Cellular theories of memory consolidation posit that new memories require new protein synthesis in order to be stored. Systems consolidation theories posit that the hippocampus has a time-limited role in memory storage, after which the memory is independent of the hippocampus. Here, we show that intra-hippocampal infusions of the protein synthesis inhibitor anisomycin caused amnesia for a consolidated hippocampal-dependent contextual fear memory, but only if the memory was reactivated prior to infusion. The effect occurred even if reactivation was delayed for 45 days after training, a time when contextual memory is independent of the hippocampus. Indeed, reactivation of a hippocampus-independent memory caused the trace to again become hippocampus dependent, but only for 2 days rather than for weeks. Thus, hippocampal memories can undergo reconsolidation at both the cellular and systems levels.

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Memory consolidation refers to a process by which newly learned information is made resistant to disruption. Traditionally, consolidation has been viewed as an event that occurs once in the life of a memory. However, considerable evidence now indicates that consolidated memories, when reactivated through retrieval, become labile (susceptible to disruption) again and undergo reconsolidation. Because memories are often interrelated in complex associative networks rather than stored in isolation, a key question is whether reactivation of one memory makes associated memories labile in a way that requires reconsolidation. We tested this in rats by creating interlinked associative memories using a second-order fear-conditioning task. We found that directly reactivated memories become labile, but indirectly reactivated (i.e., associated) memories do not. This suggests that memory reactivation produces content-limited rather than wholesale changes in a memory and its associations and explains why each time a memory is retrieved and updated, the entire associative structure of the memory is not grossly altered.consolidation ͉ fear ͉ memory ͉ associative learning C onsolidation is the process through which temporary or short-term memory (STM) is converted into persistent or long-term memory (LTM) (1). Much research suggests that consolidation depends on protein synthesis (2-4). Traditionally, protein synthesis-dependent memory storage is viewed as occurring once, after which the memory is permanently stored and insensitive to disruption by protein synthesis inhibitors or other amnesia-inducing treatments (4). However, considerable evidence has emerged indicating that memory becomes newly dependent on protein synthesis after reactivation (retrieval), a process called reconsolidation (4-6). For example, we and others have used Pavlovian fear conditioning to study the consolidation and reconsolidation of associative memories (6)(7)(8)(9)(10)(11)(12)(13)(14). In fear conditioning, a neutral conditioned stimulus (CS), such as an auditory tone, is paired with an unconditioned stimulus (US), typically consisting of electric foot shock. After the pairing, the CS has the capacity to elicit conditioned fear responses, often measured in terms of immobility or freezing behavior (15). Blockade of protein synthesis in the lateral and basal nuclei of the amygdala (LBA), the presumed site of fear memory formation and storage (16), after training disrupts the consolidation of fear memories (17), and blockade after retrieval of consolidated memories disrupts their reconsolidation (6, 12).In life, memories are typically not stored in isolation of other memories but instead are believed to be integrated into complex associative networks, such that activation of one element of an association leads to activation of related elements (18). A key question is whether reactivation of one component of an associative network renders all memories in the network labile and sensitive to disruption. Most studies of reconsolidation to date have either foc...

Intrusive memories resulting from an emotional trauma are a defining feature of posttraumatic stress disorder (PTSD). Existing studies demonstrate that an increase of noradrenergic activity during a life-threatening event contributes to strengthening or "overconsolidation" of the memory for trauma. The lateral nucleus of the amygdala (LA) is critical for fear learning. Using classical fear conditioning in rats, we have recently demonstrated that noradrenergic blockade in the LA following reactivation of fear memory by retrieval disrupts memory reconsolidation and lastingly impairs fear memory. This suggests that noradrenergic blockade may be useful in attenuating traumatic memories, even well-consolidated old memories, in PTSD.

Background: Posttraumatic stress disorder (PTSD) is associated with enhanced noradrenergic activity. Animal and human studies demonstrate that noradrenergic stimulation augments consolidation of fear learning. Retrieval of well-established memories by presenting a learned fear cue triggers reconsolidation processes during which memories may be updated, weakened, or strengthened. We previously reported that noradrenergic blockade in the rat amygdala impairs reconsolidation of fear memories. Here we investigated the effects of noradrenergic enhancement on reconsolidation of learned fear. Methods: Using auditory fear conditioning in rats, we tested the effects of postretrieval intraamygdala infusion of the b-adrenergic receptor agonist isoproterenol or the antagonist propranolol on conditioned fear in the amygdala. Results: A single intraamygdala infusion of isoproterenol following a retrieval of a well-consolidated memory enhanced fear memory elicited by the learned fear stimulus and impaired extinction of this memory 48 hr later. Intraamygdala infusion of the b-adrenergic receptor antagonist propranolol following a consecutive retrieval trial blocked the enhancing effects of isoproterenol on fear memory. Conclusions: Postretrieval b-adrenergic stimulation in the amygdala enhances reconsolidation of fear memories, making them resistant to extinction. Noradrenergic augmentation during retrieval of fear memories may thus contribute to persistence and severity of traumatic memories. Reconsolidation may be a useful tool in understanding the pathology of PTSD and may thus help in developing new and in modifying existing treatments of traumatic memories. Depression and Anxiety 28:186-193, 2011.

Emotional trauma is transmitted across generations. For example, children witnessing their parent expressing fear to specific sounds or images begin to express fear to those cues. Within normal range, this is adaptive, although pathological fear, such as occurs in posttraumatic stress disorder or specific phobias, is also socially transmitted to children and is thus of clinical concern. Here, using a rodent model, we report a mother-to-infant transfer of fear to a novel peppermint odor, which is dependent on the mother expressing fear to that smell in pups' presence. Examination of pups' neural activity using c-Fos early gene expression and 14 C 2-deoxyglucose autoradiography during mother-to-infant fear transmission revealed lateral and basal amygdala nuclei activity, with a causal role highlighted by pharmacological inactivation of pups' amygdala preventing the fear transmission. Maternal presence was not needed for fear transmission, because an elevation of pups' corticosterone induced by the odor of the frightened mother along with a novel peppermint odor was sufficient to produce pups' subsequent aversion to that odor. Disruption of axonal tracts from the Grueneberg ganglion, a structure implicated in alarm chemosignaling, or blockade of pups' alarm odor-induced corticosterone increase prevented transfer of fear. These memories are acquired at younger ages compared with amygdala-dependent odorshock conditioning and are more enduring following minimal conditioning. Our results provide clues to understanding transmission of specific fears across generations and its dependence upon maternal induction of pups' stress response paired with the cue to induce amygdala-dependent learning plasticity. Results are discussed within the context of caregiver emotional responses and adaptive vs. pathological fears social transmission.necklace glomeruli | pheromone | olfaction | PTSD | social referencing

When reactivated, memories enter a labile, protein synthesis-dependent state, a process referred to as reconsolidation. Here, we show in rats that fear memory retrieval produces a synaptic potentiation in the lateral amygdala that is selective to the reactivated memory, and that disruption of reconsolidation is correlated with a reduction of synaptic potentiation in the lateral amygdala. Thus, both retrieval and reconsolidation alter memories via synaptic plasticity at selectively targeted synapses.

Learning about potential threats is critical for survival. Learned fear responses are acquired either through direct experiences or indirectly through social transmission. Social fear learning (SFL), also known as vicarious fear learning, is a paradigm successfully used for studying the transmission of threat information between individuals. Animal and human studies have begun to elucidate the behavioral, neural and molecular mechanisms of SFL. Recent research suggests that social learning mechanisms underlie a wide range of adaptive and maladaptive phenomena, from supporting flexible avoidance in dynamic environments to intergenerational transmission of trauma and anxiety disorders. This review discusses recent advances in SFL studies and their implications for basic, social and clinical sciences.