Over the past few years, I worked with Sian Duss, a very skilled and talented PhD student in the lab of Johannes Bohacek, to dissect the role of noradrenaline release in the hippocampus. I’m very excited that the manuscript describing this work is now online as a preprint: Locus coeruleus noradrenaline elicits response profiles distinct from natural arousal in hippocampal neurons and astrocytes.

We used two-photon imaging of interneurons, astrocytes, and pyramidal cells in head-fixed mice, while optogenetically stimulating the primary source of noradrenaline, the locus coeruleus (LC). In addition, we used fiber photometry to calibrate our LC stimulation protocol and to compare optogenetically evoked noradrenaline release with that observed during behavioral paradigms.

For the main findings, please check out the manuscript itself. In this blog post, I’d like to highlight a few results that I personally find fascinating but that are less central in the paper.

1. Astrocytes are much more sensitive to noradrenaline than neurons

Based on our two-photon calcium imaging data, pyramidal neurons and interneurons show little or no response to weaker LC stimulation and respond robustly only to strong stimulation. Astrocytes, in contrast, are highly sensitive and respond even to the lowest detectable increases in LC activity. This positions astrocytes ideally to mediate noradrenergic effects in hippocampal circuits. I find it great to have this very direct comparison across all three cell types – pyramidal cells, interneurons, and astrocytes – using the same experimental approach for each cell type.

2. Interneurons responsive to noradrenaline are located close to the stratum radiatum

Previous studies have already described that specific functionally defined interneurons are located in specific laminae or sub-laminae of hippocampus (e.g., Geiller et al., 2020). Here, we found that interneurons responding to noradrenaline release upon optogenetic LC stimulation are preferentially located near the pyramidal cell layer, close to the stratum radiatum.

3. Not all astrocytes are equal

We found that some astrocytes are much more sensitive than others when responding to locus coeruleus activation. These differences were consistent across repeated stimulations and across days. This adds evidence, from a functional perspective, that astrocytes are not a homogeneous population, even within the same hippocampal region.

For many more details on the cellular responses to locus coeruleus stimulation, and how these compare to response profiles during natural arousal, check out the preprint. Happy to hear thoughts or questions about the work!