Learning & Memory Part 2: Neuronal Encoding and Memory Stability

Learning and Memory Part 2: Neuronal Encoding, Memory Stability, False Memories

Learning Objectives

  • Be able to:

    • Describe the process of cellular consolidation.

    • Compare the similarities between short-term and long-term memory phases with the early and late phases of Long-Term Potentiation (LTP).

    • Explain what place cells are and how they contribute to episodic memory.

    • Identify the neuronal correlate of working memory observed in the dorsolateral prefrontal cortex (dlPFC) of primates and provide an example of how working memory can be assessed.

    • Define re-consolidation.

    • Describe the false memory experiment and explain what this tells us about the neural basis of memory.

Synaptic Plasticity and Memory Hypothesis

  • Memory Systems:

    • Long-term Memory:

    • Declarative (Explicit):

      • Episodic: Memory of personal experiences.

      • Semantic: General knowledge.

    • Nondeclarative (Implicit):

      • Skill Learning (Procedural): Performing tasks without conscious awareness.

      • Priming: Exposure influences response to a stimulus.

      • Classical Conditioning: Associating a neutral stimulus with an unconditioned stimulus.

      • Nonassociative Learning: Changes in response to a single stimulus over time.

      • Spatial Learning Memory: Navigational abilities.

Brain Regions Involved in Memory

  • Hippocampus: Associated with declarative memory and relational learning.

  • Medial Temporal Lobe: Plays a role in memory formation.

  • Neocortex: Involved in long-term memory storage.

  • Prefrontal Cortex: Maintains information in working memory.

  • Striatum, Motor Cortex, cerebellum: Involved in procedural memory.

Neural Changes in Associative Learning

  • Appetitive Conditioning: Involves mesolimbic/mesocortical pathways.

  • Fear Conditioning: Involves defensive circuits.

  • Declarative Memory Systems:

    • Importance of Hippocampus shown in patient H.M., emphasizing its role in memory and synaptic plasticity through LTP.

Hippocampal Place Cells

  • Place Cells: Neurons in the hippocampus that fire in specific locations. They help create a cognitive map of the environment by encoding spatial locations.

    • Example: A neuron that fires consistently in a particular area but not elsewhere; collectively, they represent the explored environment.

Cognitive Maps and Spatial Memory

  • Stability of Maps: Depends on synaptic plasticity, such as LTP.

    • Wild-type mice exhibit stable place cell mapping, while mutant mice lacking calcium/calmodulin-dependent protein kinase II (CaMKII) show inconsistent mappings.

  • Entorhinal Cortex: Houses grid cells that fire in a grid-like pattern, contributing to spatial orientation in three dimensions.

Working Memory

  • Definition: The ability to hold information temporarily for the purpose of using it to guide behavior, without external input.

  • Prefrontal Cortex (PFC): Critical for maintaining information in working memory.

  • Neuronal Activity: Persistent firing observed in the dlPFC during tasks requiring memory.

Testing Working Memory

  • Tested using the Delayed Non-Match to Sample Task.

    • Example: After presenting an image and removing it, a delay occurs during which memory is needed before the subject makes a choice based on their memory of the image.

Dorsolateral Prefrontal Cortex (dlPFC)

  • Critical for working memory, characterized by:

    • Single-cell persistent firing.

    • Recurrent activation among local cells and long-range connections.

Memory Consolidation and Reconsolidation

  • Non-consolidated Memories: Not all memories persist after a day.

  • Electroconvulsive Shock (ECS): Can produce retrograde amnesia by disrupting memory consolidation processes.

  • Anisomycin: An antibiotic that interferes with protein synthesis and prevents memory formation. It is used to demonstrate the difference between short-term and long-term memories:

    • Short-term memory (STM): Lasts seconds to hours, sensitive to disruption, does not require new protein synthesis.

    • Long-term memory (LTM): Lasts days to a lifetime, resistant to disruption, requires new protein synthesis.

Memory Reconsolidation

  • When memories are retrieved, they become labile and can be updated or disrupted.

  • False Memories: Memories for events that did not happen, often include misinformation. They occur when retrieval of one memory triggers another, leading to confusion over the source of the information.

    • Example: 75% of false convictions rely on eyewitness testimony.

Implanting False Memories in Mice

  • Dr. Tonegawa's lab utilized genetic and optogenetic methods to induce false memories in mice.

    • The process involves:

    1. Tagging Neurons in a neutral environment (e.g., a red room) to identify neurons activated during exploration using a special marker based on c-Fos protein expression.

    2. Activating Tagged Neurons in a different context (e.g., grey room) while administering shocks to create an association between places and fear.

    3. Testing Fear Memory: Mice show fear responses to contexts they were never shocked in if neural activation occurred during the prior fear conditioning process, demonstrating false memory formation through neural circuits.

Memory as a Reconstructive Process

  • Encoding involves various sensory attributes before consolidation, while retrieval can fail at any stage leading to forgetting. Memory retrieval involves reconstructing previously stored information from long-term memory.