Research Article

A Neural Circuit for Memory Specificity and Generalization

Science  15 Mar 2013:
Vol. 339, Issue 6125, pp. 1290-1295
DOI: 10.1126/science.1229534

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The Thalamus in Fear and Memory

The medial prefrontal cortex (mPFC) mediates the cognitive control of many high-level brain functions. However, it is unclear which synaptic projections from the mPFC to subcortical regions are critical for maintaining the proper balance between retention and generalization of fear memory details. Using an array of behavioral, physiological, and anatomical techniques, Xu and Südhof (p. 1290) describe a neural circuit that controls memory generalization and specificity. This circuit involves the nucleus reuniens (NR), a thalamic nucleus of largely unknown function. Optogenetic activation of NR neurons in awake behaving mice revealed the role of the NR in fear memory generalization.


Increased fear memory generalization is associated with posttraumatic stress disorder, but the circuit mechanisms that regulate memory specificity remain unclear. Here, we define a neural circuit—composed of the medial prefrontal cortex, the nucleus reuniens (NR), and the hippocampus—that controls fear memory generalization. Inactivation of prefrontal inputs into the NR or direct silencing of NR projections enhanced fear memory generalization, whereas constitutive activation of NR neurons decreased memory generalization. Direct optogenetic activation of phasic and tonic action-potential firing of NR neurons during memory acquisition enhanced or reduced memory generalization, respectively. We propose that the NR determines the specificity and generalization of memory attributes for a particular context by processing information from the medial prefrontal cortex en route to the hippocampus.

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