[P68]: <i>Cacna1f</i>‐mutant mouse exhibits altered synaptogenesis
Bibliographic record
Abstract
Mutations in CACNA1F, which encodes the human Cav1.4 subunit of an L-type voltage-gated calcium channel, cause incomplete Congenital Stationary Night Blindness (CSNB2). This highly variable X-linked retinal disorder is characterized by night blindness, reduced visual acuity, and an abnormal electrophysiological response in addition to secondary visual impairments. Recently we reported pronounced morphological changes in second-order neurons of the retina of a transgenic model of CSNB2 (Anon., 2005): ON-bipolar and horizontal cell processes extended distally from the outer plexiform layer, deep into the outer nuclear layer (ONL). Key pre- and post-synaptic components: bassoon, ribeye, and mGluR6 occurred only rarely in their normal location in the OPL or even ectopically in the ONL. This suggested that photoreceptor synapses either fail to develop properly, or degenerate after being formed, in the mutant retina. In the present study we attempted to distinguish between these two alternatives. We used transmission electron microscopy and immunocytochemistry to study the retinas from a mouse model of CSNB2, G305X, which we generated by targeted disruption of the Cacna1f gene. In the studies reported here, we compared synaptic structure in the outer plexiform layer (OPL) of age-matched mutant and control animals at postnatal days 10 and 14, the peak period for photoreceptor synaptogenesis in normal mice. Transmission electron microscopy indicated that presynaptic specializations of photoreceptors (cone pedicles, rod spherules, synaptic ribbons) and synaptic contacts between photoreceptors and second-order neurons (synaptic membrane specializations, invagination of postsynaptic processes) were rare, and highly abnormal when present, in the retinas of mutant compared with age-matched control animals. Immunocytochemistry for bassoon and ribeye showed reduced expression of bassoon at P10 and P14 and the presence of ribeye in the ONL at P14. Additionally, staining for PKCα and calbindin at P14 showed the extension of bipolar and horizontal-cell processes into the ONL respectively. These observations show that normal photoreceptor synapses fail to develop, rather than first develop and subsequently degenerate, in the Cacna1f-mutant retina. Therefore, these results suggest a key role for Cav1.4 in photoreceptor synaptogenesis in the mouse retina, and potentially provide specific clues to the functional defect of the retina in some CSNB2 patients. Supported by FFB-Canada and CIHR.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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".