Giraffes’ long necks are perfectly suited to harvesting tender leaves beyond the reach of other herbivores. Pondering the genesis of this phenomenon, two giants of modern biology, Jean-Baptiste Lamarck and Charles Darwin, arrived at remarkably different hypotheses. Lamarck believed that constant stretching of the neck somehow stimulated its growth. The giraffe would then pass along this new trait to its offspring. In effect, this newer, longer neck was a direct result of a giraffe’s interaction with its environment. By contrast, Darwin’s theory posited that traits evolve as part of a random, gradual process. The giraffes that happened to have been born with longer necks thanks to a random genetic mutation were better fed and thus healthier than their shorter-necked counterparts, making them more likely to live long enough to breed and pass on this trait. Because this mutation conferred a specific advantage to long-necked giraffes that aided their survival, the trait was preserved in future generations.
Lamarckian theories about the influence of the environment were largely abandoned after scientists discovered that heritable traits are carried on the genes encoded by our DNA. A recent study, however, published by neuroscientists Junko A. Arai, Shaomin Li and colleagues at Tufts University, shows that not only does the environment an animal is reared in have marked effects on its ability to learn and remember, but also that these effects are inherited. The study suggests that we are not the mere sum of our genes: what we do can make a difference.
The neurobiological investigation of environmental effects on learning and memory began in the late Sixties and early Seventies, when Mark Rosenzweig and colleagues examined how manipulating levels of sensory stimulation, exercise and social interaction affected rats’ behavior. Laboratory rats typically live in a cage with bedding, food and water but little else. In the enriched environments (EE) that Rosenzweig’s group created, animals got access to a changing roster of toys, and increased opportunities for socialization and exercise. The brains of EE rats were larger and they outperformed controls (which were housed in typical cages) in learning and memory tasks. Subsequent work by researchers looking at the cellular level has shown that EE triggers changes in neural morphology (shape), resistance to neurodegenerative disease and learning-related neural activity.
Recently, Arai, Li and colleagues extended this line of inquiry, examining the role that EE plays in long-term potentiation (LTP), a form of synaptic strengthening that supports learning and memory. The physiological signature of LTP is an increase in the baseline level of a neuron’s electrical activity. Arai and Li showed that LTP in the hippocampus, a key brain structure involved in learning and memory processes, is greater in mice reared in EE.
What’s more surprising, however, is that EE is also sufficient to “rescue” a memory defect present in genetically altered mice. Parent mice born with the defect that were then exposed to EE as juveniles did not pass the same memory defects to their offspring. Their enriched surroundings corrected their genetic deficit.
How does this correction occur? Specific molecular pathways are required to generate LTP. When scientists silence the parts of the DNA code involved in the function of one of these pathways using what geneticists call “knock out” technology, as was the case in the mutant mice with a memory defect, both LTP and memory functioning are impaired. Arai and Li showed that EE increased LTP volume in wild-type (non-mutant) mice. Interestingly, mice that have had a standard molecular pathway required to induce LTP knocked out can still induce LTP. The researchers found that this EE-related LTP is induced via a novel molecular pathway that arises as a direct result of EE exposure. Moreover, they found that the enhanced LTP capacity of wild-type mice, and the rescued capacity for LTP in knock-out mice, can be transmitted epigenetically (that is, without any changes in their genetic code) from mother to offspring. Surprisingly, this transmission was true even when their offspring were raised in a conventional environment.
Is It Really the Environment?
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.
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