Neocortex frontal

Recent research has indicated select abnormalities in the cholinergic system (Perry et al., 2001). Although previously unexamined neurochemically, there was an indication that the cholinergic system may be involved in autism, with abnormalities reported in neurons in the basal forebrain (Bauman Kemper, 1994). Perry et al. (2001) found extensive loss of high affinity nicotinic receptors from the neocortex (frontal and parietal), and from the cerebellum (Lee, et al., in preparation). Nicotinic receptors are implicated in attention, and also consciousness as many general anaesthetics block the receptor channel (Chapter 9). 

Textbooks on neuroscience often describe the location and function of hundreds of individual brain regions (see references above). However, for current purposes these will be kept to a minimum (Figure 2.1). Anatomically, the brain can be subdivided into the forebrain containing the telencephalon and diencephalon, the midbrain or mesencephalon and the hindbrain (metencephalon and myelencephalon). The telencephalon includes the left and right cerebral hemispheres encompassed by the cerebral cortex (neocortex). Cortex is a translation of the word bark and is so-called because its surface, made up of numerous sulci (grooves or invaginations) and gyri (raised areas), is on the outer surface of the brain like the bark of a tree. Each hemisphere is divided into four lobes, named from the front (rostral) to back (caudal) of the brain frontal, temporal, parietal and occipital. 

NeuN (Eriksson et al. 1998 Gould et al. 1999b, 2001 Kornack and Rakic 1999, 2001b Arvidsson et al. 2002 Parent et al. 2002) in an attempt to identify double-labeled cells whose size and morphology were similar to the surrounding NeuN+ neurons. We indeed found such cells, typically located in layers II-IV of the neocortex (Fig. 59) or lateral putamen in striatum (Fig. 60). Morphologically, BrdU+/NeuN+ cells (Fig. 59, 60 arrows) were similar in size and shape to adjacent BrdU /NeuN+ neurons (Fig. 59,60 arrowheads). Confocal analysis revealed that the NeuN+/BrdU+ constituted about 1% of the BrdU+ cells in either frontal neocortex or striatum (Table 10). 

Fig. 61A, B Immunophenotype of BrdU+/Musashil+ cells in frontal neocortex on postis-chemic day 44. A Two adjacent BrdU+/Musashil+ cells are triple-labeled for GFAP (arrows). B A BrdU+/Musashil+/GFAP cell is depicted in frames, while adjacent BrdU"/Musashil+/GFAP+ cells are depicted by arrowheads. The cell in frames is presented with 3D orthogonal projections in the bottom panel. Msil, Musashil. Scale bar= 10 pm...

In the neocortex, a main target of DA neurotransmission is the frontal cortex, where it could mediate effects of DA on psychiatric disorders, as shown by studies on antipsychotic drugs which all bind D2 receptors. 

In the neocortex, D2 receptor was detected with the highest density in layer V of frontal, parietal and occipital areas (Lidow et al., 1991). 

Similar to the D5 receptor, the D1B receptor is expressed in the neocortex, with highest expression in frontal, parietal and temporal areas of the rat cortex (Meador-Woodruff et al., 1994b Niznik et al., 2003). Moreover, similarly to Di mRNA, D5 mRNA is most abundant in discrete cortical layers (II, IV, VI) (Beischlag et al., 1995). Di and D5 mRNA are frequently coexpressed in pyramidal neurons, with predominant localization in the dendritic shaft of these cells (Bergson et al., 1995b). 

The typical changes seen in all subtypes of FTD are atrophy of the prefrontal and anterior temporal neocortex. The subtype determines the distribution of the pathology. In FTD there is prominent bilateral and usually symmetrical involvement of the frontal lobes. In PNFA, atrophy is asymmetric, involving chiefly the left frontotemporal lobes, concentrated in Broca s area. In SD, atrophy is typically bilateral and is most marked in the anterior temporal neocortex, with inferior and middle temporal gyri being predominantly affected (Snowden et al., 2002). 

Fig. 6. Regional brai n incorporation coefficient A of [ 1 - CJarachidonate, as percent contralateral valne, at 2 wk after a nnilateral ablation of the nucleus basalis in rats, with or without prior administration of arecoline. The gray background identifies regions with decreased acetylcholinesterase (AChE) activity. Lined bar s are means SEM. I, IV, V layers of neocortex Pr-F, prefrontal Fr, frontal Sm, sensorimotor M, motor Par, parietal Occ, occipital. Tern, temporal. (From Nariai et al., 1991b).

Indeed, Otxl expression is heterogeneous across the regions of the adult cortex, suggesting that it might also be involved in the forming of the cortical areas. Its expression in layer 5 is more prominent in the posterior and lateral cortex but absent in the frontal, insular, and orbital cortices, while in layer 6 it is more uniform throughout the neocortex (Frantz et al., 1994). 

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