Building Blocks of Memory in the Brain

Summary

This video script delves into the concept of engrams, the physical substrates of memory in the brain. It explores how memories are encoded as changes in neuron connections, with engram sparsity maintained through competition among neurons. The script discusses fear-conditioning experiments to study memory formation and the role of immediate-early genes in marking memory-encoding neurons. It also touches on how engrams are distributed across the brain and how memories can be linked through shared neurons, influencing memory recall and abstraction.

Takeaways

• 🧠 The concept of an engram, introduced by Richard Semon, refers to the physical changes in the brain that are a result of learning or experience.
• 🔬 Memory storage is believed to be a result of changes in the patterns of neural communication.
• 🐀 The fear-conditioning paradigm is a popular method used to study memory formation in model organisms like rodents.
• 🌟 Immediate-early genes like fos and Arc are activated during learning and can be used as markers for memory encoding.
• 🔦 A technique involving a harmless virus can be used to make neurons glow, allowing for the visualization of memory-encoding neurons.
• 💊 The timing of memory tagging can be controlled with drugs to ensure that only neurons involved in specific memories are tagged.
• 🔄 The activation of engram neurons is both necessary and sufficient for memory recall.
• 🧬 Engrams are sparse and their size is conserved across different memories, suggesting an internal mechanism for memory allocation.
• 🏎 Neurons with higher intrinsic excitability are more likely to be recruited into a memory trace.
• 🌐 Engrams for a single memory can be distributed across various brain regions, forming what is known as an engram complex.
• 🔗 Memories can be linked by sharing neurons, which can occur during initial memory allocation or through core retrieval.

Q & A

What is the concept of an engram?

An engram is considered a fundamental unit of physical memory substrate, referring to the lasting physical changes in the brain that occur after learning or experiencing something.

Who coined the term 'engram' and when?

The term 'engram' was coined by German biologist Richard Semon in the early 20th century.

How does memory recall relate to engrams according to Semon's theory?

According to Semon, once an engram is formed, it becomes dormant and can be awakened by similar experiences or parts of the original event, which is what we experience as memory recall.

What is the role of neurons in memory storage?

Memories are believed to be stored as changes in patterns of how neurons communicate with each other, through the generation of electrical pulses encoding incoming stimuli.

What is a fear-conditioning paradigm and how is it used to study memory?

A fear-conditioning paradigm is an experimental setup where memory is defined as forming an association between a neutral stimulus and an aversive stimulus. It's used to study memory formation by observing the subject's response to the previously neutral stimulus after conditioning.

What are immediate-early genes and their significance in memory studies?

Immediate-early genes are a special class of genes that rapidly and selectively get activated in neurons undergoing plastic changes during learning. They are considered markers for memory encoding.

How can the activation of immediate-early genes be visually observed in neurons?

The activation of immediate-early genes can be visually observed by linking their activation to a reporter process such as a fluorescent protein. This is achieved by using a harmless virus to genetically modify neurons to express the fluorescent protein under the control of the same promoter region as the immediate-early genes.

What is the problem with observing engram neurons immediately after fear conditioning?

The problem is that it's impossible to carry out fear conditioning right after the surgery because the animals need to recover, and the virus needs time to spread. This means the animal may have already formed other memories, making it difficult to identify which neurons correspond to the associative memory of interest.

How can the timing of memory tagging be controlled experimentally?

The timing of memory tagging can be controlled by engineering the genetic machinery to lie dormant and activate only upon the presence or absence of a certain chemical compound, allowing for transient activation during the experiment.

What does it mean for the activation of engram neurons to be both necessary and sufficient for memory recall?

It means that not only is the activation of these specific neurons required for the memory to be recalled, but also that activating these neurons alone, even in the absence of the usual conditional stimulus, can induce the memory recall.

How do engrams form and what determines which neurons become part of an engram?

Engrams form as a result of experiences activating a large number of neurons, but only a small proportion of these active neurons become part of the engram. The selection process is not fully understood, but it is known that neurons with elevated excitability have a higher probability of being recruited into a memory trace.

What is the significance of engram sparsity and how is it maintained?

Engram sparsity refers to the fact that only a small number of neurons are allocated to storing each memory, which is thought to be optimal for storage capacity and robustness to noise. This sparsity is maintained through competition, where the most excitable cells are chosen for the memory trace.

How do different brain regions contribute to the formation of a single memory?

Different brain regions contribute to a single memory by encoding specific aspects of the full memory. For example, the amygdala might hold emotional valence, the hippocampus handles spatial context, and the cortex encodes sensory experience.

How can memories be linked in the brain?

Memories can be linked by encoding the connection between them as the degree of overlap between the populations of engram neurons. This overlap can occur during initial memory allocation or through core retrieval where initially non-overlapping engrams become reactivated together.