Neuroscience
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The lateral part of intermediate layer of superior colliculus (SCl) is a critical substrate for successful predation by rats. Hunting-evoked expression of the activity marker Fos is concentrated in SCl while prey capture in rats with NMDA lesions in SCl is impaired. Particularly affected are rapid orienting and stereotyped sequences of actions associated with predation of fast moving prey. ⋯ The predatory behaviour of rats with re-grown whiskers returned to normal. In parallel, Fos expression in SCl induced by predation was significantly reduced in whiskerless animals. We conclude that whiskers contribute to the efficiency of rat prey capture and that the loss of vibrissal input to SCl, as reflected by reduced Fos expression, could play a critical role in predatory deficits of whiskerless rats.
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Memories of learned associations between the rewarding properties of drugs and environmental cues contribute to craving and relapse in humans. The mesocorticolimbic dopamine (DA) system is involved in reward-related learning induced by drugs of abuse. DA D3 receptors are preferentially expressed in mesocorticolimbic DA projection areas. ⋯ In the present study, we show that D3 receptor mutant mice exhibit potentiated acquisition of conditioned place preference (CPP) at low doses of cocaine compared to wild-type mice. Activation of ERK and CaMKIIα, but not the c-Jun N-terminal kinase and p38, in the nucleus accumbens, amygdala and prefrontal cortex is also potentiated in D3 receptor mutant mice compared to that in wild-type mice following CPP expression. These results support a model in which D3 receptors modulate reward-related learning induced by low doses of cocaine by inhibiting activation of ERK and CaMKIIα in reward circuits in the brain.
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During the consolidation of fear memory, it has been shown that GABA(A) receptors (GABA(A)R) are rapidly downregulated in amygdala. This rapid decrease in GABA(A)R functioning may permit transient hyperexcitablity, contributing to cellular mechanisms of memory consolidation. Memory consolidation also requires brain-derived neurotrophic factor (BDNF) activation of tyrosine receptor kinase B (TrkB) receptors in the amygdala and hippocampus. ⋯ By contrast in amygdala cultures, Rp-8-Br-cAMP had no effect. Together, these data suggest that rapid GABA(A)R internalization during memory consolidation is BDNF-TrkB dependent. Further, it appears that hippocampal GABA(A)R internalization is PKA and PKC dependent, while it may be primarily PKC dependent in amygdala, implying differential roles for TrkB-dependent kinase activation in BDNF-dependent memory formation.
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Increasing evidence indicates that both the ATP P2X receptors and adrenergic systems play a very important role in the development of nociception. However, there is little information concerning the interactions between these two systems in the dorsal root ganglia (DRG). In the present study, we examined the effects of noradrenaline (NA) on the P2X3 receptor expression in the DRG of Sprague-Dawley rats. ⋯ In electrophysiological experiments, perfusion of neuronal cultures with the P2X3 agonist (αβ-methylene ATP) increased neuronal firing rate by 139% and 273% in neurons treated with either PBS (control) or NA, respectively, indicating that chronic NA treatment significantly enhanced the neuronal response to P2X3 activation. In behavior studies, combination of NA (2 or 20 nmol) with αβ-methylene ATP (10 nmol) produced a significant and long lasting augmentation of thermal hyperalgesia. These results indicate that NA stimulates P2X3 expression in DRG neurons, and this could contribute to the development of pain sensitization.
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Bone morphogenetic proteins (BMP) are members of the transforming growth factor β (TGF-β) superfamily. BMPs exert its biological functions by interacting with membrane bound receptors belonging to the serine/threonine kinase family including bone morphogenetic protein receptor I (BMPRIA, BMPRIB) and type II (BMPRII). Although BMPR expressions have been well described in the early development of the CNS, little information is available for their expressions in the adult CNS. ⋯ In addition, we found that BAMRIB-IR was preferentially expressed in dendrites of many neurons throughout the CNS, while BMPRIA was mainly expressed in cell bodies, showing that BMPRIA and BMPRIB are differentially targeted in a single neuron. In addition, besides abundant BMPR expressions in neurons, we exhibited BMPR expressions in astrocytes and ependymal cells. These data indicate that BMPRs are more widely expressed throughout the adult CNS than previously reported, and their continued abundant expressions in the adult brain strongly support the idea that BMPRs play pivotal roles also in the adult brain.