By: Gregory Brown, MD/PhD Candidate
Have you ever considered what a memory actually is? The brain is a physical organ, so a memory must be some combination of cells functioning together to remember that time you sat on a beach in south France with a bottle of wine and the wind blowing through your hair. The engram, is term used to for neurons underlying and encoded memory.
The engram describes the physical trace of a memory in the brain. The idea is that some physical substrate must encode the abstract concept of a memory.
The engram: a physical memory trace
The engram has been largely elusive due to the sparse encoding of the memories throughout the brain. When people have a stroke or brain damage, they may lose some memories, or lose them temporarily. Localizing memory to a specific set of neurons is quite challenging.
There has also been a lack of techniques to study the engram with sufficient spatial and temporal resolution. The brain changes so rapidly. Models predicting even 3 neuron circuits become unmanageable after a few seconds. The brain is (spoiler) complex.
The process of the engram involves encoding and consolidation of a stimulus. A cycle then ensues, the engram, and subsequently the perception of the memory, is retrieved or reactivated followed by reconsolidation and re-retrieval. This largely explains why your ability to remember material for tests improves the more times you review the material.
The engram involves four key components:
- Engram neurons are active at the time of learning.
- These same neurons are then also active during the retrieval process.
- Ablation or inactivation of these neurons prevents retrieval, which may indicate loss of the memory
- Stimulation of these neurons are sufficient to induce memory recovery. These four attributes are indicative of engram neurons.
Stimulation of neurons activated at memory encoding can induce memory retrieval
The fourth attribute: activation of certain neurons induces memory retrieval, is the focus of a study by Liu et al. They hypothesize that stimulation of neurons activated during a fearful event is sufficient to induce a memory of fear.
The work builds upon the three other components of the engram in an attempt to understand the formation and storage of a memory in the brain. The authors focus on fear memories, since these are strongly encoded.
The scientists used a scientific technique that is gaining prominence: optogenetics. Optogenetics provides the ability to selectively activate genetically engineered neurons. The basic principle uses the gene that is responsible for light activation of cells in the eye (rhodopsin) to selectively activate brain cells.
The authors induced a fearful memory by pairing a tone with a shock. Therefore, the memory of the tone became associated with the fear of a shock. This is a type of conditional memory.
The authors investigated the effects of neuronal stimulation on memory retrieval. By selectively activating specific brain cells with light, the mice displayed a fear response, indicating they were remembering the fearful event.
To ensure this was truly a memory response. The authors played the tone without the shock. And activation of these neurons did not result in a fear response.
This suggests a specific set of neurons, the engram, are involved in a specific memory encoding and retrieval.
Overall, these findings are supportive that a specific combination of neurons that are active at time of encoding can be stimulated to induce a behavioral response similar to that expected from memory retrieval, which correspond to components one and four of the engram.
Imagine if you could force people to recall memories by activating certain neurons. Or you could plant false memories. These are the boundaries of the science of memory.