Neuroscience
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During development, Purkinje axons elongate along precise trajectories and acquire stereotypic branching patterns to innervate targets in the deep nuclei and cerebellar cortex. These processes are accomplished through cell-intrinsic mechanisms, whose operation is regulated by environmental signaling cues. Here, we show that Anosmin-1, the protein defective in the X-linked form of Kallmann syndrome, is one among such cues. ⋯ Comparable results are obtained by administering the protein or the blocking antibodies to organotypic cultures of postnatal (P0) rat cerebellum. In P10 cerebellar slices, Anosmin-1 does not enhance the spontaneous regenerative capabilities of severed Purkinje axons, but promotes the terminal outgrowth of injured neurites into embryonic neocortical explants apposed to the axotomy site. Although Anosmin-1 is unable to change the overall intrinsic growth competence of Purkinje cells, it exerts a powerful stimulatory action on the budding and extension of collateral branches and terminal plexus, contributing to the patterning of Purkinje axons.
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Chronic neuropathic pain remains an unmet clinical problem because it is often resistant to conventional analgesics. Metabotropic glutamate receptors (mGluRs) are involved in nociceptive processing at the spinal level, but their functions in neuropathic pain are not fully known. In this study, we investigated the role of group III mGluRs in the control of spinal excitatory and inhibitory synaptic transmission in a rat model of neuropathic pain induced by L5/L6 spinal nerve ligation. ⋯ Furthermore, l-AP4 similarly inhibited the frequency of GABAergic and glycinergic IPSCs in control and nerve-injured rats. Our study suggests that spinal nerve injury augments glutamatergic input from primary afferents but decreases GABAergic and glycinergic input to spinal dorsal horn neurons. Activation of group III mGluRs attenuates glutamatergic input from primary afferents in nerve-injured rats, which could explain the antinociceptive effect of group III mGluR agonists on neuropathic pain.
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The endocannabinoid system is a neuromodulatory system which controls the release of multiple neurotransmitters, including glutamate and both, the endocannabinoid and glutamatergic systems, have been implicated in alcohol relapse. Cannabinoid agonists induce an increase in relapse-like drinking whereas glutamate receptor antagonists could prevent it. Here we hypothesize that cannabinoid-induced increases in relapse-like alcohol drinking could be mediated by glutamatergic N-methyl-d-aspartate (NMDA) receptors. ⋯ Interestingly, such changes were blocked after L-701 treatment. Finally, WIN treatment also caused a reduction in NR1 mRNA levels in the amygdala. In conclusion, pharmacological inactivation of the glycine-binding site of NMDA receptors may control cannabinoid-induced relapse-like drinking, which is associated with altered expression of CNR1 and NR1 gene expression as observed after WIN treatment.
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Lack of sexual interest is the most common sexual complaint among women. However, factors affecting sexual desire in women have rarely been studied. While the role of the brain in integrating the sensory, attentional, motivational, and motor aspects of sexual response is commonly acknowledged as important, little is known about specific patterns of brain activation and sexual interest or response, particularly among women. ⋯ Findings were consistent across the three experimental sessions. The results suggest differences between women with NHSD and HSDD in encoding arousing stimuli, retrieval of past erotic experiences, or both. The findings of greater activation in BA 10 and BA 47 among women with HSDD suggest that this group allocated significantly more attention to monitoring and/or evaluating their responses than NHSD participants, which may interfere with normal sexual response.
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One way of investigating affective learning is the use of aversive pictures as unconditioned stimuli (UCS) in conditioning paradigms. In the last decades, there has been a heated debate on the influence of contingency awareness on conditioned responses (CRs). Only a few studies found CRs in contingency unaware subjects whereas other studies only reported conditioned reactions in contingency aware participants. ⋯ Investigation of SCRs and valence ratings revealed that only aware participants showed conditioned reactions. Our results point toward dissociations between response levels (e.g. brain activity) not affected by contingency awareness and more cognitive response levels (e.g. subjective ratings and SCRs) which are affected by contingency awareness. As a unique finding in human aversive conditioning, we discuss the role of the nucleus accumbens as well as practical implications for affective learning models.