Biology subjects

Tuna, T.

Publications and source records attributed to Tuna, T..

3 recordsLinked to original sources

bioRxiv2025

Theta-paced stimulation of the thalamic nucleus reuniens en-trains mPFC-HPC oscillations and facilitates the acquisition of extinction memories

BackgroundThe nucleus reuniens (RE) is a midline thalamic nucleus interconnecting the medial prefrontal cortex (mPFC) and the hippocampus (HPC), structures known to be involved in aversive memory processes. Recent work indicates that the RE plays a critical role in the acquisition and retrieval of fear extinction memories. Functional inactivation of the RE impairs both mPFC-HPC coherence and extinction memory. Here we examine whether imposing theta activity on the RE entrains oscillations in the mPFC and HPC and facilitates extinction learning. MethodsTo deliver theta-paced (8 Hz) optogenetic stimulation, we expressed an excitatory opsin, (channelrhodopsin; AAV9-CaMKIIa-hChR2(H134R)-mCherry) or control virus (AAV9-CaMKIIa-mCherry) in the RE in male and female rats. A single optic fiber targeting the RE was implanted during the same surgery. After recovery, animals underwent auditory fear conditioning, extinction training, and an extinction retrieval test, each separated by 24-h. During extinction training, conditioned stimuli (CS) presentations were paired with 8-Hz sinusoidal optostimulation (473 nM, 10 mW) of the RE. In another experiment, we recorded local field potentials (LFPs) from the mPFC and dorsal HPC during using these behavioral procedures. ResultsTheta-paced stimulation of the RE during extinction training significantly decreased freezing behavior compared to the control group. Notably, the reduction in conditioned behavior was evident during the subsequent stimulation-free retrieval test. This reveals that RE stimulation during extinction not only suppresses conditioned fear responses acutely, but also facilitates the acquisition of long-term extinction memories. Theta-paced RE stimulation markedly enhanced both neural activity and entrained theta oscillations in the mPFC and dHPC. ConclusionThis work suggests that the RE oscillatory activity is critical for the acquisition of extinction memories through the modulation of hippocampal-prefrontal network dynamics. In the future, RE theta-paced stimulation can be an important therapeutic tool by strengthening extinction memories.

neuroscience↗

bioRxiv2025

Hippocampal-prelimbic coupling during context-dependent extinction retrieval in rats

After fear conditioning, repeated presentation of the conditioned stimulus (CS) alone produces a context-dependent extinction of learned fear. The hippocampus has a critical role in this process, but the mechanism by which contextual information encoded by the hippocampus leads to fear suppression is unknown. We hypothesize that contextual information encoded by the dorsal hippocampus supports the recall of extinction memory by the medial prefrontal cortex (mPFC). To test this hypothesis, we evaluated the oscillatory coherence and directional coupling of the hippocampus and mPFC during context-dependent extinction retrieval in a previously published experiment. In this experiment, male and female rats were subjected to auditory fear conditioning followed by fear extinction and extinction retrieval procedures. Previous analyses focused on oscillatory coupling during the CS; here, we performed new analyses to assess hippocampal-prefrontal coupling in the context in which extinction occurred. We found that, after extinction, re-exposing the animals to the extinction context produces a marked increase in dorsal hippocampal theta (6-8 Hz) oscillations. This increase was associated with enhanced coherence with the prelimbic (PL), but not the infralimbic (IL), division of the mPFC. Moreover, Granger causality analyses revealed that hippocampal theta oscillations preceded theta in the PL throughout the extinction retrieval session. This effect emerged during exposure to the extinction context and persisted during the presentation of the CSs and the expression of freezing behavior. Interestingly, this pattern of coherence was not observed in the IL. These results reveal that oscillatory coupling between the dorsal hippocampus and PL facilitates the context-dependent retrieval of the extinguished fear memory.

neuroscience↗

bioRxiv2025

Associative coding of conditioned fear in the thalamic nucleus reuniens in rodents and humans

The nucleus reuniens (RE) is a midline thalamic structure interconnecting the medial prefrontal cortex (mPFC) and the hippocampus (HPC). Recent work in both rodents and humans implicates the RE in the adaptive regulation of emotional memories, including the suppression of learned fear. However, the neural correlates of aversive learning in the RE of rodents and humans remains unclear. To address this, we recorded RE activity in humans (BOLD fMRI) and rats (fiber photometry) during Pavlovian fear conditioning and extinction. In both rats and humans, we found that conditioned stimulus (CS)-evoked activity in RE reflects the associative value of the CS. In rats, we additionally found that spontaneous neural activity in RE tracks defensive freezing and shows anticipatory increases in calcium activity that precede the termination of freezing behavior. Single-unit recordings in rats confirmed that individual RE neurons index both the associative value of the CS and defensive behavior transitions. Moreover, distinct neuronal ensembles in the RE encode fear versus extinction memories. These findings suggest a conserved role of the RE across species in modulating defensive states and emotional memory processes, providing a foundation for future translational research on fear-related disorders.

neuroscience↗