From contextual fear to a dynamic view of memory systems

Cognitive, Affective, & Behavioral Neuroscience, 2001

The context in which events occur can be represented as both (1) a set of independent features, the feature representation view, and (2) a set of features bound into a unitary representation, the conjunction representation view. It is assumed that extrahippocampal (e.g., neocortical) areas provide a basis for feature representations, but the hippocampal formation makes an essential contribution to the automatic storage of conjunctive representations. We develop this dual-representation view and explore its implications for hippocampal contributions to contextual fear conditioning processes. To this end, we discuss how our framework can resolve some of the conflicts in the recent literature relating the hippocampus to contextual fear conditioning. We also present new data supporting the role of a key mechanism afforded by conjunctive representations-pattern completion (the ability of a subset of a memory pattern to activate the complete memory)-in contextual fear conditioning. As is implied by this mechanism, we report that fear can be conditioned to the memory representation of a context that is not actually present at the time of shock. Moreover, this result is predicted by our computational model of cortical and hippocampal function. We suggest that pattern completion demonstrated in animals and by our model provides a mechanistic bridge to human declarative memory.

…, 2004

Much attention has been paid to the associative processes that are necessary to fuse together representations of the various components of an episodic memory. In the present study, we focus on the processes involved in the formation of lasting representations of the individual components that make up a fear-conditioning episode. In onetrial contextual fear conditioning experiments, weak conditioning to context occurs if the shock is delivered immediately following placement of the animal in a novel conditioning apparatus, a phenomenon known as the immediate shock deficit. We show that the immediate shock deficit in mice may be alleviated by pre-exposure to either the context or shock. In using this approach to temporally dissect a contextual fear-conditioning task into its constituent representational and associative processes, we are able to examine directly the processes that are important for formation of lasting representations of the context conditioned stimulus (CS) or unconditioned stimulus (US). Our data indicate that the formation of a lasting representation of the context or shock engages protein synthesis-dependent processes. Furthermore, genetic disruption of cAMP-responsive element binding protein (CREB), a transcription factor that regulates the synthesis of new proteins required for long-term memory, disrupts the formation of lasting context memories. We go on to show that the stress hormone epinephrine modulates the consolidation of a context memory, and reverses consolidation deficits in the CREB-deficient mice. Finally we show that disrupting either NMDA or calcium/calmodulin-dependent kinase II (CaMKII) function impairs consolidation of context memories. Together, these data suggest that this approach is particularly suited for the characterization of molecular and cellular processes underlying the formation of stimulus representations.

The Journal of …, 2006

Lesions of the rodent hippocampus invariably abolish context fear memories formed in the recent past but do not always prevent new learning. To better understand this discrepancy, we thoroughly examined the acquisition of context fear in rats with pretraining excitotoxic lesions of the dorsal hippocampus. In the first experiment, animals received a shock immediately after placement in the context or after variable delays. Immediate shock produced no context fear learning in lesioned rats or controls. In contrast, delayed shock produced robust context fear learning in both groups. The absence of fear with immediate shock occurs because animals need time to form a representation of the context before shock is presented. The fact that it occurs in both sham and lesioned rats suggests that they learn about the context in a similar manner. However, despite learning about the context in the delay condition, lesioned rats did not acquire as much fear as controls. The second experiment showed that this lesion-induced deficit could be overcome by increasing the number of conditioning trials. Lesioned animals learned normally after multiple shocks, regardless of freezing level or trial spacing. The last experiment showed that animals with complete hippocampus lesions could also learn about the context, although the same lesions produced devastating retrograde amnesia. These results demonstrate that alternative systems can acquire context fear but do so less efficiently than the hippocampus.

Hippocampus, 2002

In a recent article that appeared in Hippocampus, we reviewed findings supporting a mnemonic role for the dorsal hippocampus (DH) in Pavlovian (contextual and tone) fear conditioning . We also detailed a view that has emerged over the years from this work that suggests that the hippocampus plays a highly selective role in the acquisition and temporary storage of contextual representations, as opposed to a role in conditional stimulus-unconditional stimulus (CS-US) associations or in permanent storage for which the amygdala has been heavily implicated (Kim and . Because the evidence that DH lesions produce a temporally graded retrograde amnesia selective for contextual fear that accords well with declarative memory deficits in amnesic humans, we have further argued this may be a good model system with which to study the transformation of memory from a hippocampus-dependent to a hippocampus-independent (cortical) state (i.e., consolidation) .

Living organism acquire long-lasting memories for threatening events called fear memories. Recall of fear memory in presence or absence of harmful stimuli is dependent of re-exposure to associated cue or context to make the organism able to become alert for coming threat if arise again in future. In present study behavioral outcomes were investigated in response to paired and unpaired CS-US presentation using Pavlovian classical conditioning model. The fear response during fear acquisition (experiencing harmful-fear stimulus) was found independent of paired cue/context presentation while fear response during recall of fear memory was dependent of paired cue or context presentation. Results suggested that fear memory formation require association of harmful stimulus with cue and without cue the animal was unable to reproduce the fear response if threatening stimulus was absent.

In a recent article that appeared in Hippocampus, we reviewed findings supporting a mnemonic role for the dorsal hippocampus (DH) in Pavlovian (contextual and tone) fear conditioning . We also detailed a view that has emerged over the years from this work that suggests that the hippocampus plays a highly selective role in the acquisition and temporary storage of contextual representations, as opposed to a role in conditional stimulus-unconditional stimulus (CS-US) associations or in permanent storage for which the amygdala has been heavily implicated (Kim and . Because the evidence that DH lesions produce a temporally graded retrograde amnesia selective for contextual fear that accords well with declarative memory deficits in amnesic humans, we have further argued this may be a good model system with which to study the transformation of memory from a hippocampus-dependent to a hippocampus-independent (cortical) state (i.e., consolidation) .

Neuroscience & Biobehavioral Reviews

Arousing information is oriented toward automatically and benefits from rapid processing. Prioritization of processing (Pessoa, 2005) Arousing information is more likely to be prioritized for processing than neutral information. Cue-Utilization Hypothesis (Easterbrook, 1959) As emotional arousal increases, there is a restriction in the range of cues that are used or attended. Encoding and post-encoding Post-Stimulus Elaboration (Christianson, 1992) Arousing information is elaborated and rehearsed. Memory Trade-Offs; Weapon-Focus Effect (Barrett, 2006; Loftus et al., 1987) Some aspects of an arousing event are remembered well, at the expense of other aspects. Arousal Biased Competition (Mather and Sutherland, 2011) Arousal creates a "winner-take-more" state, biasing processing toward the information that gains high priority via bottom-up or top-down influences. Mediation Theory of Emotional Memory Enhancement (Talmi, 2013) Arousal re-allocates attentional and organizational resources. Emotional Binding (Yonelinas and Ritchey, 2015) Item-emotion binding by amygdala leads to slower forgetting than item-context binding by hippocampus. Storage Memory Modulation (McGaugh, 2000) Arousal activates the amygdala and engages adrenergic and cortisol systems to promote memory storage. Retrieval Response Bias (Dougal and Rotello, 2007) Arousal causes individuals to be more liberal in endorsing a memory. Subjective Sense of Recollection (Phelps and Sharot, 2008) Amygdala engagement during retrieval biases individuals to experience a sense of recollection.

Frontiers in Behavioral Neuroscience, 2011

retrieval," "gating" of inhibition, etc. These are essentially psychological constructs and do not provide much guidance for implementation at a neural level.

2016

Fear conditioning is a successful paradigm for studying neural substrates of emotional learning. In this thesis, two computational models of the underlying neural circuitry are presented. First, the effects of changes in neuronal membrane conductance on input processing are analyzed in a biologically realistic model. We show that changes in tonic inhibitory conductance increase the responsiveness of the network to inputs. Then, the model is analyzed from a functional perspective and predictions that follow from this proposition are discussed. Next, a systems level model is presented based on a recent high-level approach to conditioning. It is proposed that the interaction between fear and extinction neurons in the basal amygdala is a neural substrate of the switching between latent states, allowing the animal to infer causal structure. Important behavioral and physiological results are reproduced and predictions and questions that follow from the main hypothesis are considered.

2010

The basolateral amygdala (BLA) is thought to be essential for fear learning. However, extensive training can overcome the loss of conditional fear evident following lesions and inactivation of the BLA. Such results suggest the existence of a primary BLA-dependent and a compensatory BLA-independent neural circuit. We tested the hypothesis that the bed nuclei of the stria terminalis (BST) provides this compensatory plasticity. Using extensive context-fear conditioning, we demonstrate that combined BLA and BST lesions prevented fear acquisition and expression. Additionally, protein synthesis in the BST was critical only for consolidation of BLA-independent but not BLA-dependent fear. Moreover, fear acquired after BLA lesions resulted in greater activation of BST regions that receive hippocampal efferents. These results suggest that the BST is capable of functioning as a compensatory site in the acquisition and consolidation of context-fear memories. Unlocking such neural compensation holds promise for understanding situations when brain damage impairs normal function or failure to regulate compensatory sites leads to anxiety disorders. amygdala | basolateral amygdala | context | plasticity | bed nucleus of the stria terminalis A largely supported view in the neuroscience of associative memory is the existence of essential neural circuits that have the capacity to learn, retain, and retrieve specific classes of experience 1-7). For example, in reflexive motor learning or Pavlovian eyeblink-conditioning, the integration of sensory stimuli within the cerebellar interpositus nuclei are required for the acquisition, retention, and retrieval conditional responses (8). Similarly, the striatum is considered critical for habit learning (9, 10) and the hippocampus essential for spatial learning (11). In fearconditioning, a circuit centered around the basolateral amygdala complex (BLA; consisting of the lateral amygdala, basomedial, basolateral, and posterior nuclei) is viewed essential for the acquisition and expression of fear memories (12-16). The importance of the BLA for fear memory has been supported by numerous studies showing that disruption of protein synthesis, NMDA receptor function, neuronal activity, synaptic transmission, and plasticity all prevent the establishment of fear memories (14-18).