Cortico-cortical feedback engages active dendrites in visual cortex

Nature, Journal Year: 2023, Volume and Issue: 617(7962), P. 769 - 776

Published: May 3, 2023

Abstract Sensory processing in the neocortex requires both feedforward and feedback information flow between cortical areas 1 . In processing, higher-level representations provide contextual to lower levels, facilitate perceptual functions such as contour integration figure–ground segmentation 2,3 However, we have limited understanding of circuit cellular mechanisms that mediate influence. Here use long-range all-optical connectivity mapping mice show influence from lateromedial higher visual area (LM) primary cortex (V1) is spatially organized. When source target represent same space, relatively suppressive. By contrast, when offset facilitating. Two-photon calcium imaging data this facilitating nonlinearly integrated apical tuft dendrites V1 pyramidal neurons: retinotopically (surround) stimuli drive local dendritic signals indicative regenerative events, two-photon optogenetic activation LM neurons projecting identified feedback-recipient spines can similar branch-specific signals. Our results how neocortical nonlinear together form a substrate support predictive cooperative interactions.

Language: Английский

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Activity-dependent compartmentalization of dendritic mitochondria morphology through local regulation of fusion-fission balance in neurons in vivo

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

Published: March 8, 2024

Abstract Neuronal mitochondria play important roles beyond ATP generation, including Ca 2+ uptake, and therefore have instructive in synaptic function neuronal response properties. Mitochondrial morphology differs significantly between the axon dendrites of a given subtype, but CA1 pyramidal neurons (PNs) hippocampus, within dendritic arbor also display remarkable degree subcellular, layer-specific compartmentalization. In these neurons, ranges from highly fused elongated apical tuft, to more fragmented oblique basal compartments, thus occupy smaller fraction volume than tuft. However, molecular mechanisms underlying this striking subcellular compartmentalization are unknown, precluding assessment its impact on function. Here, we demonstrate that compartment-specific requires activity-dependent, Camkk2-dependent activation AMPK ability phosphorylate two direct effectors: pro-fission Drp1 receptor Mff recently identified anti-fusion, Opa1-inhibiting protein, Mtfr1l. Our study uncovers signaling pathway mitochondrial vivo through spatially precise activity-dependent regulation fission/fusion balance.

Language: Английский

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Metal Ion Signaling in Biomedicine

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

Complex multicellular organisms are composed of distinct tissues involving specialized cells that can perform specific functions, making such life forms possible. Species defined by their genomes, and differences between individuals within a given species directly result from variations in genetic codes. While alterations give rise to disease-causing acquisitions cell identities, it is now well-established biochemical imbalances also lead cellular dysfunction diseases. Specifically, nongenetic chemical events orchestrate metabolism transcriptional programs govern functional identity. Thus, signaling, which broadly defines the conversion extracellular signals into intracellular changes, contribute acquisition diseased states. Metal ions exhibit unique properties be exploited cell. For instance, metal maintain ionic balance cell, coordinate amino acid residues or nucleobases altering folding function biomolecules, catalyze reactions. metals essential signaling effectors normal physiology disease. Deciphering ion challenging endeavor illuminate pathways targeted for therapeutic intervention. Here, we review key processes where play roles describe how targeting has been instrumental dissecting biochemistry this led development effective strategies.

Language: Английский

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Enhanced mitochondrial fusion during a critical period of synaptic plasticity in adult-born neurons

Neuron, Journal Year: 2024, Volume and Issue: 112(12), P. 1997 - 2014.e6

Published: April 5, 2024

Integration of new neurons into adult hippocampal circuits is a process coordinated by local and long-range synaptic inputs. To achieve stable integration uniquely contribute to function, immature are endowed with critical period heightened plasticity, yet it remains unclear which mechanisms sustain this form plasticity during neuronal maturation. We found that as enter their period, transient surge in fusion dynamics stabilizes elongated mitochondrial morphologies dendrites fuel plasticity. Conditional ablation prevent elongation selectively impaired spine potentiation, disrupting competition for circuit integration, ultimately leading decreased survival. Despite profuse fragmentation, manipulation was sufficient restore survival but left poorly responsive experience at the level. Thus, enabling facilitates remodeling adult-born neurons.

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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Sub-cellular population imaging tools reveal stable apical dendrites in hippocampal area CA3

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

Published: Jan. 28, 2025

Apical and basal dendrites of pyramidal neurons receive anatomically functionally distinct inputs, implying compartment-level functional diversity during behavior. To test this, we imaged in vivo calcium signals from soma, apical dendrites, mouse hippocampal CA3 head-fixed navigation. capture compartment-specific population dynamics, developed computational tools to automatically segment extract accurate fluorescence traces densely labeled neurons. We validated the method on sparsely preparations synthetic data, predicting an optimal labeling density for high experimental throughput analytical accuracy. Our detected rapid, local dendritic activity. Dendrites showed robust spatial tuning, similar soma but with higher activity rates. Across days, remained more stable outperformed decoding animal's position. Thus, population-level differences may reflect input-output functions computations CA3. These will facilitate future studies mapping sub-cellular their relation The authors develop analysis package characterizing neural using optical imaging show that are representations than area

Language: Английский

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Mitochondrial complexity is regulated at ER-mitochondria contact sites via PDZD8-FKBP8 tethering

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

Published: April 17, 2025

Mitochondria-ER membrane contact sites (MERCS) represent a fundamental ultrastructural feature underlying unique biochemistry and physiology in eukaryotic cells. The ER protein PDZD8 is required for the formation of MERCS many cell types, however, its tethering partner on outer mitochondrial (OMM) currently unknown. Here we identify OMM FKBP8 as using combination unbiased proximity proteomics, CRISPR-Cas9 endogenous tagging, Cryo-electron tomography, correlative light-electron microscopy. Single molecule tracking reveals highly dynamic diffusion properties along with significant pauses captures at MERCS. Overexpression sufficient to narrow ER-OMM distance, whereas independent versus combined deletions these two proteins demonstrate their interdependence formation. Furthermore, enhances complexity FKBP8-dependent manner. Our results novel ER-mitochondria complex that regulates morphology mammalian

Language: Английский

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Decreasing pdzd8-mediated mito–ER contacts improves organismal fitness and mitigates Aβ₄₂toxicity

Life Science Alliance, Journal Year: 2022, Volume and Issue: 5(11), P. e202201531 - e202201531

Published: July 13, 2022

Mitochondria-ER contact sites (MERCs) orchestrate many important cellular functions including regulating mitochondrial quality control through mitophagy and mediating calcium uptake. Here, we identify functionally characterize the Drosophila ortholog of recently identified mammalian MERC protein, Pdzd8. We find that reducing pdzd8-mediated MERCs in neurons slows age-associated decline locomotor activity increases lifespan Drosophila. The protective effects pdzd8 knockdown correlate with an increase mitophagy, suggesting increased turnover may support healthy aging neurons. In contrast, increasing by expressing a constitutive, synthetic ER–mitochondria tether disrupts transport synapse formation, accelerates age-related locomotion, reduces lifespan. Although depletion prolongs survival flies fed toxins, it is also sufficient to rescue defects fly model Alzheimer’s disease Amyloid β 42 (Aβ ). Together, our results provide first vivo evidence mediated tethering protein play critical role regulation neuronal homeostasis.

Language: Английский

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Dendritic Compartmentalization of Learning-Related Plasticity

eNeuro, Journal Year: 2022, Volume and Issue: 9(3), P. ENEURO.0060 - 22.2022

Published: May 1, 2022

The dendrites of cortical pyramidal neurons receive synaptic inputs from different pathways that are organized according to their laminar target. This architectural scheme provides with a spatial mechanism separate information, which may support neural flexibility required during learning. Here, we investigated layer-specific plasticity sensory encoding following learning by recording two dendritic compartments, tuft and basal dendrites, layer 2/3 (L2/3) in the auditory cortex mice. Following fear conditioning, auditory-evoked Ca 2+ responses were enhanced tuft, but not basal, leading increased somatic action potential output. is direct contrast long held (and debated) hypothesis that, despite extensive arbors, function as simple one-compartment model. Two computational models varying complexity based on experimental data illustrated this learning-related increase can account for changes Taken together, illustrate do single compartment, compartmentalization act power neurons.

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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