Neuroscience
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Nitric oxide produced by neuronal nitric oxide synthase (nNOS) in the spinal cord is required for development of hyperalgesia in inflammatory and neuropathic pain states. nNOS is expressed by some dorsal horn neurons, and an early study that used a histochemical method to identify these cells suggested that they were mainly inhibitory interneurons. We have carried out a quantitative analysis of nNOS-immunoreactivity in laminae I-III of the rat dorsal horn, to determine the proportion of inhibitory and excitatory neurons and axonal boutons that express the protein. nNOS was present in ∼5% of neurons in laminae I and III, and 18% of those in lamina II. Although most cells with strong nNOS immunostaining were GABA-immunoreactive, two-thirds of the nNOS-positive cells in lamina II and half of those in lamina III were not GABAergic, and some of these expressed protein kinase Cγ (PKCγ). ⋯ However, it was only found in 2-4% of the VGAT boutons that were presynaptic to PKCγ-expressing interneurons in this region. These results indicate that nNOS is more widely expressed than previously thought, being present in both inhibitory and excitatory neurons. They provide further evidence that axons of neurochemically defined populations of inhibitory interneuron are selective in their post-synaptic targets.
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Agmatine, the decarboxylated metabolite of l-arginine, is considered to be a novel putative neurotransmitter. Recent studies have demonstrated that endogenous agmatine may directly participate in the processes of spatial learning and memory. Agmatine-immunoreactivity has been observed within synaptic terminals of asymmetric excitatory synapses in the hippocampal CA1 stratum radiatum (SR), suggesting that agmatine may be colocalized with glutamate. ⋯ Alterations in colocalized agmatine and glutamate levels in the SR synaptic terminals, following 4 days Morris water maze training, were also investigated. Compared with swim only control rats, water maze-trained rats had statistically significant increases in both agmatine (78%; P<0.01) and glutamate (41%; P<0.05) levels within SR terminals synapsing onto CA1 dendrites. These findings provide the first evidence that agmatine and glutamate are colocalized in synaptic terminals in the hippocampal CA1 region, and may co-participate in spatial learning and memory processing.
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Functional studies indicate that the dopamine D5 receptor is involved in synaptic transmission in the hippocampus. However, previous anatomical studies have detected D5 receptor labelling primarily on the soma and main dendrites of CA1 pyramidal cells and on dendritic spines in monkey but not in rats. ⋯ Hence, dopamine could have effects on spines as well as on somas and dendrites. The labelling density was similar on spines in stratum oriens and stratum radiatum, but the presence of labelling varied between the spines within each stratum, indicating that the effect of dopamine could be diverse between different spines.
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Experimentally naive rats show variance in their locomotor reactivity to novelty, some displaying higher (HR) while others displaying lower (LR) reactivity, associated with vulnerability to stress. We employed a chronic variable physical stress regimen incorporating intermittent and random exposures of physical stressors or control handling during the peripubertal-juvenile period to assess interactions between stress and the LRHR phenotype in depressive- and anxiety-like behaviors on the forced swim and social interaction tests, respectively. A decrease in immobility in the forced swim test along with a decrease in social contact in the social interaction test were observed in the juvenile HRs, coupled with increases in brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus and in the basolateral amygdala with chronic variable physical stress. ⋯ In contrast, chronic variable physical stress led to decreased H4 acetylation at the P4 promoter, associated with decreased SP-MF volume in the LR rats. These findings show dissociation in depressive- and anxiety-like behaviors following chronic variable physical stress in the juvenile HR animals that may be mediated by increased levels of BDNF in the hippocampus and in the amygdala, respectively. Moreover, chronic variable physical stress during the peripubertal-juvenile period results in opposite effects in depressive-like behavior in the LRHR rats by way of inducing differential epigenetic regulation of the hippocampal BDNF gene that, in turn, may mediate mossy fibre sprouting.
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In all species studied, afferents from semicircular canals and otolith organs converge on central neurons in the brainstem. However, the spatial and temporal relationships between converging inputs and how these contribute to vestibular behaviors is not well understood. In the current study, we used discrete rotational and translational motion stimuli to characterize canal- and otolith-driven response components of convergent non-eye movement (NEM) neurons in the vestibular nuclear complex of alert pigeons. ⋯ Convergent otolith signals also had similar mean gain and phase values to the afferent population but were spatially well-matched with the corresponding canal signals, cell-by-cell. However, neither response component alone nor a simple linear combination of these components was sufficient to predict actual net responses during combined canal-otolith stimulation. We discuss these findings in the context of previous studies of pigeon vestibular behaviors, and we compare our findings to similar studies in other species.