An electrophysiological and neuroanatomical study of the medial prefrontal cortical projection to the midbrain raphe nuclei in the rat
Section snippets
Animals and surgical method
Male Sprague–Dawley rats (265–285 g, Harlan Olac, Bicester, U.K.) were anaesthetized with chloral hydrate (450 mg/kg, i.p.) and mounted in a stereotaxic frame (Kopf) with the incisor bar set at −3.3 mm. The skull was exposed and craniotomy was performed on the midline, above the region of the DRN. A lateral tail vein was cannulated for administration of drugs and additional doses of anaesthetic. Body temperature of the animals was maintained at 36°C throughout the experiment by means of a
Retrograde labelling
Both WGA–HRP and CTB–HRP injections into the DRN resulted in a bilateral labelling of neurons in the mPFC (Fig. 1).
Iontophoretic application of WGA–HRP labelled two to six mPFC neurons bilaterally. These neurons extended from the superficial to the deepest layers (2 to 6b) of the infralimbic and dorsal peduncular cortices (Fig. 1b). WGA–HRP staining was confined to the perikaryon and the proximal dendrites of small to medium sized cells (12–35 μm) with bitufted or pyramidal morphologies.
Large
Discussion
The present results provide the first electrophysiological evidence for a powerful functional connection between the mPFC and 5-HT neurons in the mesencephalic raphe nuclei. Specifically we found that, in anaesthetized rats, electrical stimulation of the ventral mPFC caused a clear-cut post-stimulus inhibition of the vast majority of 5-HT neurons in the DRN and MRN that we tested. Additionally, in a small proportion of neurons the inhibition was preceded by an orthodromic activation. These
Functional implications of the medial prefrontal cortex–raphe projection
The present data suggest that the majority of 5-HT neurons in the midbrain raphe nuclei are strongly influenced by the ventral mPFC. In terms of brain 5-HT function, this input from the ventral mPFC may be significant in two ways.
Firstly, it provides the raphe 5-HT system with a direct input from what is recognized to be a key brain region within the corticolimbic system which is critically involved in emotional and cognitive function. Previously, the main route of limbic input to the raphe
Acknowledgements
This work was supported by the Medical Research Council (U.K.) and OTKA F 012738 (Hungary). A. D. Székely was a recipient of a Wellcome Travel Grant.
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Present Address: Neuropsychopharmacology Laboratory, Department of Psychology, University of Wales, Swansea, SA2 8PP, U.K.