Untitled Quiz

LTP and Learning

• LTP experiments are artificial, inducing changes via low-intensity, high-frequency electrical events bypassing sensory input.
• Hippocampal slices model the brain, but are one step removed from the actual brain.
• Long-term changes at individual synapses, associated with LTP, don't fully represent memory.
• Memories are produced by organisms interacting with their environment.
• Observing behavior to understand learning and memory requires training and testing.
• Behavioral changes are influenced by more than just learning and memory—many processes impact behavior.
• Experimental methods must account for other factors influencing behavior changes.

Memory Processes

• Memory traces (engrams) represent the physical basis of memory.
• Mouse models are used to train mice to navigate mazes, assess post-training time to complete the task, lesion a brain area, then test.

Types of Memory

• Short-term memory (STM) rapidly decays, while long-term memory (LTM) decays more slowly and is inactive.
• STM traces are active; LTM traces are inactive.
• Memory traces can transition from active to inactive states.

Memory Consolidation

• Memory consolidation is the process of stabilizing memory traces, making them resistant to disruption.
• Key factors, possibly, are CREB phosphorylation, protein degradation, and mTOR activation
• Three main principles are needed: Translation and transcription of the initial behavioral experience
• Consolidation processes can continue for at least 24 hours; this is regulated by autoregulatory positive feedback loops.
• Variables of memory, that can be manipulated
• Pharmacological or genetic manipulation can influence molecules considered to be important to memory.
• The retention interval is the time between training and testing.

Memory Tasks

• Recognition memory tasks test for recognition of novel objects. Rats typically spend more time exploring a novel object.
• Inhibitory avoidance task. Procedure: rodents are stimulated. Expected results: increased latency (a longer time taken) to cross to the other side of the box if they had learned.
• Fear conditioning. Procedure: rodents in a box are stimulated with a tone or a shock. Expected results): increased freezing behavior with a shock. Thus, more freezing behavior demonstrated the strengthening of the memory trace.
• Water escape task. Procedure: rats placed in a pool of water. Rats need to locate a hidden platform. Expected results: Decreased latency(faster time) if they had learned..

Transgenic Mice

• Transgenic mice are modified to have a specific gene for Cre recombinase attached to the promoter region. Other genes with interest are surrounded by loxP sites, the Cre recombinase interacts with loxP sites and cuts out the target gene.
• A full knockout is where a specific gene has been removed entirely.
• Conditional knockdown is where a specific gene is removed in specific cells or at specific times in the animal.

Optogenetics

• Optogenetics uses light to control neurons with high temporal precision.
• Opsins (proteins) respond to light. Channels (e.g. channelrhodopsin, halorhodopsin) change the ion permeability, activating or inhibiting neurons
• Genetic engineering creates designer receptors (DREADDs) activated only by particular synthetic drugs.
• Viral vectors allow delivery of these receptors into specific neurons

Neurotransmitters and Memory Formation

• Sensory input creates connections between neurons; the strength of these connections changes from experience.
• Cell assemblies (neurons) that fire together wire together. This is the basis of memory.
• Multiple neurotransmitters are involved (e.g., glutamate binding to AMPA and NMDA receptors).

NMDARs and Memory

• Functional NMDA receptors have GluN1, GluN2A, and GluN2B subunits—all functional receptors have GluN1, and some have GluN2A and/or GluN2B subunits.
• NMDARs are necessary for generating LTP, a mechanism believed to be necessary for some forms of memory.

Consolidation Principles - Time-Dependence

• Consolidation is a process that stabilizes memories, making them resistant to disruption.
• Short-term memories may not require new protein synthesis.
• Long-term memories usually depend on new protein synthesis (in multiple waves).
• Consolidation involves both local protein synthesis and genomic signaling (transcription and translation).
• This includes the BDNF-TrkB-mTOR pathway for the first wave of protein synthesis , allowing for memory retention for 2 days and C/EBP for the second, lasting up to 7 days

Epinephrine and Memory

• Epinephrine can modulate memory by influencing glucose release from the liver.
• Adrenergic receptors (ARs) on the liver mediate this effect.
• Arousal increases epinephrine release, which can enhance memory consolidation by providing energy for protein synthesis.
• Age-related memory declines might be linked to reduced liver responsiveness to epinephrine, leading to lower glucose availability to support brain function.

Freezing Response in Arousal and Memory

• The freezing response, which represents an animal's innate reaction to a perceived threat or danger, can be connected to memory modulation.
• Pharmacological blockade of the CaMKII pathway can inhibit memory acquisition in both contextual and auditory-cued fear conditioning.
• Factors like the retention interval (time between training and testing) affect memory consolidation. Short-term memories might only persist a few hours, while long-term memories last for days or weeks.

Other Key Concepts

• Memory for a taste aversion is mediated by the insular cortex.
• Injecting ZIP into the insular cortex can erase taste aversion memory.
• PKM-zeta can prevent endocytosis of AMPA receptors, thereby preserving memories.
• Blocking NMDA receptors can affect memory consolidation and/or retrieval depending on the timing of the block.