Biology session

Subcortical monoaminergic pathways, like that originating from the serotonergic median raphe region (MRR), are fundamental for the modulation of forebrain neuronal networks. However, our workgroup showed recently that, beyond this serotonergic modulation, the vesicular glutamate transporter type 3 (vGluT3)-containing cells of the MRR can establish fast glutamatergic excitatory synapses on hippocampal GABAergic interneurons. We examined, whether this type of glutamatergic neurotransmission is typical in the forebrain connections of the MRR in the mouse brain.

First, using design-based stereological methods and fluorescent immunohistochemistry together with confocal microscopy, we labelled the serotonergic and/or vGluT3 positive cells of the MRR and we found that about two-thirds of the neurons are vGluT3 positive glutamatergic cells. Then, using retrograde tracing, we showed that about 80, 60 and 70% of the MRR cells projecting to the hippocampus, medial septum and medial prefrontal cortex are glutamatergic, respectively. Finally, using double retrograde tracing, we showed that there are several neurons in the MRR that innervate both the hippocampus and the medial prefrontal cortex simultaneously and about 90% of them are glutamatergic. In addition, about 80% of the cells projecting both to the medial septum and the medial prefrontal cortex are also glutamatergic.

Our results show that although the serotonin content of MRR cells is indeed typical, nevertheless, besides many of the cells being doubled positive, the vast majority of these neurons are glutamatergic projecting cells. Furthermore, because these cells can innervate more brain areas simultaneously, the MRR can precisely synchronize these brain areas. While the MRR was previously thought to be a tonic modulatory serotonergic nucleus, these observations put this nucleus into a new perspective and can help us to understand its real functions.