Johenning, F. | Search bioRxiv

bioRxiv2025

Epigenetic inheritance of complex learning abilities in the mammalian brain

For several decades, the question of whether cognitive and learning capacities can be inherited through non-genetic mechanisms has been the subject of ongoing debate. Here, we provide the first evidence of transgenerational inheritance of enhanced ability to learn complex tasks in the mammalian rodent brain. These inherited learning enhancements are not limited to specific stimuli, sensory modalities, or learning paradigms. Using behavioral, cellular biophysical, methylomics, genetics and molecular methods, we find that the inherited epigenetic modifications reflect an enhanced neuronal learning state, driven by increased intrinsic neuronal excitability in most pyramidal neurons in the relevant neuronal networks. This enhancement is mediated by persistent downregulation of the muscarinic M-current and is associated with widespread changes in DNA methylation, notably within coding genes associated with the M-current, the Kv7 pathway, in the hippocampi of trained F0 rats, as well as in non-coding RNAs in their sperm samples. Remarkably, a significant portion of these DNA methylation changes were also observed in the hippocampi of their untrained F1 offspring. These findings suggest that complex learning abilities can be inherited in the mammalian brain, as the offspring of trained rodents are born with the biophysical modifications that enable them to become super-learners, the exact change that occurs in their parents brains only after the rule learning.

neuroscience↗

bioRxiv2019

Circuit-specific dendritic development in the piriform cortex

Dendritic geometry is largely determined during postnatal development and has a substantial impact on neural function. In sensory processing, postnatal development of the dendritic tree is affected by two dominant circuit motifs, ascending sensory feedforward inputs and descending and local recurrent connections. In the three-layered anterior piriform cortex, neurons in the sublayers 2a and 2b display vertical segregation of these two circuit motifs. Here, we combined electrophysiology, detailed morphometry and Ca2+ imaging in acute mouse brain slices and modeling to study circuit specific aspects of dendritic development. We observed that determination of branching complexity, dendritic length increases and pruning occurred in distinct developmental phases. Layer 2a and layer 2b neurons displayed developmental phase specific differences between their apical and basal dendritic trees related to differences in circuit incorporation. We further identified functional candidate mechanisms for circuit-specific differences in postnatal dendritic growth in sublayers 2a and 2b at the meso- and microscale level. Already in the first postnatal week, functional connectivity of layer 2a and layer 2b neurons during early spontaneous network activity scales with differences in basal dendritic growth. During the early critical period of sensory plasticity in the piriform cortex, our data is consistent with a model that proposes a role for dendritic NMDA-spikes in selecting branches for survival during developmental pruning in apical dendrites. The different stages of the morphological and functional developmental pattern differences between layer 2a and layer 2b neurons demonstrate the complex interplay between dendritic development and circuit specificity. Significance StatementSensory cortices are composed of ascending sensory circuits that relay sensory information from the periphery and recurrent intracortical circuits. Dendritic trees of neurons are shaped during development and determine which circuits contribute to the neuronal input space. To date, circuit-specific aspects of dendritic development and the underlying mechanisms are poorly understood. Here, we investigate dendritic development in layer 2 of the piriform cortex, a three-layered palaeocortex that displays a clear vertical segregation of sensory and recurrent circuits. Our results suggest that dendritic development occurs in distinct developmental phases with different circuit-specific properties. We further identify candidate mechanisms for neuronal activity patterns that could determine differences in circuit-specific dendritic development.

neuroscience↗