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Nunez, L.

Publications and source records attributed to Nunez, L..

2 recordsLinked to original sources

Hippocampal-cingulate dynamics in the human brain link reinforcement-learning and memory

Reinforcement learning (RL) models describe how reward computations shape our choices, but whether the same computations also shape memory in the human brain is unclear. To address this question, we combined multi-areal intracranial recordings with computational modeling of reward and memory in neurosurgical patients. Patients played a gambling task in which decisions yielded monetary rewards tied to trial-unique images, followed immediately by a recognition test for those images. Model-derived positive reward prediction errors (RPEs) predicted later memory for each image. During feedback, multivariate high-frequency activity revealed the spatiotemporal evolution of RPE representations across distributed prefrontal cortex. During subsequent recognition, however, only anterior cingulate cortex (ACC) transiently reinstated RPE representations, and successful recognition specifically associated with hippocampal reinstatement of these ACC representations. Hippocampal-cingulate theta synchrony scaled with RPE during recognition, alongside hippocampal theta decoding of upcoming memory choices. Thus, the RL computations that guide decision-making also shape memory through hippocampal-cingulate circuit dynamics in the human brain.

neuroscience↗

An integrated RNA-centric imaging and omics approach reveals distinct properties and composition of neuronal RNA granules

RNA granules are essential regulators of post-transcriptional gene expression, enabling mRNA transport, localization, and local translation in neurons. The localized transcriptome is diverse; however, how different mRNAs are organized into granules for efficient localization and translation remains unknown. Here, we combine real-time endogenous single RNA imaging with protein and RNA proximity labeling to investigate two distinct endogenous neuronal mRNA granule populations, Actb and Arc, in stimulated primary hippocampal neurons. Using orthogonal RNA labeling systems in a dual knock-in mouse model, we show that Actb and Arc mRNAs are packaged into spatially segregated granules with distinct trafficking dynamics, localization kinetics, and responses to synaptic stimulation. Actb granules displayed rapid and sustained localization, whereas Arc granules showed delayed, transient recruitment, consistent with their respective roles in structural and activity-dependent plasticity. Proximity labeling reveals that these granules are distinct in their mRNA composition, despite sharing core RNA-binding proteins, suggesting that shared cis-regulatory elements within mRNA 3UTR regions drive selective co-packaging of mRNAs into unique granules. Together, these findings demonstrate that neuronal mRNAs are differentially sorted into molecularly and functionally distinct granules, providing a framework for understanding how precise spatio-temporal control of mRNA localization and translation is achieved across complex neuronal arbors.

neuroscience↗