THE SEROTONERGIC INNERVATION OF THE CEREBRAL-CORTEX IN MAN AND ITS CHANGES IN FOCAL CORTICAL DYSPLASIA

We present the morphology and the laminar distribution of the serotoni n (5-hydroxytryptamine, 5-HT) innervation of the cerebral cortex of pa tients who underwent cortical resection for partial seizures, The limi ts of the resections were established by stereoelectroencephalography. The 5-HT innervation was mapped by using an antiserum anti-5-HT. Two patients had cryptogenic epilepsies and two others had seizures relate d to focal cortical dysplasia. 5-HT immunoreactive axons were morpholo gically heterogeneous and projected diffusely to the cerebral cortex w ith regional-specific densities, Two types of terminal axon were demon strated. Type I had large and spherical (intensely immunoreactive) var icosities and was distributed sparsely with a characteristic predomina nce in the molecular layer, Type II had fine and pleiomorphic varicosi ties (granular or fusiform) and was distributed through all cortical l ayers. The distribution of the 5-HT innervation varied according to th e different architectonic areas investigated. The granular cortical ar eas characterized by a highly developed layer IV (primary somatosensor y, primary visual and prefrontal cortices) had the highest density of 5-HT-ir fibers distributed from layer I to layer V. The agranular prim ary motor cortex had the lowest density with fibers preferentially see n in layers I, IIIa and V-VI. The orbital cortex with a poorly defined layer IV had an intermediate density with a laminar repartition predo minant in the supragranular layers. In patients with cryptogenic epile psies, the brain epileptogenic tissue was histologically normal as wel l as the serotonergic innervation. In contrast, in patients with focal cortical dysplasia, the dysplastic epileptogenic tissue was character ized by a serotonergic hyperinnervation. In agreement with previous da ta in primates, we give morphological evidence for two morphologically distinct serotonergic subsystems and for regional-specific densities in the human cerebral cortex. Moreover, we previously reported an alte red pattern of the catecholaminergic innervation in the same dysplasia areas. All these results provide evidence that this developmental epi leptogenic lesion involves several sets of neurons which may contribut e to epileptogenic activity.