Modulation of the Activity of Pyramidal Neurons in Rat Prefrontal Cortex by Raphe Stimulation In Vivo: Involvement of Serotonin and GABA

Abstract

Serotonin is involved in psychiatric disorders exhibiting abnormal prefrontal cortex (PFC) function (e.g. major depression, schizophrenia). We examined the effect of the stimulation of the dorsal and median raphe nuclei (DR and MnR, respectively) on the activity of PFC neurons. Electrical stimulation of DR/MnR inhibited 66% (115/173) of pyramidal neurons in the medial PFC (mPFC). The rest of the cases exhibited orthodromic excitations, either pure (13%) or preceded by short-latency inhibitions (20%). Excited neurons had a lower pre-stimulus firing rate than those inhibited. Excitations evoked by MnR stimulation had a shorter latency than those evoked by DR stimulation. WAY-100635 [a 5-hydroxytryptamine1A (5-HT1A) antagonist] and the selective gamma aminobutyric acidA (GABAA) antagonist picrotoxinin partially antagonized DR/MnR-evoked inhibitions, suggesting the involvement of 5-HT1A- and GABAA-mediated components. The presence of a direct DR/MnR-mPFC GABAergic component is suggested by the short latency of evoked inhibitions (9 +/- 1 ms), faster than those evoked in the secondary motor area (20 +/- 3 ms), and that of antidromic spikes evoked by DR/MnR stimulation in mPFC pyramidal neurons (15 +/- 1 ms). Stimulation of the DR/MnR with paired pulses enhanced the duration of inhibitions and turned some excitations into inhibitions. Thus, the DR/MnR control the activity of mPFC pyramidal neurons in vivo in a complex manner, involving 5-HT-mediated excitations and GABA- and 5-HT-mediated inhibitions.

Selective anterograde tracing of nonserotonergic projections from dorsal raphe nucleus to the basal forebrain and extended amygdala

“…It is entirely possible that larger BDA injections would have produced labeling in the neocortex, as well as in other brain regions in which little or no anterograde transport was detected. This conclusion seems likely, given that there is both neurochemical (Jankowski and Sesack, 2002) and electrophysiological (Puig et al, 2005) evidence that the DRN sends a GABAergic projection to medial prefrontal cortex. After injection of BDA into the DRN of animals pretreated with 5,7-DHT, anterograde labeling in the lateral septum (LS) was found primarily within a distinctive band that followed the border of the dorsal and intermediate subdivisions of the nucleus (see Figs.…”

Role of cortical spreading depression in the pathophysiology of migraine

“…Recently, we have also demonstrated that the brain serotonergic system, which is known to modulate the excitability of cortical neurons through activation of several receptor subtypes, in particular, 5-HT1A, 5-HT2A, and 5-HT3 receptors [47][48][49] , contributes to the propagation of cortical SD. Pyramidal neurons in the cerebral cortex express 5-HT1A and 5-HT2A receptors, which exert opposing effects on the excitability and firing activity of pyramidal neurons [47,49] .…”

“…The activation of the excitatory receptors 5-HT2A and 5-HT3 in GABAergic interneurons directly excites GABAergic interneurons, and indirectly inhibits the fi ring of pyramidal neurons in the cortex and hippocampus [51,52] . Although the activation of 5-HT2A receptors in pyramidal neurons results in the activation of neurons, a preferential inhibitory action of 5-HT has been reported in vivo [48] . Such a preferential inhibitory action of 5-HT on cortical neurons could be explained by the different binding affinities of 5-HT for 5-HT1A and 5-HT2 receptors.…”

“…Moreover, several studies have reported that the spread of SD stops where white matter [45,46] . Consistent with these observations, we also demonstrated that the velocity of cortical SD gradually decreases from the dorsal to the ventral cortical areas of the insular cortex, in which the volume distribution of astrocyte is known to gradually increase.Recently, we have also demonstrated that the brain serotonergic system, which is known to modulate the excitability of cortical neurons through activation of several receptor subtypes, in particular, 5-HT1A, 5-HT2A, and 5-HT3 receptors [47][48][49] , contributes to the propagation of cortical SD. Pyramidal neurons in the cerebral cortex express 5-HT1A and 5-HT2A receptors, which exert opposing effects on the excitability and firing activity of pyramidal neurons [47,49] .…”

“…Pyramidal neurons in the cerebral cortex express 5-HT1A and 5-HT2A receptors, which exert opposing effects on the excitability and firing activity of pyramidal neurons [47,49] . Activation of 5-HT1A receptors hyperpolarizes, whereas activation of 5-HT2A receptors depolarizes pyramidal neurons [47][48][49] . On the other hand, 5-HT2A receptors are expressed in large and 5-HT3 receptors in small GABAergic interneurons [50] .…”