Spine loss in depression impairs dendritic signal integration in human cortical microcircuit models
Bibliographic record
Abstract
Major depressive disorder (depression) is associated with altered dendritic structure and function of cortical pyramidal neurons, due to decreased inhibition from somatostatin (SST) interneurons and loss of spines and associated synapses, as indicated in postmortem human studies. Dendrites mediate signal processing through synaptic integration and nonlinear properties including backpropagating action potentials and dendritic Na + spikes that enhance the neuron's computational power. However, it is currently unclear how depression-related dendritic changes impact signal integration. Here, we integrated human neuronal data of active dendritic properties and spine loss in depression into detailed computational models of human cortical microcircuits. We show that spine loss dampens signal response, worsening signal detection impairment than due to reduced SST interneuron inhibition alone. Furthermore, altered intrinsic properties due to spine loss abolished nonlinear dendritic signal integration and impaired recurrent microcircuit activity. Our study mechanistically links cellular changes in depression to impaired dendritic processing in human cortical microcircuits.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".