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Coarse-Grained Models for…
Microglia-mediated synaptic… ×
NATURE NEUROSCIENCE · 2024 Page 3 / 14
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Microglia-mediated synaptic pruning sculpts hippocampal circuits during postnatal development

Activity-dependent elimination of excess synapses is a defining feature of postnatal circuit refinement, yet the cellular machinery that selects which synapses to eliminate remains incompletely understood. Using longitudinal two-photon imaging of CA1 pyramidal neurons in CX3CR1-GFP mice between P15 and P30, we show that microglia engage dendritic spines tagged with complement C3[12] and engulf them through CR3-mediated phagocytosis.

Conditional ablation of microglial CR3 produced a sustained excess of weak, low-GluA1 spines, impaired LTP, and degraded spatial memory in the Morris water maze.

Excess dendritic spines formed in early life are progressively eliminated through synaptic pruning[7], leaving a sparser, more selective set of connections.

NOTE · p.3
Same critical period as Stevens '07?
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Voixes — Explain

Conditional ablation of microglial CR3 produced a 22% excess of low-GluA1 spines at P30, impaired NMDA receptor-dependent LTP, and degraded performance in the Morris water maze.

NMDA receptor-dependent LTP

Long-term potentiation that requires calcium influx through NMDA receptors. Here it's the functional read-out showing pruned circuits still strengthen normally.

GROUNDED IN
p.6, ¶4"…impaired NMDA receptor-dependent LTP…"
Fig 4bfEPSP slope vs. tetanus
+ Flashcard Ask follow-up
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MOL. PHARMACEUTICS · 2021
Molecular-Level Examination of Amorphous Solid Dispersion Dissolution
0% mastered
∇·D∇c = ∂c/∂t ⟨r²(t)⟩ = 6Dt P(t) ∝ e−t/τ UvdW = 4ε[(σ/r)¹² − (σ/r)⁶]
J. CHEM. THEORY COMP. · 2018
Calculation of Diffusion Coefficients through Coarse-Grained Simulations
42% mastered
NATURE · 2024
Universal Models for Atomistic Simulation
18% mastered
PHYS. REV. LETT. · 2022
Evolutionary ML of Physics-Based Force Fields
76% mastered
SCIENCE · 2023
Multiscale Modeling of Transport-Mediated Catalytic Reactions
31% mastered
JACS · 2020
Building Force Fields: Automatic, Systematic, Reproducible Workflows
5% mastered
QUICK GLANCE Molecular-Level Examination of Amorphous Solid Dispersion Dissolution
×
FIGURE 1 p. 2
Illustration of the atom mapping to DPD sites for FFA, IBP, CPV, SLP, and water.
polymerchainsprotonated
CPV5140
CPV4129196
SLP2060
SLP1669154
TABLE 1 p. 3
Composition and Size of the Early-Stage Dissolution Systems Studied
FIGURE 2 p. 4
Construction of the early-stage dissolution systems prior to simulation.
polymerdrugchains
CPVFFA10
CPVIBP110
SLPFFA5
SLPIBP134
TABLE 2 p. 4
Composition of the Late-Stage Dissolution Systems Containing Polymer, Drug, and Water
FIGURE 3 p. 5
Evolution of the CPV — water and SLP — water over 2 μs in early-stage runs.
FIGURE 4 p. 6
Evolution of the IBP/CPV — water and IBP/SLP — water over 2 μs.
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One of the characteristics of commodity products is that they have narrow profit margins[2]. A significant increase in profits therefore requires a reduction in production cost — most commonly approached through improvements in catalyst lifetime, monomer recovery, and the energy intensity of the polymerization step itself. Recent process-intensification work has begun to revisit the trade-offs between yield, throughput, and downstream purification.

[2]
C.E. Wilkes, J.W. Summers, C.A. Daniels, PVC Handbook. Hanser, Munich (2005). 3.
Open in browser Quick summary
QUICK SUMMARY
What this reference is about
A comprehensive reference text on the chemistry, properties and processing of PVC.
Why it is cited here
To support the claim that PVC is a commodity plastic, so products made from it carry narrow margins.
Voixes — Concepts
Complement cascade
Immune proteins repurposed to tag weak synapses
IN DECK
CR3 receptor
Microglial sensor for C3-tagged synapses
IN DECK
Synaptic pruning
Activity-dependent elimination of weak synapses
KNOWN
GluA1
AMPA-receptor subunit; spine-strength marker
NEW
CORE FRONT
Microglia
Resident immune cells of the brain
Reveal explanation
47× IN PAPER · TAP TO FLIP
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Voixes — Reader

Spine turnover was quantified from longitudinal two-photon stacks acquired every 48 h. Spines were classified as stable, gained, or eliminated across imaging sessions, then cross-referenced against complement-tagging status at each time point.

HIGHLIGHT COLOR
STICKY · YOU
Check 48 h cadence vs. spine-turnover half-life.
HIGHLIGHT
"longitudinal two-photon stacks"
Add a note…
Voixes — Reader
RESULTS · ¶ 3

We compared the predicted diffusion coefficients against the experimental values from Seki, Song, and Hills. Across the full CULGI database, agreement is within a factor of two for 84% of compounds, with the largest discrepancies occurring for ionised species at high pH.

log Dpredlog Dexp
Digitize this plot
Figure 4. Predicted vs. experimental diffusion coefficients across the CULGI database. Dashed line: y = x.

The systematic bias in the high-D regime is consistent with our prior observation that excluded-volume corrections become non-negligible above 10⁻⁹ m² s⁻¹.

Digitize plot Page 4 ×
Click anywhere on the plot to pick a data point Re-calibrate
X₁ X₂ Y₁ Y₂ 1234
Copy CSV Copy JSON
CALIBRATION VALUES
X₁ value 0
X₂ value 1
Y₁ value 0
Y₂ value 1
DATA POINTS Clear all
10.4000, 0.3472×
20.5189, 0.3819×
30.5491, 0.4745×
40.5245, 0.5000×
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Voixes — Discover
Microglia sculpt postnatal neural circuits in an activity- and complement-dependent manner
Schafer et al. · Neuron · 2012 · 4,102 citations
The classical complement cascade mediates CNS synapse elimination
Stevens et al. · Cell · 2007 · 1,284 citations
Microglia promote learning-dependent synapse formation through BDNF
Parkhurst et al. · Cell · 2013 · 2,051 citations
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MD related
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interesting
8 PAPERS · YESTERDAY
· Evolutionary machine learning of physics-based force…
· Molecular-Level Examination of Amorphous Solid Disp…
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JCTC · ARTICLE
Calculation of Diffusion Coefficients through Coarse-Grained Simulations
J. CHEM. THEORY & COMPUTATION · 2018
Calculation of Diffusion Coefficients through Coarse-Grained…
0% mastered0 in deck0 concepts
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