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Stimulus-specific enhancement of fear extinction during slow-wave sleep (Jana Husse)

AUTHORS: Katherina K Hauner, James D Howard, Christina Zelano & Jay A Gottfried

ABSTRACT: Sleep can strengthen memory for emotional information, but whether emotional memories can be specifically targeted and modified during sleep is unknown. In human subjects who underwent olfactory contextual fear conditioning, re-exposure to the odorant context in slow-wave sleep promoted stimulus-specific fear extinction, with parallel reductions of hippocampal activity and reorganization of amygdala ensemble patterns. Thus, fear extinction may be selectively enhanced during sleep, even without re-exposure to the feared stimulus itself.

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Reactivation of Neural Ensembles during the Retrieval of Recent and Remote Memory (Gisella Vetere)

AUTHORS: Kaycie K. Tayler, Kazumasa Z. Tanaka, Leon G. Reijmers, and Brian J. Wiltgen

ABSTRACT: Episodic memories are encoded within hippocampal and neocortical circuits. Retrieving these memories is assumed to involve reactivation of neural ensembles that were established during learning. Although it has been possible to follow the activity of individual neurons shortly after learning, it has not been possible to examine their activity weeks later during retrieval. We addressed this issue by using a stable form of GFP (H2B-GFP) to permanently tag neurons that are active during contextual fear conditioning.


H2B-GFP expression in transgenic mice was increased by learning and could be regulated by doxycycline (DOX). Using this system, we found a large network of neurons in the hippocampus, amygdala, and neocortex that were active during context fear conditioning and subsequent memory retrieval 2 days later. Reactivation was contingent on memory retrieval and was not observed when animals were trained and tested in different environments. When memory was retrieved several weeks after learning, reactivation was altered in the hippocampus and amygdala but remained unchanged in the cortex.


Retrieving a recently formed context fear memory reactivates neurons in the hippocampus, amygdala, and cortex. Several weeks after learning, the degree of reactivation is altered in hippocampal and amygdala networks but remains stable in the cortex.

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Memory recall and modifications by activating neurons with elevated CREB (Axel Guskjolen)

AUTHORS: Jieun Kim, Jeong-Tae Kwon, Hyung-Su Kim, Sheena A Josselyn & Jin-Hee Han

ABSTRACT: Memory is supported by a specific ensemble of neurons distributed in the brain that form a unique memory trace. We previously showed that neurons in the lateral amygdala expressing elevated levels of cAMP response-element binding protein are preferentially recruited into fear memory traces and are necessary for the expression of those memories. However, it is unknown whether artificially activating just these selected neurons in the absence of behavioral cues is sufficient to recall that fear memory. Using an ectopic rat vanilloid receptor TRPV1 and capsaicin system, we found that activating this specific ensemble of neurons was sufficient to recall established fear memory. Furthermore, this neuronal activation induced a reconsolidation-like reorganization process, or strengthening of the fear memory. Thus, our findings establish a direct link between the activation of specific ensemble of neurons in the lateral amygdala and the recall of fear memory and its subsequent modifications.

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Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer’s disease (Adelaide Yiu)

AUTHORS: Usman A Khan, Li Liu, Frank A Provenzano, Diego E Berman, Caterina P Profaci, Richard Sloan, Richard Mayeux, Karen E Duff & Scott A Small

ABSTRACT: The entorhinal cortex has been implicated in the early stages of Alzheimer’s disease, which is characterized by changes in the tau protein and in the cleaved fragments of the amyloid precursor protein (APP). We used a high-resolution functional magnetic resonance imaging (fMRI) variant that can map metabolic defects in patients and mouse models to address basic questions about entorhinal cortex pathophysiology. The entorhinal cortex is divided into functionally distinct regions, the medial entorhinal cortex (MEC) and the lateral entorhinal cortex (LEC), and we exploited the high-resolution capabilities of the fMRI variant to ask whether either of them was affected in patients with preclinical Alzheimer’s disease. Next, we imaged three mouse models of disease to clarify how tau and APP relate to entorhinal cortex dysfunction and to determine whether the entorhinal cortex can act as a source of dysfunction observed in other cortical areas. We found that the LEC was affected in preclinical disease, that LEC dysfunction could spread to the parietal cortex during preclinical disease and that APP expression potentiated tau toxicity in driving LEC dysfunction, thereby helping to explain regional vulnerability in the disease.


Hippocampal Binding of Novel Information with Dominant Memory Traces Can Support Both Memory Stability and Change (Xiaochen Hu)

AUTHORS: Donna J. Bridge and Joel L. Voss

ABSTRACT: Memory stability and change are considered opposite outcomes. We tested the counterintuitive notion that both depend on one process: hippocampal binding of memory features to associatively novel information, or associative novelty binding (ANB). Building on the idea that dominant memory features, or “traces,” are most susceptible to modification, we hypothesized that ANB would selectively involve dominant traces. Therefore, memory stability versus change should depend on whether the currently dominant trace is old versus updated; in either case, novel information will be bound with it, causing either maintenance (when old) or change (when updated). People in our experiment studied objects at locations within scenes (contexts). During reactivation in a new context, subjects moved studied objects to new locations either via active location recall or by passively dragging objects to predetermined locations. After active reactivation, the new object location became dominant in memory, whereas after passive reactivation, the old object location maintained dominance. In both cases, hippocampal ANB bound the currently dominant object-location memory with a context with which it was not paired previously (i.e., associatively novel). Stability occurred in the passive condition when ANB united the dominant original location trace with an associatively novel newer context. Change occurred in the active condition when ANB united the dominant updated object location with an associatively novel and older context. Hippocampal ANB of the currently dominant trace with associatively novel contextual information thus provides a single mechanism to support memory stability and change, with shifts in trace dominance during reactivation dictating the outcome.