Influence of cortical synaptic input on striatal neuronal dendritic arborization and sensitivity to excitotoxicity in corticostriatal coculture
Bibliographic record
Abstract
Corticostriatal cocultures are utilized to recapitulate the cortex-striatum connection in vitro as a convenient model to investigate the development, function, and regulation of synapses formed between cortical and striatal neurons. However, optimization of this dissociated neuronal system to more closely reproduce in vivo circuits has not yet been explored. We studied the effect of varying the plating ratio of cortical to striatal neurons on striatal spiny projection neuron (SPN) characteristics in primary neuronal cocultures. Despite the large difference in cortical-striatal neuron ratio (1:1 vs. 1:3) at day of plating, by 18 days in vitro the difference became modest (∼25% lower cortical-striatal neuron ratio in 1:3 cocultures) and the neuronal density was lower in the 1:3 cocultures, indicating enhanced loss of striatal SPNs. Comparing SPNs in cocultures plated at a 1:1 vs. 1:3 ratio, we found that resting membrane potential, input resistance, current injection-induced action potential firing rates, and input-output curves were similar in the two conditions. However, SPNs in the cocultures plated at the lower cortical ratio exhibited reduced membrane capacitance along with significantly shorter total dendritic length, decreased dendritic complexity, and fewer excitatory synapses, consistent with their trend toward reduced miniature excitatory postsynaptic current frequency. Strikingly, the proportion of NMDA receptors found extrasynaptically in recordings from SPNs was significantly higher in the less cortical coculture. Consistently, SPNs in cocultures with reduced cortical input showed decreased basal pro-survival signaling through cAMP response element binding protein and enhanced sensitivity to NMDA-induced apoptosis. Altogether, our study indicates that abundance of cortical input regulates SPN dendritic arborization and survival/death signaling.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".