Interview with Tomás J Ryan - Debunking Amnesia

What is learning and memory? Is amnesia really a loss of stored memories or something more? Find out below.

Contents

  1. Basics
  2. Video
  3. Quick Breakdown
  4. Optogenetics
  5. Memory Engram Cells
  6. More Research - Tomás J Ryan's Studies

Basics

Recent studies have shown that spatial memories are encoded as sparse populations of cells that are activated during learning and are necessary for the retrieval of specific memories.

We refer to these cells as "memory engram cells" and the focus of Tomás J Ryan and his team is to understand how engram cells are able to store specific memories as information. 

Read more about Tomás J Ryan here.

Video

Quick Breakdown

Here is a quick summary/breakdown of the video above.

  • The old storage theory of amnesia is WRONG.
    • The problem is the ability to retrieve the memory.
    • Short term memory lasts a few hours. It is very disruptable (long term is not).
    • Long term memory lasts your entire lifetime. It requires transcription and translation of many different genes. 
  • We have many different genes that regulate memory.
    • They are different for short term and long term - playing roles at different stages.
    • Most popular was CREB (turns on other genes).
    • Engrams cells are structures in the brain where memories are stored. R
    • They used optigenetics to prove engram cells were important for memory.
    • Engram cells only account for 4-6% of the brain cells in the hippocampus (of mice). V
  • Consolidation idea - a short term memory (unstable) forms into a long term memory (stable), thus stabilizing the engram.
  • Optogenetics - let's us express photoactivatable opsins in whatever region of the brain we want. 
    • The brain is electrically active.
    • They put certain opsins into brain cells and then stimulate them with light.
    • These opsins can conduct ions - putting positively charged cations from the external environment of the cell into the neuron. 
    • This depolarizes the cell, which results in an action potential (creating neuronal activity).
  • What they did at MIT was integrate optogenetics and memory engram cells. 
    • They tested parts of the brain using a transgenetics - they took immediate/early genes (genes that show activity as a function of neuronal spike) and used opsins to only activate those genes. 
  • Amnesia and Memory
    • Learning is the enhancement of synaptic connections.
    • Memory is a stable thing in the brain and can last for your entire life. 
    • Learning and recall are not "things", they are activities. 
    • Learning = process of making a memory. Recall = process of retrieving a memory. 
    • So the problem is not memory itself. 
    • Amnesic engram cells have a loss of synaptic strength
    • Increasing the synaptic strength helps get the memory (which is commonly seen in Alzheimer's (AD), Huntington's (HD)). 
    • If you increase the synaptic potentiation (increasing the dendritic spine density), esp. of the amnesic engram cells, you can get natural access to those memories.
    • Neurotrophic factors (BDNF, NGF, CNTF, GDNF) do this, but are not localized nor memory specific.
    • Learning something new (about something you are amnesic about) will train your brain to those particular engram cells.
    • Once you activate the engram cells (with optogenetics), you can restore access to old information and add new information on those amnesic memories. 
    • Without dealing with the cause, you probably won't be able to really restore memories (in diseases like AD, HD, etc.)
    • In late stages of neurodegeneration, you may actually lose memories.
  • Actions to take for prevention
    • Stay mentally active
    • Engage in physical exercise
  • Actions to take for amnesia (acute memory loss)
    • Do everything to remind yourself of those experiences
    • Retrain on the "forgotten" pieces
  • We briefly discussed gene expression and histone acetylation to enhance memory.

Optogenetics

 
http://www.cell.com/neuron/fulltext/S0896-6273(15)00677-7

http://www.cell.com/neuron/fulltext/S0896-6273(15)00677-7

 

There are 4 ways to examine neural mechanisms of encoding memory in mice:

  1. Transgene expression - Genes that are artificially introduced into or deleted from (brain) cells. R
  2. Activity-dependent expression - limit the expression of the transgene, such as using immediate early genes (IEGs), which naturally turn on immediately after neuronal activity. It shows shich neurons are being fired in the cells. R
  3. Time-dependent expression - limiting the expression of the transgene within a specific time window. R
  4. Non-electrical control of neural firing - activate neurons with light (optogenetics). Ion channels control neuronal firing. Ion gates admit charged molecules (mostly sodium, potassium, and chloride) under the direction of certain amino acids and their derivatives (usually glutamate or GABA) acting on synaptic receptors. R

Memory Engram Cells

The term engram was first invented as "the enduring though primarily latent modification in the irritable substance produced by a stimulus (from an experience)". R

Interaction with the world leaves a physical residue within the excitable substance of the nervous system. R

Some internal modifications may manifest directly as a behavioral change or memory; others may be accumulated over time into a learned behavior. R

Increasing synaptic strength is important for memories because the brain may adaptively modulate the accessibility of stored information by altering the strength of transmission at synapses. R

Permanently enhanced synaptic transmission does not and cannot store the memory information itself. R

Synaptic strength delegates engram retrieval.  R

 
http://www.cell.com/neuron/fulltext/S0896-6273(15)00677-7

http://www.cell.com/neuron/fulltext/S0896-6273(15)00677-7

 

By activating certain engrams with optogenetics, you can recall specific memories. V

If you want to see how a memory can turn into an instinct, watch the last part of this video.

More Research - Tomás J Ryan's Studies