Hippocampal pyramidal cells of the CA1 region are not a major target of the thalamic nucleus reuniens

The prefrontal-hippocampal-entorhinal system is perhaps the most widely-studied circuit in cognitive and systems neuroscience, due to its role in supporting cognitive functions such as working memory and decision-making. Disrupted communication within this circuit is a key feature of disorders such as schizophrenia and dementia. Nucleus reuniens (NRe) is a midline thalamic nucleus that sits at the nexus of this circuit, linking these regions together. As there are no direct projections from prefrontal cortex to hippocampus (HPC), the accepted model is that the NRe mediates prefrontal drive of hippocampal activity, although these connections are poorly defined at the cellular and synaptic level. Using ex vivo optogenetics and electrophysiology in both mice and rats, alongside monosynaptic circuit-tracing, we sought to test the mechanisms through which NRe could drive hippocampal activity. Unexpectedly, we found no evidence that pyramidal cells in CA1 receive input from NRe, with midline thalamic input to HPC proper appearing selective for GABAergic interneurons. In other regions targeted by NRe, we found that pyramidal cells in prosubiculum and subiculum received synaptic inputs from NRe that were at least an order of magnitude weaker than those in prefrontal or entorhinal cortices. We conclude that, contrary to widely-held assumptions in the field, hippocampal pyramidal cells are not a major target of NRe.