ORIGIN OF THE NORADRENALINE INNERVATION OF THE MIDLINE, MEDIODORSAL, VENTRAL ANTERIOR, AND LATERAL POSTERIOR THALAMIC NUCLEI

Noradrenaline (NA) modulates brain circuits partly through the thalamus, where its innervation is heterogeneous in primates and particularly dense in midline nuclei. Here, we investigated the origin of NA innervation to the midline, mediodorsal (MD), ventral anterior (VA), and lateral posterior (LP) thalamic nuclei.
Retrograde tracer injections (CtB-Au) in these nuclei were combined with immunohistochemistry for dopamine β-hydroxylase (DβH) to identify NA neurons in the brainstem.
The origin of NA innervation was bilateral. Midline thalamic nuclei received the most prominent NA input: approximately 20% of all brainstem NA neurons projected to midline nuclei. Most of these neurons were located in the locus coeruleus complex (LC; A6, subcoeruleus, and A4), although substantial contributions from A7, A5, A1, and A2 groups were also observed. MD received a smaller but still substantial NA projection, accounting for about 6% of total NA neurons, originating predominantly from the LC, with minor contributions from other NA nuclei. VA and LP nuclei showed an even more limited NA innervation, arising mainly from the LC.
Overall, our results reveal a gradient in the number and heterogeneity of brainstem NA neurons innervating the thalamus, with midline nuclei receiving the broader and more heterogeneous input, followed by MD, and then VA and LP nuclei. This organization suggests a prominent noradrenergic modulation, mostly of limbic and arousal-related thalamic circuits.
Funded by the Chair in Neuroscience UAM-Fundación Tatiana and the Spanish Ministry of Science, Innovation, and Universities (MICIU/AEI/10.13039/501100011033) under project PID2024-161329NA-I00.