In a pivotal study that enhances our knowledge of memory creation, researchers reveal that the flexibility of chromatin—DNA organized within the cell—significantly determines which neurons participate in forming particular memories.
When we create a new memory, the brain experiences both physical and functional alterations, referred to collectively as a “memory trace.” This memory trace illustrates the distinct activity patterns and structural changes in neurons that happen when a memory is established and subsequently recalled.
So, how does the brain “choose” which neurons take part in a memory trace? While previous studies pointed out that a neuron’s inherent excitability is influential, the conventional understanding of learning has largely overlooked the neuron’s nucleus, its command center. Within the nucleus lies an unexplored dimension: epigenetics.
Every living organism’s cells contain identical genetic material encoded in their DNA; however, various cell types—such as skin, kidney, or nerve cells—express distinct sets of genes. Epigenetics refers to the methods through which cells regulate gene activity without altering the DNA sequence itself.
Recently, scientists from EPFL, under the guidance of neuroscientist Johannes Gräff, have investigated whether epigenetics could impact the selection of neurons for memory formation. Their study involving mice, published in Science, indicates that a neuron’s epigenetic condition critically influences its involvement in memory encoding. “We are illuminating the initial phase of memory creation at a DNA-centered perspective,” states Gräff.
Gräff and his team explored if epigenetic variables could affect a neuron’s “mnemonic” capacities. A neuron is considered epigenetically open when the DNA in its nucleus is relaxed and unraveled, while it is closed when the DNA is tightly packed.
The researchers discovered that neurons in an open chromatin state were more likely to join the “memory trace,” representing the limited group of neurons that exhibit electrical activity during new learning experiences. In fact, those neurons with an open chromatin configuration also demonstrated increased electrical activity.
The EPFL team then utilized a virus to introduce epigenetic enzymes to artificially create an open state in the neurons. They observed that the mice subjected to this underwent enhanced learning abilities. Conversely, employing a method to compact the neurons’ DNA eliminated the mice’s learning capacity.
The results pave the way for new insights into learning processes that account for changes within the neuron’s nucleus and could ultimately lead to treatments aimed at enhancing learning. Gräff elaborates: “This research shifts the prevailing neuroscientific perspective on learning and memory, which has primarily emphasized synaptic plasticity, to underscore the significance of events occurring within a neuron’s nucleus and its DNA. This is particularly vital, considering that numerous cognitive disorders, including Alzheimer’s disease and post-traumatic stress disorder, are associated with malfunctioning epigenetic mechanisms.”
