A Neural Circuit for Memory Specificity and Generalization

By Wei Xu, T. Sūdhof. Science, 2013

605 citations recorded by the source corpus.

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. Projections to and from the nucleus reunions in the thalamus regulate the specificity of contextual fear memory. 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.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

View Paper: https://www.semanticscholar.org/paper/4c1372141451d130a189d7f1a845e7731e3c48ea

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In Cellular and Molecular Neuroscience

In Cognitive Neuroscience

Citations in the corpus

Natural neural projection dynamics underlying social behavior. (2014, positive): “With this approach (previously used to retrogradely target circuits; Gradinaru et al., 2010; Xu and Südhof, 2013), ChR2 is targeted to the subpopulation of VTA cells terminating in NAc.”
Thalamic neuromodulation and its implications for executive networks (2014, background): “New experimental strategies to manipulate the activity of specific pathways (Xu and Südhof, 2013) offer more selective approaches to attack this question.”
Loss of Ensemble Segregation in Dentate Gyrus, but not in Somatosensory Cortex, during Contextual Fear Memory Generalization (2016, background): “In fact, a recent optogenetic study reported that the activity of the nucleus reuniens during acquisition affected the specificity of contextual memory (Xu and Südhof, 2013).”
Closed-loop and activity-guided optogenetic control. (2015, positive): “The absence of photosensitivity in diverse off-target afferent fibers when typical AAV-based projection targeting is carried out already addresses a major synchrony confound of electrical stimulation (Creed et al., 2015).”
Interplay of hippocampus and prefrontal cortex in memory (2013, neutral): “There is also a subcortical route through the thalamus (nucleus reuniens) directly to the hippocampus, by which the prefrontal cortex could control the specificity of memory retrieval [7].”
The content of hippocampal “replay” (2018, background): “…thought (Attardo et al., 2015; Rubin et al., 2015; Ziv et al., 2013), the ability to flexibly add neurons to an existing framework may facilitate, rather than hinder, rapid acquisition of information (Tse et al., 2007), or it may serve as a mechanism allowing for generalization (Xu & Sudhof, 2013).”