Research paperBregma, lambda and the interaural midpoint in stereotaxic surgery with rats of different sex, strain and weight
Abstract
Craniometric and stereotaxic data from rats of different sex, strain and weight were compared. It was found that stereotaxic atlases can be used with rats of different sex and strain provided that the weights of the rats conform to those used in the reference atlas. If rats of different weights are used, greater accuracy can be achieved if bregma is used as the reference point for work with rostral structures and the interaural line for work with caudal structures.
References (4)
- G. Paxinos et al.
The Rat Brain in Stereotaxic Coordinates
- B.M. Slotnick et al.
Variability in the stereotaxic position of cerebral points in the albino rat
Brain Res. Bull.
(1980)
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