Neuroscience
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Spinal cord stimulation (SCS) is used clinically to treat neuropathic pain states, but the precise mechanism by which it attenuates neuropathic pain remains to be established. The profile of afferent fiber activation during SCS and how it may correlate with the efficacy of SCS-induced analgesia are unclear. After subjecting rats to an L5 spinal nerve ligation (SNL), we implanted a miniature quadripolar electrode similar to that used clinically. ⋯ Results showed that three consecutive days of SCS treatment (50 Hz, 0.2 ms, 30 min, 80-90% of MoT), but not sham stimulation, gradually alleviated mechanical hypersensitivity in SNL rats. The MoT obtained in the animal behavioral study was significantly less than the Aα/β-threshold of the compound AP determined during electrophysiological recording, suggesting that SCS could attenuate mechanical hypersensitivity with a stimulus intensity that recruits only a small fraction of the A-fiber population in SNL rats. Although both the MoT and compound AP threshold were similar between responders and nonresponders, the size of the compound AP waveform at higher stimulation intensities was larger in the responders, indicating a more efficient activation of the dorsal column structure in responders.
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Pregnant rats were treated daily with 1 g/L of L-glutamate in their drinking water during pregnancy and/or lactation. The effect on adenosine A₁ receptor (A₁R) and A(2A) receptor (A(2A)R) in brains from both mothers and 15-day-old neonates was assayed using radioligand binding and real time PCR assays. Mothers receiving L-glutamate during gestation, lactation, and throughout gestation and lactation showed a significant decrease in total A₁R number (water+water, 302±49 fmol/mg; L-glutamate+water, 109±11 fmol/mg, P<0.01; water+L-glutamate, 52±13 fmol/mg, P<0.01; L-glutamate+L-glutamate, 128±33 fmol/mg, P<0.05). ⋯ Concerning adenosine A(2A)R, radioligand binding assays revealed that Bmax parameter was significantly increased in male and female neonates exposed to L-glutamate during lactation (male neonates: water+water, 214±23 fmol/mg; water+L-glutamate, 581±49 fmol/mg; P<0.01; female neonates: water+water, 51±10 fmol/mg; water+L-glutamate, 282±52 fmol/mg; P<0.05). No variations were found in mRNA level coding adenosine A(2A)R in maternal or neonatal brain. In summary, long-term L-glutamate treatment during gestation and lactation promotes a significant down-regulation of A₁R in whole brain from both mother and neonates and a significant up-regulation of A(2A)R in neonates exposed to L-glutamate during lactation.
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This study examined whether individual differences in aerobic fitness are associated with differences in activation of cognitive control brain networks in preadolescent children. As expected, children performed worse on a measure of cognitive control compared with a group of young adults. However, individual differences in aerobic fitness were associated with cognitive control performance among children. ⋯ Brain activation was compared between performance-matched groups of lower- and higher-fit children. Fitness groups differed in brain activity for regions associated with response execution and inhibition, task set maintenance, and top-down regulation. Overall, differing activation patterns coupled with different patterns of brain-behavior correlations suggest an important role of aerobic fitness in modulating task strategy and the efficiency of neural networks that implement cognitive control in preadolescent children.
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Central chemoreflex stimulation produces an increase in phrenic nerve activity (PNA) and sympathetic nerve activity (SNA). The A5 noradrenergic region projects to several brainstem areas involved in autonomic regulation and contributes to the increase in SNA elicited by peripheral chemoreflex activation. The aim of the present study was to further test the hypothesis that the A5 noradrenergic region could contribute to central chemoreflex activation. ⋯ Injections of the immunotoxin anti-dopamine β-hydroxylase-saporin (anti-DβH-SAP) into the A5 region destroyed TH⁺ neurons but spared facial motoneurons and the chemosensitive neurons in the retrotrapezoid nucleus that express the transcription factor Phox2b and that are non-catecholaminergic (TH⁻Phox2b⁺). Two weeks after selective destruction of the A5 region with the anti-DβH-SAP toxin, the increase in MAP (Δ=+22±5 mmHg, P<0.05), sSNA (Δ=+68±9%, P<0.05), and PNA amplitude was reduced after central chemoreflex activation. These results suggest that A5 noradrenergic neurons contribute to the increase in MAP, sSNA, and PNA activation during central chemoreflex stimulation.
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Previous research suggests the infralimbic cortex is important in situations when there is competition between goal-directed and habitual responding. Here we used a response conflict procedure to further explore the involvement of the infralimbic cortex in this relationship. Rats received training on two instrumental biconditional discriminations, one auditory and one visual, in two distinct contexts. ⋯ Rats receiving control infusions into the infralimbic cortex showed a significant interference effect, producing more responses to the over-trained (habitual), but context-inappropriate, stimulus element of the incongruent compound. This interference effect was abolished by inactivation of the infralimbic cortex; animals showed a reduced tendency to produce the habitual but inappropriate response compared with animals receiving control infusions. This finding provides evidence that the infralimbic cortex is involved in attenuating the influence of goal-directed behavior, for example context-appropriate responding.