Anteromedial thalamus gates the selection and stabilization of long-term memories

Toader, Andrew C.; Regalado, Josue M.; Li, Yan Ran; Terceros, Andrea; Yadav, Nakul; Kumar, Suraj; Satow, Sloane; Hollunder, Florian; Bonito‐Oliva, Alessandra; Rajasethupathy, Priyamvada

doi:10.1016/j.cell.2023.02.024

Cited by 28 publications

(10 citation statements)

References 63 publications

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“…The hippocampus is a crucial structure in the brain and is mainly composed of the dentate gyrus and cornu ammonis (CA3, CA2, and CA1) subregions [ 35 ], and memories initially formed in the hippocampus gradually stabilize to the cortex over weeks to months for long-term storage [ 36 ]. The hippocampal CA3 subregion plays a crucial role in the storage, retrieval, and processing of both spatial and nonspatial information [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Terahertz Photons Improve Cognitive Functions in Posttraumatic Stress Disorder

Yu,

Wu,

Yang

et al. 2023

Research

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Posttraumatic stress disorder (PTSD) is a serious psychosis leading to cognitive impairment. To restore cognitive functions for patients, the main treatments are based on medication or rehabilitation training but with limited effectiveness and strong side effects. Here, we demonstrate a new treatment approach for PTSD by using terahertz (THz) photons stimulating the hippocampal CA3 subregion. We verified that this method can nonthermally restore cognitive function in PTSD rats in vivo. After THz photon irradiation, the PTSD rats’ recognitive index improved by about 10% in a novel object recognition test, the PTSD rats’ accuracy improved by about 100% in a shuttler box test, the PTSD rats’ numbers to identify target box was about 5 times lower in a Barnes maze test, and the rate of staying in new arm increased by approximately 40% in a Y-maze test. Further experimental studies found that THz photon (34.5 THz) irradiation could improve the expression of NR2B (increased by nearly 40%) and phosphorylated NR2B (increased by about 50%). In addition, molecular dynamics simulations showed that THz photons at a frequency of 34.5 THz are mainly absorbed by the pocket of glutamate receptors rather than by glutamate molecules. Moreover, the binding between glutamate receptors and glutamate molecules was increased by THz photons. This study offers a nondrug, nonthermal approach to regulate the binding between the excitatory neurotransmitter (glutamate) and NR2B. By increasing synaptic plasticity, it effectively improves the cognitive function of animals with PTSD, providing a promising treatment strategy for NR2B-related cognitive disorders.

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Section: Discussionmentioning

confidence: 99%

Terahertz Photons Improve Cognitive Functions in Posttraumatic Stress Disorder

Yu,

Wu,

Yang

et al. 2023

Research

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“…For all analysis, this dF/F was then normalized by z-scoring the entire time series across a session. To identify statistically significant transients, we first calculated an estimate of the noise for each cell using a custom MATLAB script, with a previously described method 56,57 . In essence, we identified the limiting noise cutoff level for a given cell using time periods that are unlikely to contain neural events, and then defined a transient as significant if it reached above at least 3σ of this estimated noise level.…”

Section: Methodsmentioning

confidence: 99%

Neural activity ramps in frontal cortex signal extended motivation during learning

Regalado,

Asensio,

Haunold

et al. 2023

Preprint

Self Cite

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Learning requires the ability to link actions to outcomes. How motivation facilitates learning is not well understood. We designed a behavioral task in which mice self-initiate trials to learn cue-reward contingencies and found that the anterior cingulate region of the prefrontal cortex (ACC) contains motivation-related signals to maximize rewards. In particular, we found that ACC neural activity was consistently tied to trial initiations where mice seek to leave unrewarded cues to reach reward-associated cues. Notably, this neural signal persisted over consecutive unrewarded cues until reward associated cues were reached, and was required for learning. To determine how ACC inherits this motivational signal we performed projection specific photometry recordings from several inputs to ACC during learning. In doing so, we identified a ramp in bulk neural activity in orbitofrontal cortex (OFC) -to-ACC projections as mice received unrewarded cues, which continued ramping across consecutive unrewarded cues, and finally peaked upon reaching a reward associated cue, thus maintaining an extended motivational state. Cellular resolution imaging of OFC confirmed these neural correlates of motivation, and further delineated separate ensembles of neurons that sequentially tiled the ramp. Together, these results identify a mechanism by which OFC maps out task structure to convey an extended motivational state to ACC to facilitate goal-directed learning.

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“…Current animal models of memory are not designed to allow the direct study of the neural substrates of retrieval not confounded by sensory cues or the decision to act. First, current experimental approaches typically engage retrieval by presenting external cues such as those found in a particular spatial context 1,18–20 . These cues can strongly influence patterns of brain activity, including spiking in brain regions like the hippocampus 6 that contribute to memory formation and retrieval 19 .…”

Section: Main Textmentioning

confidence: 99%

Closed-loop modulation of remote hippocampal representations with neurofeedback

Coulter,

Gillespie,

Chu

et al. 2024

Preprint

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Humans can remember specific events without acting on them and can influence which memories are retrieved based on internal goals. However, current animal models of memory typically present sensory cues to trigger retrieval and assess retrieval based on action. As a result, it is difficult to determine whether measured patterns of neural activity relate to the cue(s), the retrieved memory, or the behavior. We therefore asked whether we could develop a paradigm to isolate retrieval-related neural activity in animals without retrieval cues or the requirement of a behavioral report. To do this, we focused on hippocampal "place cells." These cells primarily emit spiking patterns that represent the animal's current location (local representations), but they can also generate representations of previously visited locations distant from the animal's current location (remote representations). It is not known whether animals can deliberately engage specific remote representations, and if so, whether this engagement would occur during specific brain states. So, we used a closed-loop neurofeedback system to reward expression of remote representations that corresponded to uncued, experimenter-selected locations, and found that rats could increase the prevalence of these specific remote representations over time; thus, demonstrating memory retrieval modulated by internal goals in an animal model. These representations occurred predominately during periods of immobility but outside of hippocampal sharp-wave ripple (SWR) events. This paradigm enables future direct studies of memory retrieval mechanisms in the healthy brain and in models of neurological disorders.

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Anteromedial thalamus gates the selection and stabilization of long-term memories

Cited by 28 publications

References 63 publications

Terahertz Photons Improve Cognitive Functions in Posttraumatic Stress Disorder

Terahertz Photons Improve Cognitive Functions in Posttraumatic Stress Disorder

Neural activity ramps in frontal cortex signal extended motivation during learning

Closed-loop modulation of remote hippocampal representations with neurofeedback

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