Search

Ts65Dn mice are partially trisomic for the distal region of MMU16, which is homologous with the obligate segment of HSA21 triplicated in Down syndrome (DS). Ts65Dn mice are impaired in learning tasks that require an intact hippocampus. In order to investigate the neural basis of these deficits in this mouse model of Down syndrome, quantitative light and electron microscopy were used to compare the volume densities of neurons and synapses in the hippocampus of adult Ts65Dn (n=4) and diploid mice (n=4). Neuron density was significantly lower in the CA1 of Ts65Dn compared to diploid mice (p<0.01). Total synapse density was significantly lower in the dentate gyrus (DG; p<0.001), CA3 (p<0.05) and CA1 (p<0.001) of Ts65Dn compared to diploid mice. The synapse-to-neuron ratio was significantly lower in the DG (p<0.001), CA3 (p<0.01) and CA1 (p<0.001) of Ts65Dn compared to diploid mice. When the data were broken down by synapse type, asymmetric synapse density was found to be significantly lower in the DG (p<0.001), CA3 (p<0.05) and CA1 (p<0.001) of Ts65Dn compared to diploid mice, while such a difference in symmetric synapse density was only present in the DG (p<0.01). The asymmetric synapse-to-neuron ratio was significantly lower in the DG (p<0.001), CA3 (p<0.01) and CA1 (p<0.001) of Ts65Dn compared to diploid mice, but there were no such significant differences in symmetric synapse-to-neuron ratios. These results suggest that impaired synaptic connectivity in the hippocampus of Ts65Dn mice underlies, at least in part, their cognitive impairment.

In birds, as in mammals, corticotropin-releasing factor (CRF) is present in a number of extrahypothalamic brain regions, indicating that CRF may play a role in physiological and behavioral responses other than the control of adrenocorticotropin hormone release by the pituitary. To provide a foundation for investigation of the roles of CRF in the control of avian behavior, the distribution of CRF immunoreactivity was determined throughout the central nervous system of the domestic chicken (Gallus domesticus) and Japanese quail (Coturnix japonica). The distribution of CRF-immunoreactive (-ir) perikarya and fibers in the chicken and quail brain was found to be more extensive than previously reported, notably in the telencephalon. Numerous CRF-ir perikarya and fibers were present in the hyperstriatum, hippocampus, neostriatum, lobus parolfactorius, and archistriatum, as well as in the nucleus taeniae, nucleus accumbens, and bed nucleus of the stria terminalis, which exhibited the strongest immunolabeling in the telencephalon. The presence of dense populations of CRF-ir perikarya in the medial lobus parolfactorius, nucleus of the stria terminalis, and paleostriatum ventrale, apparently giving rise to CRF-ir projections to the mesencephalic reticular formation, the parabrachial/pericerulear region, and the dorsal vagal complex, suggests that these telencephalic areas may constitute part of the avian "central extended amygdala." These results have important implications for understanding the role of extrahypothalamic CRF systems in emotional responses in birds., (Copyright 2004 Wiley-Liss, Inc.)

The intrinsic neuronal organisation in the nucleus of the basal optic root of chickens was investigated. The divergent connections with various areas and the functional complexity of the nucleus require a complex intrinsic structural arrangement. Therefore, an analysis of Golgi impregnated material, ultrastructure, GABA-immunocytochemistry and biotinylated dextran-amine anterograde tracer analysis of the nucleus was carried out. In the Golgi analysis, a characteristic dendritic ramification pattern of two types of putative projection neurons was observed. These neurons form dendritic nests with their overlapping dendritic terminal sections, that develop synaptic fields with the optic fibre terminals. These synaptic fields were confirmed by electron microscopy. GABA-immunopositive terminals synapse with distinct loci of the dendritic trees of projection neurons; they may therefore play an important role in the inhibitory-modulatory system of the nucleus of the basal optic root. The GABA-immunopositive terminals derive from small and/or elongated local circuit neurons which receive retinal afferents, and from myelinated fibres afferents to the nucleus of unknown origin.

Three types of local circuit neurons have recently been reported in the homing pigeon hippocampus. The principal type appears to be constituted by the medium-sized angular or ovoid local circuit neurons that occur in all layers of the hippocampus. The current Golgi study has revealed that these neurons can be classified according to their axonal arborisation extension: (1) in all directions, (2) principally medio-laterally, or (3) dorso-ventrally. The local circuit neurons with dorso-ventral axon arborisation are present only in the subpyramidal layer. Serial sections of a Golgi-impregnated medium-sized, multiangular local circuit neuron in the pyramidal layer and a small, ovoid neuron in the suprapyramidal layer were investigated in the electron microscope. Some of these sections were processed for GABA immunogold cytochemistry. The soma and large dendrites of both neurons displayed GABA immunogold labelling. On the soma of medium-sized local circuit neuron there were numerous terminals; on the soma of the small one relatively fewer terminals were observed. The terminals contained round and/or flat synaptic vesicles. The long axonal branches of the neurons exhibited varicosities containing flattened or pleomorphic vesicles. Axo-dendritic, axo-somatic and a few axo-axonic synapses were observed. The large dense axon arborisation field of medium-sized local circuit neurons is properly situated to modulate intrinsic hippocampal activity and that of the small local circuit neurons is well situated to modulate the hippocampal input in the suprapyramidal layer.

Investigation of the chick archistriatum revealed that it was not possible to distinguish distinct sub-regions on the basis of their Golgi architecture, despite the fact that the pigeon archistriatum has been suggested to comprise "amygdaloid" and "sensorimotor" divisions. Nine sub-types of projection neuron and four of local circuit neuron were identified in the chick archistriatum. Projection neurons were generally larger with thicker dendrites than those in other regions of the chick telencephalon. A greater proportion of these projection neurons also had highly densely spiny dendrites. These findings suggest that archistriatal neurons receive a large, possibly complex afferentation and project considerable distances. Large and medium-sized local circuit neurons with varicose axon branches and relatively large neurogliaform cells were characteristic of the archistriatum. All types of archistriatal neuron were identified in both 28 and one day old chicks. However, presumptive highly densely spiny projection neurons appeared relatively immature in the one day old chick archistriatum.

Pyramidal neuron density was determined at autopsy in the brains of 12 neurologically normal patients (age range 6-87 years) and 18 patients with histopathologically confirmed Alzheimer's disease (AD; age range 62-89 years). Paraffin wax sections were cut at the level of the central part of the cornu ammonis and stained with cresyl fast violet. Pyramidal neuron density was determined in the stratum pyramidale of the presubiculum, subiculum, prosubiculum and CA1-4. The width of the stratum pyramidale in these areas was also determined. There was no significant effect of age on pyramidal neuron density in any of the fields of the hippocampal formation. However, there was a significant decrease in pyramidal neuron density in the subiculum (44%), prosubiculum (28%) and CA1 (41%) of AD brains compared to controls. There was no significant effect of AD on pyramidal neuron density in the presubiculum, CA2 and CA3, but in CA4 it increased (23%) significantly. Pyramidal band width decreased significantly with age in the presubiculum but there was no effect of age on any other region of the hippocampal formation investigated. The width of the stratum pyramidale was significantly lower in the presubiculum (19%), subiculum (30%) and CA3 (17%) of AD compared with control brains. These data suggest that a reduction in pyramidal neuron density within the hippocampal formation does not occur in the absence of underlying pathology. In AD, pyramidal neuron loss predominantly occurs from that sector of the hippocampal formation which comprises the subiculum, prosubiculum and CA1.

Neuronal numbers in the neonatal rat superior cervical ganglion were estimated from counts made on paraffin wax sections stained with cresyl violet. The raw data were separately processed in accordance with the correction procedures of Abercrombie (1946) and of Hendry (1976). The results do not support the view that there is histogenic neuronal loss during the first 30 days post-partum. Figures corrected by the Abercrombie method indicated that the neuronal population is held stable throughout the first month of neonatal life at a level of about 35000 neurons. On the other hand, when the data was corrected by Hendry's method, the population appears to increase from less than 20000 to about 45000 neurons in the first week, and is then held at that level until the end of the study period. Moreover, histochemical studies using the acid-phosphatase reaction have previously indicated that there is little or no cell degeneration during this period.