Evidence for a role of GABA interneurones in the cortical modulation of midbrain 5-hydroxytryptamine neurones

Recent electrophysiological studies demonstrate that the ventral medial pre frontal cortex has a powerful inhibitory influence on 5-hydroxytryptamine ( 5-HT) neurones in the dorsal raphe nucleus. Here we utilised a combination of anatomical and electrophysiological methods to characterise the cellular substrate underlying this effect. Anterograde tracing (Phaseolus vulgaris leucoagglutinin) using electron mic roscopy demonstrated a pathway from the ventral medial prefrontal cortex th at makes neuronal contacts throughout the dorsal raphe nucleus. These conta cts were predominantly asymmetrical synapses adjoining GABA immunoreactive dendrites and spines. In vivo extracellular recordings were made in the dorsal raphe nucleus of t he anaesthetised rat from a subpopulation of non-5-HT neurones. These neuro nes were fast-firing, irregular and with short spike width, properties stro ngly reminiscent of immunochemically identified GABA interneurones. in othe r brain regions. Recordings of classical 5-HT neurones were also included. Electrical stimulation of the ventral medial prefrontal cortex elicited a r apid onset (16 ms latency), orthodromic excitation of the non-5-HT neurones (13/25 neurones). This stimulation also caused a pronounced inhibition of most 5-HT neurones tested, with a longer latency (30 ins), and this was par tially blocked by locally applied bicuculline. These data provide the first evidence that the ventral medial prefrontal. c ortex influences the activity of large numbers of raphe 5-HT neurones by ta rgeting a local network of GABA neurones. This circuitry predicts that phys iological and pathological changes in the ventral medial prefrontal cortex will impact on significant parts of the forebrain 5-HT system. (C) 2001 IBR O. Published by Elsevier Science Ltd. All rights reserved.