Abstract
Proper development of the medial prefrontal cortex (mPFC), crucial for correct cognitive functioning, requires projections from, among others, the serotonergic (5-HT) and catecholaminergic systems, but it is unclear how these systems influence each other during development. Here, we describe the parallel development of the 5-HT and catecholaminergic prefrontal projection systems in rat and demonstrate a close engagement of both systems in the proximity of Cajal-Retzius cells. We further show that in the absence of the 5-HT transporter (5-HTT), not only the developing 5-HT but also the catecholaminergic system, including their projections towards the mPFC, are affected. In addition, the layer identity of the mPFC neurons and reelin-positive interneuron number and integration are altered in the absence of the 5-HTT. Together, our data demonstrate a functional interplay between the developing mPFC 5-HT and catecholaminergic systems, and call for a holistic approach in studying neurotransmitter systems-specific developmental consequences for adult behavior, to eventually allow the design of better treatment strategies for neuropsychiatric disorders.
Highlights
Proper functioning of neural systems and correct targeting of their often long projections to distant targets is crucial for cognitive performance
When we took a closer look at the origin of both ascending neural systems, the DA midbrain and the 5-HT DR and MnR at the coronal level, we were able to observe a close contiguity between the tyrosine hydroxylase (TH)+ and 5-HT+ axons (Fig. 1e–t)
We further demonstrate that within the medial prefrontal cortex (PFC) (mPFC), the TH and 5-HT fibers are in close proximity to reelin-containing CR cells, and are different in number when 5-HT transporter (5-HTT) is lacking
Summary
Proper functioning of neural systems and correct targeting of their often long projections to distant targets is crucial for cognitive performance. An important distant target of many neurotransmitter systems is the prefrontal cortex (PFC). The PFC is considered critical for executive and higher cognitive functioning [1,2,3].
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