Generation of a Synthetic Memory Trace

By Aleena R. Garner, David C Rowland, Sanghui Hwang, K. Baumgaertel, Bryan L. Roth, C. Kentros, M. Mayford. 2012

375 citations recorded by the source corpus.

Adding Artificial Associations In the mammalian cortex, there is significant spontaneous neural activity that is internally generated, rather than arising from sensory inputs, and this activity influences the processing of natural sensory stimuli. What role does this internally generated activity play in forming and accessing new memory representations? Using transgenic mice combined with controlled artificial activation of widely distributed neuronal ensembles associated with specific contexts, Garner et al. (p. 1513; see the Perspective by Morris and Takeuchi) investigated how spontaneous neuronal activity is integrated into a given context representation. Animals underwent fear conditioning in two distinct contexts. When a circuit in one context was artificially activated during fear conditioning in a separate context, a so-called “hybrid” memory was formed. This artificially stimulated network became a necessary component of the memory trace. These results are consistent with the emerging view that internally generated brain activity is not noise, but a coherent representation that can be incorporated into new associations and memories. The brains of transgenic mice incorporate experimentally generated neural activity into a memory trace. We investigated the effect of activating a competing, artificially generated, neural representation on encoding of contextual fear memory in mice. We used a c-fos–based transgenic approach to introduce the hM3Dq DREADD receptor (designer receptor exclusively activated by designer drug) into neurons naturally activated by sensory experience. Neural activity could then be specifically and inducibly increased in the hM3Dq-expressing neurons by an exogenous ligand. When an ensemble of neurons for one context (ctxA) was artificially activated during conditioning in a distinct second context (ctxB), mice formed a hybrid memory representation. Reactivation of the artificially stimulated network within the conditioning context was required for retrieval of the memory, and the memory was specific for the spatial pattern of neurons artificially activated during learning. Similar stimulation impaired recall when not part of the initial conditioning.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

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Citations in the corpus

Memory Engram Cells Have Come of Age. (2015, positive): “require pre-existing memories as a scaffold onto which distinct experiences can be incorporated to update the memory itself (Garner et al., 2012; Gershman et al., 2013; Tse et al., 2007).”
Memory engrams: Recalling the past and imagining the future (2020, background): “Mayford and colleagues (84) used a similar approach but tagged active neurons across the brain as mice explored a new context (context A).”
Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance (2015, positive): “…been used in mice for inducible expression of genes from the TRE (tetracycline response element, also called tetO) promoter in response to tTA (Tet-Off) or rtTA (Tet-On) activation (Garner et al., 2012; Gossen and Bujard, 1992; Mayford et al., 1996; Reijmers et al., 2007; Urlinger et al., 2000).”
The molecular and systems biology of memory. (2014, positive): “Garner et al. (2012) used this cfos-based genetic Cell 157, March 27, 2014 ª2014 Elsevier Inc. 173 Two transgenes are required.”
DREADDs for Neuroscientists (2016, background): “, 2012), memory (Garner et al., 2012), and social behaviors (Peñagarikano et al.”
The restless engram: consolidations never end. (2012, background): “The neurons associated with the previous experience of exploring BoxA were internally activated while the animal was learning an aversive association in BoxB, and in order to produce fear recall, the conjunctive activation of BoxA neurons was also required (Garner et al., 2012).”
Permanent Genetic Access to Transiently Active Neurons via TRAP: Targeted Recombination in Active Populations (2013, methodology): “1999), visualize active neurons in fixed or live tissue from transgenic animals (Barth et al., 2004; Smeyne et al., 1992; Wang et al., 2006), and manipulate the activities of IEG-expressing populations (Garner et al., 2012; Koya et al., 2009; Liu et al., 2012; Reijmers et al., 2007).”
Loss of Ensemble Segregation in Dentate Gyrus, but not in Somatosensory Cortex, during Contextual Fear Memory Generalization (2016, background): “…of neurons during contextual fear learning using this system have been shown to be sufficient and necessary for the contextual fear memory expression (Garner et al., 2012; Liu et al., 2012; Cowansage et al., 2014; Tanaka et al., 2014; Matsuo, 2015; Ohkawa et al., 2015; Yoshii et al., 2017).”
The content of hippocampal “replay” (2018, background): “Among several lines of investigation attempting to address this question (Garner et al., 2012; Josselyn et al., 2015; Ramirez et al., 2013; Tse et al., 2007), hippocampal ripples and ripple-based “replay” have emerged as strong candidate mechanisms which may facilitate both the initial storage and…”