Distinct place cell dynamics in CA1 and CA3 encode experience in new environments

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: May 20, 2021

Abstract When exploring new environments animals form spatial memories that are updated with experience and retrieved upon re-exposure to the same environment. The hippocampus is thought support these memory processes, but how this achieved by different subnetworks such as CA1 CA3 remains unclear. To understand hippocampal representations emerge evolve during familiarization, we performed 2-photon calcium imaging in mice running virtual compared trial-to-trial dynamics of place cells over days. We find fields rapidly tend shift backwards from remap environment a day later. In contrast, gradually show more stable day-to-day dynamics. These results reflect roles processing familiarization constrain potential mechanisms them.

Language: Английский

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Fos ensembles encode and shape stable spatial maps in the hippocampus

Nature, Journal Year: 2022, Volume and Issue: 609(7926), P. 327 - 334

Published: Aug. 24, 2022

Abstract In the hippocampus, spatial maps are formed by place cells while contextual memories thought to be encoded as engrams 1–6 . Engrams typically identified expression of immediate early gene Fos , but little is known about neural activity patterns that drive, and shaped by, in behaving animals 7–10 Thus, it unclear whether Fos-expressing hippocampal neurons also encode correlates with affects specific features code 11 Here we measured CA1 calcium imaging monitoring induction mice performing a hippocampus-dependent learning task virtual reality. We find high form ensembles highly correlated activity, exhibit reliable fields evenly tile environment have more stable tuning across days than nearby non-Fos-induced cells. Comparing neighbouring without function using sparse genetic loss-of-function approach, disrupted less decreased selectivity lower across-day stability. Our results demonstrate Fos-induced contribute codes encoding accurate, spatially uniform itself has causal role shaping these codes. may therefore link two key aspects function: for underlie cognitive maps.

Language: Английский

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Compartment-specific tuning of dendritic feature selectivity by intracellular Ca ²⁺ release

Science, Journal Year: 2022, Volume and Issue: 375(6586)

Published: March 17, 2022

Dendritic calcium signaling is central to neural plasticity mechanisms that allow animals adapt the environment. Intracellular release (ICR) from endoplasmic reticulum has long been thought shape these mechanisms. However, ICR not investigated in mammalian neurons vivo. We combined electroporation of single CA1 pyramidal neurons, simultaneous imaging dendritic and somatic activity during spatial navigation, optogenetic place field induction, acute genetic augmentation cytosolic impact reveal supports establishment feature selectivity shapes integrative properties determining output-level receptive fields. This role for was more prominent apical than basal dendrites. Thus, cooperates with circuit-level architecture vivo promote emergence behaviorally relevant a compartment-specific manner.

Language: Английский

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Signatures of rapid plasticity in hippocampal CA1 representations during novel experiences

Neuron, Journal Year: 2022, Volume and Issue: 110(12), P. 1978 - 1992.e6

Published: April 20, 2022

Language: Английский

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All-optical physiology resolves a synaptic basis for behavioral timescale plasticity

Cell, Journal Year: 2023, Volume and Issue: 186(3), P. 543 - 559.e19

Published: Jan. 19, 2023

Learning has been associated with modifications of synaptic and circuit properties, but the precise changes storing information in mammals have remained largely unclear. We combined genetically targeted voltage imaging optogenetic activation silencing pre- post-synaptic neurons to study mechanisms underlying hippocampal behavioral timescale plasticity. In mice navigating a virtual-reality environment, individual CA1 cells at specific places induced stable representations these cells. Optical elicitation, recording, modulation transmission behaving revealed that activity presynaptic CA2/3 was required for induction plasticity and, furthermore, during place fields single cells, input from onto same potentiated. These results reveal implementation define methodology resolve learning memory mammals.

Language: Английский

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Hippocampal astrocytes encode reward location

Nature, Journal Year: 2022, Volume and Issue: 609(7928), P. 772 - 778

Published: Aug. 31, 2022

Language: Английский

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The Neuropsychology of Anxiety

Oxford University Press eBooks, Journal Year: 2024, Volume and Issue: unknown

Published: May 7, 2024

Abstract The Neuropsychology of Anxiety first appeared in 1982 as the volume Oxford Psychology Series, and it quickly established itself classic work on subject. It second edition (appearing 2000) have been cited at a steadily increasing rate passing 500/year 2017. field has continued to expand last quarter century necessitating this third edition. This completely updated revised (with many figures converted colour) retains original core concepts while expanding often simplifying details. includes new chapter prefrontal cortex, which integrates frontal hippocampal views anxiety an extensively modified personality providing basis for further developments Reinforcement Sensitivity Theory. book is essential postgraduate students researchers experimental psychology neuroscience, well all clinical psychologists psychiatrists.

Language: Английский

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Associative and predictive hippocampal codes support memory-guided behaviors

Science, Journal Year: 2023, Volume and Issue: 382(6668)

Published: Oct. 19, 2023

Episodic memory involves learning and recalling associations between items their spatiotemporal context. Those memories can be further used to generate internal models of the world that enable predictions made. The mechanisms support these associative predictive aspects are not yet understood. In this study, we an optogenetic manipulation perturb sequential structure, but global network dynamics, place cells as rats traversed specific spatial trajectories. This perturbation abolished replay those trajectories development representations, leading impaired new optimal during memory-guided navigation. However, cell assembly reactivation reward-context were unaffected. Our results show a mechanistic dissociation two complementary hippocampal codes: code (through coactivity) sequences).

Language: Английский

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Pathological BBB Crossing Melanin-Like Nanoparticles as Metal-Ion Chelators and Neuroinflammation Regulators against Alzheimer’s Disease

Research, Journal Year: 2023, Volume and Issue: 6

Published: Jan. 1, 2023

Inflammatory responses, manifested in excessive oxidative stress and microglia overactivation, together with metal ion-triggered amyloid-beta (Aβ) deposition, are critical hallmarks of Alzheimer’s disease (AD). The intricate pathogenesis causes severe impairment neurons, which, turn, exacerbates Aβ aggregation facilitates AD progression. Herein, multifunctional melanin-like ion chelators neuroinflammation regulators (named PDA@K) were constructed for targeted treatment AD. In this platform, intrinsically bioactive material polydopamine nanoparticles (PDA) potent chelating ROS scavenging effects decorated the KLVFF peptide, endowing system capacity enhanced pathological blood–brain barrier (BBB) crossing lesion site accumulation via hitchhiking. vitro vivo experiment revealed that PDA@K had high affinity toward able to hitch a ride on achieve increased BBB crossing. engineered effectively mitigated aggregate alleviated neuroinflammation. modulated inflammatory microenvironment by promoted microglial polarization M2-like phenotype, which restored their functions neuron care plaque removal. After 3-week PDA@K, spatial learning memory deficit as well neurologic changes FAD 4T transgenic mice largely rescued. Transcriptomics analysis further therapeutic mechanism PDA@K. Our study provided an appealing paradigm directly utilizing intrinsic properties nanomaterials therapeutics instead just using them nanocarriers, widen application therapy.

Language: Английский

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Mannose-Integrated Nanoparticle Hitchhike Glucose Transporter 1 Recycling to Overcome Various Barriers of Oral Delivery for Alzheimer’s Disease Therapy

ACS Nano, Journal Year: 2024, Volume and Issue: 18(4), P. 3234 - 3250

Published: Jan. 12, 2024

A brain-targeting nanodelivery system has been a hot topic and undergone rapid progression. However, due to various obstacles such as the intestinal epithelial barrier (IEB) blood-brain (BBB), few nanocarriers can achieve through oral administration. Herein, an intelligent nanoparticle (FTY@Man NP) constructed from PLGA-PEG skeleton loaded with fingolimod (FTY) externally modified mannose was designed in combination glucose control strategy for multitarget treatment of Alzheimer's disease (AD). The hydrophilic electronegative properties facilitated its facile penetration mucus barrier, while ligand conferred IEB targeting abilities nanoparticle. Subsequently, glycemic allowed mannose-integrated hitchhike transporter 1 (GLUT1) circulation across BBB. Finally, released FTY modulated polarity microglia pro-inflammatory M1 anti-inflammatory M2 normalized activated astrocyte, enhancing clearance toxic protein Amyloid-β (Aβ) alleviating oxidative stress neuroinflammation. Notably, both vitro vivo results have consistently demonstrated that administration FTY@Man NP could effectively traverse multiple barriers, thereby exerting significant therapeutic effects. This breakthrough holds promise realizing highly effective orally administered AD.

Language: Английский

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