Neuroscience
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In the mammalian spinal cord, the ventrolateral funiculus (VLF) has been identified as critical to postural control and locomotor function, in part due to the reticulospinal pathways it contains. The primary purpose of this descriptive study was to investigate the distribution of neurons in the medulla labeled retrogradely from the VLF and the intermediate gray matter of specific lumbar and cervical spinal cord segments in the adult rat. We made discrete injections of Fluoro-Ruby (FR) into the intermediate gray matter at the cervical (C) 5/6, 7/8 or lumbar (L) 2 segmental levels followed by a single injection of Fluoro-Gold (FG) into the right VLF at T9. ⋯ These results describe a substantial population of ipsilateral and commissural medullary neurons that project to both cervical and thoracolumbar segments. Two different populations of commissural neurons are described, one with axons that cross the midline rostral to T9, and one with axons that cross the midline caudal to T9. These observations provide strong additional evidence for a pattern of reticulo- and vestibulospinal projections that include substantial numbers of commissural neurons and project to multiple cervical and thoracolumbar levels.
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Research indicates that pain negatively impacts attention; however, the extent of this impact and the mechanisms of the effect of pain on normal attentional processing remain unclear. This study 1) examined the impact of acute inflammatory pain on attentional processing, 2) examined the impact of morphine on attentional processing, and 3) determined if an analgesic dose of morphine would return attentional processing to normal levels. Male Sprague-Dawley rats were trained on the 5 choice serial reaction time task (5CSRTT), a test commonly used to assess the attentional mechanisms of rodents. ⋯ Likewise, a high dose of morphine (6 mg/kg) produced similar decrements in task performance. Of primary importance is that 3 mg/kg of morphine produced analgesia with only mild sedation, and performance in the 5CSRTT was improved with this dose. This is the first study to use an animal model of acute pain to demonstrate the negative impact of pain on attention, and provides a novel approach to examine the neural correlates that underlie the disruptive impact of pain on attention.
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Methamphetamine (MA) is a drug of abuse as well as a dopaminergic neurotoxin. We have previously demonstrated that pretreatment with bone morphogenetic protein 7 (BMP7) reduced 6-hydroxydopamine-mediated neurodegeneration in a rodent model of Parkinson's disease. In this study, we examined the neuroprotective effects of BMP7 against MA-mediated toxicity in dopaminergic neurons. ⋯ High doses of MA significantly suppressed beta-gal activity in striatum, suggesting that MA may inhibit BMP7 expression at the terminals of the nigrostriatal pathway. A similar effect was also found in CD1 mice in that high doses of MA suppressed BMP7 mRNA expression in nigra. In conclusion, our data indicate that MA can cause lesioning in the nigrostriatal dopaminergic terminals and that BMP7 is protective against MA-mediated neurotoxicity in central dopaminergic neurons.
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We have investigated effects of letrozole, an aromatase inhibitor, on spatial learning and memory, expression of neural cell adhesion molecules (NCAM) and catecholaminergic neurotransmitters in the hippocampus and cortex of female rats. In the intact model, adult Sprague-Dawley rats were divided into four groups (n=8). Control received saline alone. ⋯ Letrozole had differential effects on noradrenaline and dopamine content in the cortex. It appears that inhibition of estrogen synthesis in the brain may have beneficial effects on spatial memory. We suggest that structural changes such as NCAM expression and catecholaminergic neurotransmitters in the hippocampus and prefrontal cortex may be the neural basis for estrogen-dependent alterations in cognitive functions.
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N-methyl-d-aspartate receptors (NMDARs) are critical determinants of bidirectional synaptic plasticity, however, studies of NMDAR function have been based primarily on pharmacological and electrophysiological manipulations, and it is still debated whether there are subunit-selective forms of long-term potentiation (LTP) and long-term depression (LTD). Here we provide ultrastructural analyses of axospinous synapses in cornu ammonis field 1 of hippocampus (CA1) stratum radiatum of transgenic mice with mutations to two key underlying postsynaptic density (PSD) proteins, postsynaptic density protein 95 (PSD-95) and the alpha-isoform of calcium-calmodulin-dependent protein kinase II (alphaCaMKII). Distribution profiles of synaptic proteins in these mice reveal very different patterns of subunit-specific NMDAR localization, which may be related to the divergent phenotypes of the two mutants. ⋯ In an experiment of mutual exclusivity, neither PSD-95 nor alphaCaMKII localization was found to be affected by mutations to the corresponding PSD protein suggesting that they are functionally independent of the other in the regulation of NR2A- and NR2B-containing NMDARs preceding synaptic activity. Consequently, there may exist at least two distinct PSD-95 and alphaCaMKII-specific NMDAR complexes involved in mediating LTP and LTD through opposing signal transduction pathways in synapses of the hippocampus. The contrasting phenotypes of the PSD-95 and alphaCaMKII mutant mice further establish the prospect of an independent and, possibly, competing mechanism for the regulation of NMDAR-dependent bidirectional synaptic plasticity.