Projections from thalamic nucleus reuniens to hippocampal CA1 area enable context value updating

The ability to extinguish contextual fear in a changing environment is crucial for animal survival. The ‘classic’ neuronal circuit of contextual fear extinction includes the medial prefrontal cortex (mPFC), amygdala, and hippocampus. However, recent data also support the role of the thalamic nucleus reuniens (RE) in this process. Here, we aimed to determine whether the projections from RE to the dorsal hippocampal CA1 area (RE→dCA1) play a role in updating context-dependent memories and to characterize the underlying synaptic processes. We used chemogenetic manipulations and conducted ex vivo field recordings in mice to analyze the impact of RE afferents on synaptic transmission in the dCA1. Next, we employed virally mediated labeling of RE afferents in Thy1-GFP mice to analyze the RE buttons and dendritic spines (as a proxy for glutamatergic synapses) in dCA1 during contextual fear memory extinction. This approach was complemented by 3D electron microscopy to analyze synaptic changes with nano-scale resolution. Finally, using projection-specific chemogenetic manipulation, we tested the role of the RE→CA1 projection in the classic contextual fear extinction paradigm, as well as in the extinction of aversive and appetitive contextual memories in a close-to-ecological environment of IntelliCages. Overall, our data demonstrate that RE regulates synaptic transmission in the stratum oriens (SO) and lacunosum-moleculare of the CA1 area (SLM). Extinction of contextual fear induces synaptic plasticity in these regions. However, only the changes in SLM are specific for the dendrites innervated by RE. Finally, we demonstrate that the RE→dCA1 pathway contributes to updating contextual memories independent of their valence. ### Competing Interest Statement The authors have declared no competing interest.