Neuroscience
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The change in synaptic inputs through primary afferent C- and A-fibers during postnatal development was examined in substantia gelatinosa neurons of a rat spinal cord slice with an attached L5 dorsal root by use of the blind whole-cell patch-clamp technique; the synaptic responses were compared between the slices obtained from immature (postnatal days 21-23) and mature (postnatal days 56-60) male rats. The mono- and/or polysynaptic afferent inputs were monitored by recording glutamatergic excitatory postsynaptic currents and potentials evoked by stimulating C- and A-fibers, the identification of which was based on the values of threshold stimulus intensity and of the conduction velocity of the fibers, determined by intracellular recordings from dorsal root ganglion neurons. Immature substantia gelatinosa neurons received synaptic inputs through Abeta-, Adelta- and C-afferents, with proportions of 51%, 46% and 36%, respectively. ⋯ In both immature and mature rats, repetitive stimulation of C-afferents did not elicit any slow responses, which are longer in duration than the monosynaptic excitatory postsynaptic currents, although C-fibers are known to contain not only excitatory amino acids, but also neuropeptides such as substance P, which is thought to be involved in the production of slow responses. These results indicate that both C- and Adelta-afferents innervating substantia gelatinosa neurons are reorganized following maturation, accompanied by a withdrawal or elimination of Abeta-fibers from the substantia gelatinosa, probably due to a competition among the fibers during development. In spite of the developmental increase in C-fiber inputs, mature as well as immature substantia gelatinosa neurons did not display any slow synaptic responses, which appear to be mediated by transmitters other than excitatory amino acids.
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Age-related changes in learning and memory are common in rodents. However, direct comparisons of the effects of aging on learning and memory in both males and females are lacking. The present study examined whether memory deteriorates with increasing age in C57BL/6NIA mice, and whether age-related changes in learning and memory are similar in both sexes. ⋯ Estrous cycling in females deteriorated significantly with increased age; all 25-month-old females had ceased cycling and 80% of 17-month-old females displayed either irregular or absent estrous cycling. This study is the first to directly compare age-related mnemonic decline in male and female mice. The results suggest that: (i) aged mice exhibit significant deficits in spatial and olfactory reference memory relative to young mice, whereas middle-aged mice exhibit only a moderate spatial memory deficit and; (ii) spatial reference memory decline begins at an earlier age in females than in males, a finding that may be related to the cessation of estrous cycling.
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Following cholinergic denervation of the hippocampus by medial septal lesions, an unusual neuronal reorganization occurs in which peripheral adrenergic fibers arising from superior cervical ganglia grow into the hippocampus (hippocampal sympathetic ingrowth). Recent studies suggest that a similar process, in which sympathetic noradrenergic axons invade the hippocampus, can occur in Alzheimer's disease patients. In the last few years, the occurrence of apoptotic cell death has been studied in Alzheimer's disease patients and in animal models of this disorder. ⋯ The cytosolic expression of bcl-x was increased in hippocampal sympathetic ingrowth compared to control and cholinergic denervation. The cytosolic activity of caspase-3 appeared to be significantly decreased in hippocampal sympathetic ingrowth and increased in cholinergic denervation groups compared to control and cholinergic denervation/hippocampal sympathetic ingrowth, respectively. From the present results, we suggest that cholinergic denervation may be responsible for pro-apoptotic responses, while hippocampal sympathetic ingrowth may protect neurons from apoptosis in rat dorsal hippocampus.
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The present study examined immunohistochemically the CNS distributions of a splice variant of the mu-opioid receptor, MOR-1D, in both rats and mice. In MOR-1D, exon 4 of MOR-1 is replaced by two additional exons that code for seven amino acids. Using rabbit antisera, we compared immunohistochemically the regional distribution of a C-terminal epitope of MOR-1D to that of a C-terminal epitope from MOR-1 and a C-terminal epitope from another splice variant, MOR-1C. ⋯ MOR-1D and MOR-1C are splice variants of the cloned mu-opioid receptor MOR-1. Although they differ only at the tip of the carboxy terminus, they show marked differences in their regional distributions, as determined immunohistochemically by epitopes in their unique carboxy termini. Since the splice variants are derived from the same gene, these differences in regional distribution imply region-specific messenger RNA processing.
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The serotonergic metacerebral giant cell (C1) of Helix pomatia was isolated with its bifurcate axon and plated in culture under five conditions: (i) with no target; (ii) with the appropriate target B2 near the stump of the bigger branch (CBC); (iii) with B2 near the stump of the smaller branch (CC); (iv) with a wrong target (C3) near the stump of the CBC branch and (v) with B2 and C3 positioned near the CBC and CC stump, respectively. The counting of anti-serotonin antibody-labelled varicosities of the C1 neuron showed that the presence of the appropriate target in either axonal domain both down-regulated the number of varicosities of the contralateral neuritic field, and increased their average size, whereas the wrong target induced an overall reduction of the number of C1 neuron varicosities, and inhibited the evoked transmitter release. The action potential-evoked calcium concentration increase in the neuritic terminals of the C1 neuron cultured alone, or in presence of the appropriate target, reached a value significantly higher than that reached in presence of the wrong target. These results provide evidence that the postsynaptic neuron regulates both morphological and functional development of presynaptic terminals.