so far been relatively modest and time-consuming. Here, we implemented a novel 3-minute combination of personalized repetitive transcranial magnetic (intermittent theta burst-iTBS) coupled with simultaneous application gamma alternating current (γtACS) over precuneus, area connected hippocampus, modulate long term in healthy subjects. Only dual electromagnetic precuneus produced consistent increase long-term associative as compared iTBS alone sham conditions sample volunteers. The effects were replicated another independent sample, which increased was retained for up one week. Moreover, oscillations precuneus-hippocampus functional connectivity through white matter tracts linking temporal lobe. These findings show that may lead neuronal assemblies state favorable enhance plasticity identify key involved formation. Personalized network represent new powerful approach enhancing functions several clinical conditions.

Язык: Английский

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Neocortical Layer-5 tLTD Relies on Non-Ionotropic Presynaptic NMDA Receptor Signaling

Опубликована: Апрель 8, 2025

In the textbook view, NMDA receptors (NMDARs) act as coincidence detectors in Hebbian plasticity by fluxing Ca 2+ when simultaneously depolarized and glutamate bound. detection requires that NMDARs be located postsynaptically, but enigmatic presynaptic (preNMDARs) also exist. It is known preNMDARs regulate neurotransmitter release, precisely how remains poorly understood. Emerging evidence suggest can signal non-ionotropically, without need for flux. At synapses between developing visual cortex layer-5 (L5) pyramidal cells (PCs), rely on Mg Rab3-interacting molecule 1αβ (RIM1αβ) to evoked release during periods of high-frequency firing, they non-ionotropically via c-Jun N-terminal kinase 2 (JNK2) spontaneous regardless frequency. same synapses, timing- dependent long-term depression (tLTD) depends not We therefore tested if tLTD relies non-ionotropic preNMDAR signaling. found at L5 PC→PC was abolished pre- postsynaptic NMDAR deletion, cementing view preNMDARs. agreement with signaling, prevailed after channel pore blockade MK-801, unlike tLTP. Homozygous RIM1αβ deletion did affect tLTD, wash-in JNK2 blocker SP600125 tLTD. Consistent a JNK2, peptide blocking interaction Syntaxin-1a (STX1a) loaded Finally, low-frequency blocked nor 7-CK, non-competitive antagonist co-agonist site. conclude neocortical signaling JNK2/STX1a. Our study brings closure long-standing controversy surrounding highlights ionotropic needs reassessed.

Язык: Английский

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Latent mechanisms of plasticity are upregulated during sleep

Current Opinion in Neurobiology, Год журнала: 2025, Номер 93, С. 103029 - 103029

Опубликована: Апрель 22, 2025

Язык: Английский

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Coincidence detection between apical and basal dendrites drives STDP in cerebellar Golgi cells

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Май 12, 2025

Cerebellar Golgi cells (GoCs), segregate parallel fiber (pf), and mossy (mf) inputs on apical basal dendrites. Computational modeling predicted that this anatomical arrangement, coupled with a specific ionic channel localization, could be instrumental to drive STDP at mf-GoC synapses. Here, we test hypothesis GoC patch-clamp recordings in acute mouse cerebellar slices. Repeated mf-pf pairing the theta-band within ± 50 ms time window induces anti-symmetric Hebbian-STDP, spike-timing long-term potentiation or depression (st-LTP st-LTD) occurring when action potentials (APs) elicited by pf stimulation follow precede activation of mf synapses, respectively. Mf-GoC induction requires AP backpropagation from dendrites, NMDA receptor intracellular calcium changes. Importantly, is inverted inhibitory control. Thus, experimental evidence confirms extends model predictions suggesting can bind molecular layer granular activity, regulating computation learning.

Язык: Английский

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Neocortical Layer-5 tLTD Relies on Non-Ionotropic Presynaptic NMDA Receptor Signaling

Опубликована: Май 23, 2025

Abstract In the textbook view, NMDA receptors (NMDARs) act as coincidence detectors in Hebbian plasticity by fluxing Ca2+ when simultaneously depolarized and glutamate bound. detection requires that NMDARs be located postsynaptically, but enigmatic presynaptic (preNMDARs) also exist. It is known preNMDARs regulate neurotransmitter release, precisely how remains poorly understood. Emerging evidence suggest can signal non-ionotropically, without need for flux. At synapses between developing visual cortex layer-5 (L5) pyramidal cells (PCs), rely on Mg2+ Rab3-interacting molecule 1αβ (RIM1αβ) to evoked release during periods of high-frequency firing, they non-ionotropically via c-Jun N-terminal kinase 2 (JNK2) spontaneous regardless frequency. same synapses, timing-dependent long-term depression (tLTD) depends not We therefore tested if tLTD relies non-ionotropic preNMDAR signaling. found at L5 PC→PC was abolished pre- postsynaptic NMDAR deletion, cementing view preNMDARs. agreement with signaling, prevailed after channel pore blockade MK-801, unlike tLTP. Homozygous RIM1αβ deletion did affect tLTD, wash-in JNK2 blocker SP600125 tLTD. Consistent a JNK2, peptide blocking interaction Syntaxin-1a (STX1a) loaded Finally, low-frequency blocked nor 7-CK, non-competitive antagonist co-agonist site. conclude neocortical signaling JNK2/STX1a. Our study brings closure long-standing controversy surrounding highlights ionotropic needs reassessed.

Язык: Английский

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Anti-Hebbian plasticity drives sequence learning in striatum

Communications Biology, Год журнала: 2024, Номер 7(1)

Опубликована: Май 9, 2024

Spatio-temporal activity patterns have been observed in a variety of brain areas spontaneous activity, prior to or during action, response stimuli. Biological mechanisms endowing neurons with the ability distinguish between different sequences remain largely unknown. Learning spikes raises multiple challenges, such as maintaining memory spike history and discriminating partially overlapping sequences. Here, we show that anti-Hebbian spike-timing dependent plasticity (STDP), at cortico-striatal synapses, can naturally lead learning We design spiking model striatal output neuron receiving defined sequential input from fixed set cortical neurons. use simple synaptic rule combines STDP non-associative potentiation for subset presented called rewarded patterns. study discriminate non-rewarded by firing only after presentation pattern. In particular, two biological properties networks, latency collateral inhibition, contribute an increase accuracy, allowing better discrimination These results suggest may serve substrate spikes.

Язык: 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, Год журнала: 2023, Номер 99(8), С. 254 - 305

Опубликована: Окт. 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.

Язык: Английский

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The role of NMDA receptors in memory and prediction in cultured neural networks

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 1, 2024

Abstract Memory has been extensively studied at the behavioural as well cellular level. Spike timing dependent plasticity (STDP) is associated with N-methyl-D-aspartate (NMDA) receptor activation and widely accepted to be essential for long-term memory. However, experimental evidence remains sparse, probably due required complex combination of functional readouts. Recent work showed that in-vitro cortical networks memorize predict inputs. The initial dependency prediction on short-term memory decreased during formation traces. Here, we stimulated investigate under control conditions, or NMDA block. anatagonist 2-amino-5-phosphonovaleric acid (APV) a concentration did not significantly reduce network excitability, but impede trace formation. In APV-treated cultures stimuli persisted, they were still able predict. contrast cultures, remained fully This confirms traces supports notion that, learn stimulus, starts contribute their predictive capability.

Язык: Английский

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