To ensure that the enhanced LTP seen in the offspring was due to the mother’s exposure to EE as a juvenile, the authors carried out several clever controls. To eliminate the possibility that enhanced LTP may be paternally mediated, female wild-type and knock-out EE mice were mated with conventionally raised males. The researchers found that offspring of the wild-type mice had greater LTP capacity and that LTP was restored to baseline levels in the knock-outs’ offspring. To demonstrate that effects occur in utero, offspring of EE mice were raised in standard laboratory housing by conventionally raised mothers. As expected, LTP was enhanced in offspring of wild-type mice, and restored to baseline levels in knock-out mice.
Next, the authors compared the memory functioning of wild-type and LTP knock-out mice, to gauge how EE affects mice at the behavioral level. They assessed contextual memory using what is called the contextual fear-conditioning paradigm. Mice placed in a wire cage are given a mild shock; typically, mice respond to threats by freezing. To assess whether the mouse learns to associate the cage where shocks are administered with the shock, researchers measure the overall freezing time of the mouse during initial conditioning (training). Later, they test memory for this association by observing freezing upon re-exposure to the cage, either hours or days later, in the absence of shock. The researchers found that, while both wild-type and knock-out mice expressed similar levels of freezing during conditioning, memory for the context where the shock occurred was impaired in the knock-outs. Here’s where it gets interesting: offspring of knock-out mice exposed to EE as juveniles spent just as much time frozen as their normal counterparts. This finding provides a crucial link between EE exposure, LTP and the novel EE-induced molecular pathway supporting LTP and behavior.
The Importance of Context
Studies such as this one, investigating how the environment influences the epigenetic propagation of heritable traits, are a hot area of research. The topic’s appeal lies in the scientific credence it lends to the notion that we and our offspring are not simply at the mercy of a random evolutionary process and inherited genetic script but are, if not masters of our own fate, at least capable of influencing its course. On a practical level, such findings suggest that novel therapies based on simple interventions such as EE could mitigate the effects of genetically inherited diseases.
Although these implications are seductive, these specific results usually aren’t easily generalized, or broadly applied, to human populations, however. EE seemed to rescue the memory impaired phenotype of the non-enriched knock-outs, but it bears reiterating that under this manipulation, the wild-type mice that demonstrated improved contextual memory following fear-conditioning did not demonstrate enhanced LTP.
What is true for highly derived lines of conventionally housed (read: sensory deprived) laboratory mice may not generalize to non-deprived humans. We should not assume that children born to mothers who were chronically bored during their adolescence will have memory deficits. Second, in order to generate conclusions, scientists must control the number of variables in the experiment. In these experiments, scientists only analyzed one type of learning under a very specific set of parameters. It is entirely possible that these same knock-out mice raised in the enriched environment would be unable to learn if the stimulus—the context association tested—was for an emotionally positive, rather than a negative, event. On a related note, there are many ways to induce LTP. Thus, it’s at least possible that the molecular pathways explored by Arai, Li and colleagues might mediate LTP specific to contextual memory formation following fear conditioning.
Despite these caveats, this study provides some posthumous vindication of Lamarck’s theories of change and inheritance. Although Darwin’s theory of evolution and natural selection is still dogma, modern science is hinting that there is nevertheless a place for some of Lamarck’s intuitions in a complete account of the mechanisms of inheritance.