Dissecting Cortical Dopamine D2 Receptor: from mapping to circuit-specific function
Bibliographic record
Abstract
The dopamine D2 receptor (D2R), as a critical mediator of dopamine actions, is involved in a variety of central nervous system functions ranging from motor control to complex cognitive processes. In line with these multiple functions, D2Rs are implicated in the pathophysiology of movement and psychiatric disorders, such as Parkinson’s disease and schizophrenia, and are a major target for several pharmacological treatments. While the general behavioral contributions of striatal D2R are well understood, the neuroanatomical correlation of cortical D2R functions are operationally biased by limitation of experimental approaches such as low mRNA expression, ligand selectivity, or based on the inefficiency of gene reporter systems. In this work we first established a complete cortex-wide map of D2R expressing cells by using a transgenic mouse carrying a high sensitivity digital reporter for D2R expression. We uncovered several previously uncharacterized neuronal clusters expressing D2R in cortical regions and their cell-type specificity which may provide valuable information for the in vivo study of cortical D2Rs and their impact in dopamine associated disorders. Second, we focused on the role of D2R in the medial prefrontal cortex (mPFC), a key region known to play a role in cognitive functions that contribute to appropriate goal-directed and flexible behaviour. By using amphetamine administration to model a classic pharmacological representation of psychomotor agitation, we discovered an unexpected involvement of mPFC D2R regulation on motor behavioral outcomes. This study highlights the possible implication of D2R regulation in the mPFC in the development of neuropsychiatric disorders and in the effectiveness of antipsychotics to treat positive symptoms in schizophrenia. Finally, we describe how selective silencing of D2R in the mPFC revealed the engagement of a top-down prefronto-striatal network that controls the regulation of striatal cholinergic microcircuitry and leads to the suppression of inappropriate psychomotor responses. Overall, this thesis sheds light on improved distinction of regional and cell-type specific D2R distribution and function that may provide better understanding of D2R impact contributing to the diverse symptomatology of neuropsychiatric disorders. We also provide evidence of the utility of precision targeted strategies using intersectional CRISPR/Cas9 methodology for the interrogation of circuit specific functions of D2R.
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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".