Optogenetic stimulation of a hippocampal engram activates fear memory recall

A specific memory is thought to be encoded by a sparse population of neurons. These neurons can be tagged during learning for subsequent identification3 and manipulation. Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, the question of sufficiency remains: it is unclear whether it is possible to elicit the behavioural output of a specific memory by directly activating a population of neurons that was active during learning. Here we show in mice that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behaviour. We labelled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2) and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear-conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear-conditioned mice with cells labelled by enhanced yellow fluorescent protein instead of ChR2. Finally, activation of cells labelled in a context not associated with fear did not evoke freezing in mice that were previously fear conditioned in a different context, suggesting that light-induced fear memory recall is context specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.RIKEN Brain Science InstituteNational Institutes of Health (U.S.) (Grant R01-MH078821)National Institutes of Health (U.S.) (Grant P50-MH58880

A Rapid Late Enhancement MRI Protocol Improves Differentiation between Brain Tumor Recurrence and Treatment-Related Contrast Enhancement of Brain Parenchyma

Purpose: Differentiation between tumor recurrence and treatment-related contrast enhancement in MRI can be difficult. Late enhancement MRI up to 75 min after contrast agent application has been shown to improve differentiation between tumor recurrence and treatment-related changes. We investigated the diagnostic performance of late enhancement using a rapid MRI protocol optimized for clinical workflow. Methods: Twenty-three patients with 28 lesions suspected for glioma recurrence underwent MRI including T1-MPRAGE-series acquired 2 and 20 min after contrast agent administration. Early contrast series were subtracted from late contrast series using motion correction. Contrast enhancing lesions were retrospectively and independently evaluated by two readers blinded to the patients’ later clinical course and histology with or without the use of late enhancement series. Sensitivity, specificity, NPV, and PPV were calculated for both readers by comparing results of MRI with histological samples. Results: Using standard MR sequences, sensitivity, specificity, PPV, and NPV were 0.84, 0, 0.875, and 0 (reader 1) and 0.92, 0, 0.885, and 0 (reader 2), respectively. Early late enhancement increased sensitivity, specificity, PPV, and NPV to 1 for each value and for both readers. Inter-reader reliability increased from 0.632 (standard MRI sequences) to 1.0 (with early late enhancement). Conclusion: The described rapid late enhancement MRI protocol improves MRI-based discrimination between tumor tissue and treatment-related changes of the brain parenchyma