A biophysical mechanism for epigenetic inheritance of enhanced complex learning capabilities

Acquisition of the ability to learn complex tasks, termed `rule learning`, is mediated by enhanced intrinsic neuronal excitability throughout the neuronal population in the relevant brain areas, which results from decreased conductance of slow potassium current(s).

Here we show that rats trained in complex tasks pass on trans-generationally superb learning capabilities. Such inheritance is also evident when only one of the parents (male or female) is trained, if the F1 generation is fostered by non-trained females and if the F2 or F3 generation is trained without any training of the F1 generation. Notably, offspring excel also in other, completely novel tasks.

At the cellular level, the biophysical properties of CA1 pyramidal neurons of trained rats’ offspring differ significantly from neurons of controls’ offspring. Their excitability is higher, as result of reduction in the M-current mediated slow potassium current(s), the very same change induced in the brains of the F0 rats only after they acquire the rule.

Thus, offspring excel in complex learning tasks since they are born with neurons that show the same biophysical change induced in parents` brains by training for rule learning.

Analysis of mRNA expression levels show that the hippocampi of trained offspring differs from the controls` offspring hippocampi in more than 500 genes. In particular, we found downregulation of genes that code for channels that suppress intrinsic excitability, and of genes that code for synaptic receptors.

We suggest that these changes create favourable set point for future increased plasticity, thereby granting trained rats` offspring superb learning capabilities.