The Subcortical-Allocortical- Neocortical continuum for the Emergence and Morphological Heterogeneity of Pyramidal Neurons in the Human Brain.

Human cortical and subcortical areas integrate emotion, memory, and cognition when interpreting various environmental stimuli for the elaboration of complex, evolved social behaviors. Pyramidal neurons occur in developed phylogenetic areas advancing along with the allocortex to represent 70-85% of the neocortical gray matter. Here, we illustrate and discuss morphological features of heterogeneous spiny pyramidal neurons emerging from specific amygdaloid nuclei, in CA3 and CA1 hippocampal regions, and in neocortical layers II/III and V of the anterolateral temporal lobe in humans. Three-dimensional images of Golgi-impregnated neurons were obtained using an algorithm for the visualization of the cell body, dendritic length, branching pattern, and pleomorphic dendritic spines, which are specialized plastic postsynaptic units for most excitatory inputs. We demonstrate the emergence and development of human pyramidal neurons in the cortical and basomedial (but not the medial, MeA) nuclei of the amygdala with cells showing a triangular cell body shape, basal branched dendrites, and a short apical shaft with proximal ramifications as "pyramidal-like" neurons. Basomedial neurons also have a long and distally ramified apical dendrite not oriented to the pial surface. These neurons are at the beginning of the allocortex and the limbic lobe. "Pyramidal-like" to "classic" pyramidal neurons with laminar organization advance from the CA3 to the CA1 hippocampal regions. These cells have basal and apical dendrites with specific receptive synaptic domains and several spines. Neocortical pyramidal neurons in layers II/III and V display heterogeneous dendritic branching patterns adapted to the space available and the afferent inputs of each brain area. Dendritic spines vary in their distribution, density, shapes, and sizes (classified as stubby/wide, thin, mushroom-like, ramified, transitional forms, "atypical" or complex forms, such as thorny excrescences in the MeA and CA3 hippocampal region). Spines were found isolated or intermingled, with evident particularities (e.g., an extraordinary density in long, deep CA1 pyramidal neurons), and some showing a spinule. We describe spiny pyramidal neurons considerably improving the connectional and processing complexity of the brain circuits. On the other hand, these cells have some vulnerabilities, as found in neurodegenerative Alzheimer's disease and in temporal lobe epilepsy.

Neuronal types of the human cortical amygdaloid nucleus.

The human cortical amygdaloid nucleus (CoA) receives exteroceptive sensory stimuli, modulates the functions coded by the intrinsic amygdaloid circuit, and constitutes the beginning of the limbic lobe continuum with direct and indirect connections toward subcortical, allocortical, and higher order neocortical areas. To provide basic data on the human CoA, we characterized and classified the neurons using the thionin and the "single-section" Golgi method adapted for postmortem brain tissue and light microscopy. We found 10 different types of neurons named according to the morphological features of the cell body, dendritic branches, and spine distribution. Most cells are multipolar spiny neurons with two or more primary dendrites, including pyramidal-like ones. Three-dimensional reconstructions evidenced the types and diversity of the dendritic spines in each neuron. The unlike density of spines along dendritic branches, from proximal to distal ones, indicate that the synaptic processing and plasticity can be different in each CoA neuron. Our study provides novel data on the neuronal composition of the human CoA indicating that the variety of cells in this region can have phylogenetic, ontogenetic, morphological, and likely functional implications for the integrated human brain function. This can reflect both a more complex subcortical synaptic processing of sensory and emotional information and an adaptation for species-specific social behavior display.

Structure and diversity of human dendritic spines evidenced by a new three-dimensional reconstruction procedure for Golgi staining and light microscopy.

BACKGROUND: Different approaches aim to unravel detailed morphological features of neural cells. Dendritic spines are multifunctional units that reflect cellular connectivity, synaptic strength and plasticity. NEW METHOD: A novel three-dimensional (3D) reconstruction procedure is introduced for visualization of dendritic spines from human postmortem brain tissue using brightfield microscopy. The segmentation model was based on thresholding the intensity values of the dendritic spine image along 'z' stacks. We used median filtering and removed false positives. Fine adjustments during image processing confirmed that the reconstructed image of the spines corresponded to the actual original data. RESULTS: Examples are shown for the cortical amygdaloid nucleus and the CA3 hippocampal area. Structure of spine heads and necks was evaluated at different angles. Our 3D reconstruction images display dendritic spines either isolated or in clusters, in a continuum of shapes and sizes, from simple to more elaborated forms, including the presence of spinule and complex 'thorny excrescences'. COMPARISON WITH EXISTING METHODS: The procedure has the advantages already described for the adapted "single-section" Golgi method, since it provides suitable results using human brains fixed in formalin for long time, is relatively easy, requires minimal equipment, and uses an algorithm for 3D reconstruction that provides high quality images and more precise morphological data. CONCLUSION: The procedure described here allows the reliable visualization and study of human dendritic spines with broad applications for normal controls and pathological studies.