Jean-Christophe Cassel: A non-exclusive role for the ventral midline thalamus in systems-level consolidation of memories: older, recent and preliminary findings

Abstract

The ventral midline thalamus encompasses two small nuclei named reuniens (Re) and rhomboid (Rh). Each of them is bi-directionally connected with the medial prefrontal cortex (mPFC) and CA1 of the hippocampus (HPC). This connectivity patter suggests that the ReRh nuclei might be a crossroad for information exchange between the HPC and the mPFC. Older findings: following fiber-sparing lesions of the nuclei, rats acquire correctly a spatial and a contextual memory task, which they remember at a short post-acquisition delay (recent memory), but have forgotten at a later one (remote memory). The lesion might have disrupted systems-level consolidation of both memories, a process by which a memory initially supported by hippocampal modules is progressively ‘transferred’ to cortical ones. If so, HPC and mPFC plasticity supporting memory persistence should be altered by the lesion. Recent findings: Again after fiber-sparing lesions of the ReRh, brain sections from rats trained in the spatial task were analyzed for spine density quantifications and c-Fos expression. In controls, learning triggered a rapid increase of hippocampal spine density (detected at recent and remote time points), and a delayed increase of mPFC spine density (detected only at the remote time point). Both phenomena were absent in rats with ReRh lesions.

Furthermore, at the remote time point, a retrieval and delay-triggered gain of c-Fos expression in the mPFC of controls was not observed in the rats with lesions. Thus, ReRh lesions alter plasticity mechanisms supporting spatial memory persistence in both the HPC and mPFC. But the role of these nuclei goes beyond systemic consolidation. Indeed, we also showed that the ReRh were involved in set-shifting processes during a spatial navigation task, that permanent lesions and acute DREADD-mediated inhibition altered. Preliminary findings: we are currently trying to understand the contribution of the different links in the mPFC<->ReH<->HPC connection circuit to the processes affected by the fiber-sparing lesion. To this end, we have used an approach based on the activation of a caspase in a cre recombinase-dependent manner within the mPFC->ReRh projection neurons. We just got out of a methodological trap (a few words will be said) before showing a first encouraging result in the set-shifting task.

Duration of the talk:

Approx. 50 minutes, then general and specialized discussion.

Where:

IMBIT, Nexus Lab, George-Köhler-Allee 201, 79110 Freiburg im Breisgau

More about the speaker and his research

Jean-Christophe Cassel

Host

Ulrich Egert