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PSYC 3832 NEURAL BASIS OF LEARNING Week 11 Chapter 14 TIAN YU, PhD Department of Psychology College of Liberal Arts and Sciences Chapter Goals Under some conditions, retrieving or reactivating a consolidated memory can return it to an active, labile state. The goal of this chapter is to provide an understanding of the empirical facts and theoretical concepts that are associated with this observation. This will be done by discussing: • Key empirical findings • Active trace theory • Reconsolidation theory • How retrieval returns the trace to an unstable, labile state • How the trace is restabilized • The concept of trace updating Reactivated Memory Disrupted by ECS (A) A fear-conditioning experiment was used to study the vulnerability of a reactivated memory—a noise CS was paired with a shock US. In one condition, 24 hours after fear conditioning, the CS was presented to reactivate the fear memory. Some animals received electroconvulsive shock (ECS), while others did not. In the second condition, the fear memory was not reactivated, but animals received either ECS or no ECS. All animals were tested for fear of the CS. (B) The results of the experiment. Note that when the memory trace was reactivated by briefly presenting the CS, ECS disrupted the memory for the CS–shock experience. ECS had no effect when it was presented in the absence of shock. Active Trace Theory This figure illustrates the assumptions of active trace theory. Memories exist in either a short-term memory (STM) active state or a long-term memory (LTM) inactive state. (A) Novel experience can create an active STM trace that will decay into the inactive LTM state. (B) Retrieval cues can retrieve an inactive LTM trace and place it in the active state that then will decay into the inactive LTM state. Memories in the active state are more vulnerable to disruption than memories in the inactive state. Reconsolidation Theory: Nader’s Finding (A) The design of Nader et al.’s 2000 experiment. Rats were conditioned to an auditory-cue–CS paired with a shock–US. Following the reactivation of the fear memory, the protein synthesis inhibitor anisomycin or the vehicle solution in which the drug was suspended was injected into the lateral nucleus of the amygdala. Rats were then given either a short-term memory (STM) test or a long-term memory (LTM) test. (B) Anisomycin disrupted the long-term retention of the reactivated fear memory but had no effect on the short-term retention of the memory. (After Nader et al., 2000.) Reconsolidation Theory (A) A retrieval cue activates a well consolidated but inactive memory trace from long-term memory. The synaptic connections linking the neurons involved in the trace become unbound. However, retrieval also initiates protein synthesis and the memory trace is reconsolidated. Thus, when it returns to the inactive state it will be stable. (B) If protein synthesis is prevented, the memory trace will be weakened or lost when it returns to the inactive state. Assessing Reconsolidation Theory: Only the Reactivated Trace Needs to Be Reconsolidated Rats acquired two fear memories. However, only the reactivated memory (CS1) was disrupted by U0126, a drug that interferes with reconsolidation. How Does Reactivation Destabilize the Trace? A Role for the UPS This figure illustrates key events that destabilize the synaptic basis of a memory trace. Proteasomes Degrade Proteins Tagged with Ubiquitin Proteins PSD Ubiquitin Proteasome Proteasomes Degrade Scaffolding Protein Tagged with Ubiquitin Glutamate Calcium NMDA AMPA Scaffolding proteins Ubiquitin PSD Proteasome The collapse of the scaffold results in AMPA receptor loss from the spine.