In celebration of SIDB’s 5th year anniversary on the 1st April 2022, during March we showcased a paper published from across SIDB every day on Twitter. For our final week we showcased two papers a day!
This study details the first cell-type-specific translation profile of Fragile X Syndrome (FX) mouse model (Fmr1-/y ) neurons. Surprisingly, it was shown that many over-translating mRNAs are protective rather than pathological. One example of this is muscarnic receptor M4, which can be positively modulated to correct aberrant plasticity and audiogenic seizures in the Fmr1-/y mouse. This shows that cell type-specific translation profiling can identify new disease mechanisms and novel therapeutic targets for FX.
The PAX6 gene is essential for normal brain development. It controls the activities of hundreds of other genes and its mutation has catastrophic effects. For example, in humans, mutations of both copies of PAX6 cause death before or shortly after birth and mutations in one copy cause eye defects, structural brain defects and intellectual disabilities. One well-documented reason these problems occur is that PAX6 is essential for normal cell proliferation in the embryonic brain. This might not be the whole story, however. PAX6 might also be important for ensuring that the neurons that are made function properly. We set out to discover whether this is the case. We found that mutating PAX6 at the time when newborn brain cells are becoming neurons altered how they developed their shapes. It also resulted in them becoming hyperactive, generating more electrical activity in response to the same amount of stimulation. Most studies on PAX6 have focussed on its actions in dividing cells. Our results revealed previously unknown roles for it in maturing neurons in the developing brain. They show how the same gene can have different functions at different stages of a cell’s development, providing interesting insights into the mechanisms of normal and abnormal brain development.
Evolutionary theory and behavioral biology suggest that kinship is an organizing principle of social behavior. The neural mechanisms that mediate kinship behavior, were not previously known. Lesion effects, developmental changes and the ordered representation of response preferences according to kinship—an organization we refer to as nepotopy—point to a key role of the lateral septum in organizing mammalian kinship behavior.
Padamsey et al. show that under food restriction, mouse visual cortical neurons save ATP by decreasing excitatory currents. Compensatory mechanisms preserve spike rate but decrease coding precision of visual information.
Supplementation with the fat mass- regulated hormone leptin restores coding precision.