The Journal of comparative neurology
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Muscarinic neurotransmission in the anterior basolateral amygdalar nucleus (BLa) mediated by the M1 receptor (M1R) is critical for memory consolidation. Although knowledge of the subcellular localization of M1R in the BLa would contribute to an understanding of cholinergic mechanisms involved in mnemonic function, there have been no ultrastructural studies of this receptor in the BLa. In the present investigation, immunocytochemistry at the electron microscopic level was used to determine which structures in the BLa express M1R. ⋯ About three-quarters of VAChT+ cholinergic terminals formed synapses; the main postsynaptic targets were M1R+ dendritic shafts and spines. In some cases M1R-ir was seen near the postsynaptic membrane of these processes, but in other cases it was found outside of the active zone of VAChT+ synapses. These findings suggest that M1R mechanisms in the BLa are complex, involving postsynaptic effects as well as regulating release of neurotransmitters from presynaptic terminals.
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The neurofilament light (NFL) subunit is considered as an obligate subunit polymer for neuronal intermediate filaments comprising the neurofilament (NF) triplet proteins. We examined cytoskeletal protein levels in the cerebral cortex of NFL knockout (KO) mice at postnatal day 4 (P4), 5 months, and 12 months of age compared with age-matched wild-type (WT) mice of a similar genetic background (C57BL/6). The absence of NFL protein resulted in a significant reduction of phosphorylated and dephosphorylated NFs (NF-P, NF-DP), the medium NF subunit (NFM), and the intermediate filament α-internexin (INT) at P4. ⋯ Neurons that lacked NF triplet proteins, such as calretinin-immunolabeled nonpyramidal cells, showed no alterations in density or cytoarchitectural distribution in NFL KO mice at 5 months relative to WT mice, although calretinin protein levels were decreased significantly after 12 months in NFL KO mice. These findings suggest that a lack of NFL protein alters the expression of cytoskeletal proteins and disrupts other NF subunits, causing intracellular aggregation but not gross structural changes in cortical neurons or cytoarchitecture. The data also indicate that changes in expression of other cytoskeletal proteins may compensate for decreased NFs.
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Prenatal exposure of the brain to environmental insult causes different neurological symptoms and behavioral outcomes depending on the time of exposure. To examine the cellular bases for these differences, we exposed rhesus macaque fetuses to x-rays during early gestation (embryonic day [E]30-E42), i.e., before the onset of corticogenesis, or in midgestation (E70-E81), when superficial cortical layers are generated. Animals were delivered at term (~E165), and the size and cellular composition of prefrontal association cortex (area 46) examined in adults using magnetic resonance imaging (MRI) and stereologic analysis. ⋯ A cell-sparse gap, observed within layer III, was not filled by the later-generated neurons destined for layer II, indicating that there is no subsequent replacement of the lost neurons. The distinct areal and laminar pathology consequent to temporally segregated irradiation is consistent with basic postulates of the radial unit hypothesis of cortical development. In addition, we show that an environmental disturbance inflicted in early gestation can induce subtle cytoarchitectonic alterations without loss of neurons, such as those observed in schizophrenia, whereas midgestational exposure causes selective elimination of neurons and cortical thinning as observed in some forms of mental retardation and fetal alcohol syndrome.
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Corticothalamic (CT) feedback outnumbers thalamocortical projections and regulates sensory information processing at the level of the thalamus. It is well established that EphA7, a member of EphA receptor family, is involved in the topographic mapping of CT projections. The aim of the present study was to dissect the precise impact of EphA7 on each step of CT growth. ⋯ Large-scale overproduction and elimination of exuberant widespread axonal branches outside the target zone was not observed. Each developmental event was coordinated by spatially and temporally different responsiveness of CT axons to the ephrin-A gradient in thalamic nuclei, as well as by the matching levels of EphA7 in CT axons and ephrin-As in thalamic nuclei. These results support the concept that the topographic connections between the maps in the cerebral cortex and corresponding thalamic nuclei are genetically prespecified to a large extent, and established by precise spatiotemporal molecular mechanisms that involve the Eph family of genes.
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Porcine lumbosacral dorsal root ganglion (DRG) neurons were neurochemically characterized by using six neuronal markers: calcitonin gene-related peptide (CGRP), substance P (SP), neuronal nitric oxide synthase (nNOS), neurofilament 200kDa (NF200), transient receptor potential vanilloid 1 (TRPV1), and isolectin B4 (IB4) from Griffonia simplicifolia. In addition, the phenotype and cross-sectional area of DRG neurons innervating the urinary bladder trigone (UBT) were evaluated by coupling retrograde tracer technique and immunohistochemistry. Lumbar and sacral DRG neuronal subpopulations were immunoreactive (IR) for CGRP (30 ± 3% and 29 ± 3%, respectively), SP (26 ± 8% and 27 ± 12%, respectively), nNOS (21 ± 4% and 26 ± 7%, respectively), NF200 (75 ± 14% and 81 ± 7%, respectively), and TRPV1 (48 ± 13% and 43 ± 6%, respectively), and labeled for IB4 (56 ± 6% and 43 ± 10%, respectively). ⋯ Lumbar and sacral UBT sensory neurons also showed different IB4 labeling (67 ± 19% and 48 ± 16, respectively). Taken together, these data indicate that the lumbar and sacral pathways probably play different roles in sensory transmission from the UBT. The findings related to cell size also reinforced this hypothesis, because lumbar UBT sensory neurons were significantly larger than sacral ones (1,112 ± 624 μm(2) vs. 716 ± 421 μm(2) ).