ISDN2014_0302: Depolarizing GABAA transmission sets dendritic spine density in the developing organotypic hippocampal slice
Bibliographic record
Abstract
GABA is the main inhibitory neurotransmitter in the mature brain. However, it has the unusual property of depolarizing, or exciting, neurons in the immature brain. This feature of the immature nervous system is important for several developmental processes, including neural circuit formation. During the phase when GABA is depolarizing, dendritic spines, the specialized sites that harbour the majority of glutamatergic synapses, are forming and maturing. To assess whether early GABAA neurotransmission influences the formation of glutamatergic synapses, we pharmacologically modulated GABAA transmission while monitoring dendritic spine formation on CA1 neurons in mouse organotypic hippocampal slices. Similar to previous findings, inhibiting mature GABAA transmission for 48 h with gabazine or bicuculline in slices grown for 5 days in vitro (DIV) caused robust spine loss. However, the same manipulations in younger slices (3DIV) caused a significant increase in spine density. Conversely, driving GABAA transmission at 3DIV caused a decrease in spine density. To test whether GABA is depolarizing at this early stage, we assessed ECl and expression of the K+/Cl− cotransporter KCC2, which is responsible for establishing the mature Cl− gradient in neurons and shifting GABA from depolarizing to hyperpolarizing. The period over which the switch in the effect of GABAA antagonists occurred (3–7DIV) was paralleled by a marked increase in KCC2 expression and a shift in ECl from depolarized to hyperpolarized with respect to resting membrane potential. Importantly, GABAA blockade did not itself alter KCC2 levels. Finally, we found that prematurely reducing intracellular chloride with bumetanide inhibited the ability of GABAA blockade to increase dendritic spine number, while not having any baseline effect alone. This indicates that altering depolarizing GABAA transmission changes spine number, but altering hyperpolarizing GABAA transmission does not. Together, our findings suggest an important role of depolarizing GABAA transmission in controlling dendritic spine formation during early postnatal development.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.015 | 0.008 |
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".