the temporoammonic (TA) input to CA1 synapse is hyperexcitable in MeCP2 -/Y mice
Bibliographic record
Abstract
The temporoammonic (TA) pathway provides input directly from layer III of the entorhinal cortex (ECIII) to the distal dendrites of CA1 pyramidal cells in the stratum lacunosum-moleculare (SLM) of the hippocampus. The TA synapse influences the firing of CA1 pyramidal neurons and modulates the flow of information to the hippocampus. Neurons in ECIII are degenerated in Rett Syndrome (RTT), thus the aim of this study is to investigate how the presence of the MeCP2 mutation alters properties of the TA-CA1 synapse using electrophysiological characterization of synaptic and network connectivity. Electrophysiological neuronal properties were assessed by making whole-cell patch clamp recordings. The SLM neurons in Mecp2-/Y mice were found to be hyperexcitable showing increased action potential firing rate, with a significantly larger sag potential and post inhibitory rebound potential observed compared to matched wild-types. Additionally, evoked EPSCs of CA1 pyramidal neurons were significantly larger when the TA-CA1 pathway was stimulated, with no change in evoked IPSCs compared to wild-types. Moreover, the reversal potential for GABA (EGABA) was measured using a high intracellular chloride concentration (30mM) and found to be depolarized compared to wild-types controls. Finally, to assess network connectivity we examined hippocampal long-term potentiation induction and paired pulse ratio which were both found to be unaffected in TA-CA1 pathway in the MeCP2-/Y mouse. Taken together, the data demonstrates increased intrinsic excitability of the CA1 pyramidal neurons, revealing a potential mechanism of changes in GABA activity and provide preliminary evidence suggesting that targeting this phenotype may rescue neuronal abnormality and disease progression.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".