Anterograde Trophic Mechanisms Participate in Pattern Formation in the Striatum: A Role for BDNF in Glutamatergic Afferents
Bibliographic record
Abstract
Increasing evidence suggests that neurotransmitters cooperate with growth factors to promote cell survival in the developing CNS (Aloyz et al., 1999; Blum and Konnerth, 2005). In the striatum, retrograde trophic support from targets, including the ventral midbrain, is important for survival of neurons during postnatal apoptosis (van der Kooy 1996). We hypothesized that anterograde trophic support to the striatum from glutamatergic systems is also an important determinant of neuronal survival during the apoptosis period. We used the glutamatergic thalamostriatal system (TS) arising from the parafascicular (PF) nucleus as a model. We proposed that anterograde transport of the neurotrophin brainderived neurotrophic factor (BDNF), occurs in the developing TS system, and cooperates with glutamate to rescue striatal neurons from apoptosis. We demonstrate that early striatal deafferentation by lesioning of the rat PF nucleus at postnatal day 2 (P2) results in: 1) 30% loss of neostriatum neurons by P35 when quantified on Nissl stains using unbiased streology; 2) enhanced apoptosis in the striatum during the first two postnatal weeks measured using Western blots for activated caspase-3; 3) and marked reduction in striatal BDNF content on protein biochemistry. In ongoing work, neuronal loss after P2 PF lesions is markedly reduced by striatal injection of BDNF containing spheres during the first postnatal week. Anterograde trophic mechanisms play an important role in determining the final complement of striatal neurons. We provide novel evidence indicating that BDNF serves as an “anterophin” in developing glutamatergic striatal afferents, and may cooperate with glutamate to promote activity dependent rescue of striatal neurons, thus matching neuronal number with afferent density.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".