Neuroscience
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In hippocampus, two guanylyl cyclases (NO-GC1 and NO-GC2) are involved in the transduction of the effects of nitric oxide (NO) on synaptic transmission. However, the respective roles of the NO-GC isoforms on synaptic transmission are less clear in other regions of the brain. In the present study, we used knock-out mice deficient for the NO-GC1 isoform (NO-GC1 KO) to analyze its role in the glutamatergic and GABAergic neurotransmission at pyramidal neurons in layers II/III of somatosensory cortex. ⋯ By blocking postsynaptic NMDA receptors, the NMDA receptor-dependent NO signal was shown to be linked to the effect of NO-GC1 on presynaptic GABA release. Of note, the balance between glutamatergic and GABAergic inputs at individual synapses remained unaltered in the NO-GC1 KO mice. In sum, our results indicate a role for cGMP generated by presynaptic localized NO-GC1 to adjust inhibitory and excitatory inputs at individual synapses in the somatosensory cortex.
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Adolescence is accompanied by the maturation of several stress-responsive areas of the brain including the amygdala, a key region for the acquisition and expression of conditioned fear. These changes may contribute to the development of stress-related disorders in adolescence, such as anxiety and depression, and increase the susceptibility to these psychopathologies later in life. Here, we assessed the effects of acute restraint stress on fear learning and amygdala activation in pre-adolescent and adult male rats. ⋯ At the cellular level, the combination of stress and fear conditioning resulted in a greater number of FOS-positive cells in the basolateral nucleus of the amygdala (BLA) than fear conditioning alone, and this increase was greater in pre-adolescents than in adults. Despite age-dependent differences, we found no changes in glucocorticoid receptor (GR) levels in the amygdala of either pre-adolescent or adult males. Overall, our data indicate that stress prior to fear conditioning leads to extinction-resistant fear responses in pre-adolescent animals, and that the BLA may be one neural locus mediating these age-dependent effects of stress on fear learning.
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The mode of action of L-DOPA on excitatory synaptic transmission in second-order neurons of the nucleus tractus solitarius (NTS) was studied using the rat brainstem slices. Superfusion of L-DOPA (10μM) reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) without any effect on the amplitude. A low concentration (1μM) was ineffective on the mEPSCs, and the highest concentration (100μM) exerted a stronger inhibitory effect. ⋯ The effects of L-DOPA were blocked by a competitive antagonist, L-DOPA methyl ester (100μM) and also by a D2 receptor antagonist, sulpiride (10μM), while those of dopamine were blocked by the latter but not by the former. In reserpine (5mg/kg, s.c.)-treated rats, the effects of L-DOPA on both mEPSCs and eEPSCs were completely abolished, but those of dopamine remained unchanged. The present results suggest a possibility that L-DOPA may induce the release of dopamine from the axon terminals in the NTS and the released dopamine suppresses the glutamatergic transmission through activation of the presynaptic D2 receptors.
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Prostaglandin E2 (PGE2) promotes gonadotropin secretion by regulating the activity of neurons that release gonadotropin-releasing hormone (GnRH) in the hypothalamus. However, the mechanisms of action of PGE2 at these neurons have yet to be fully explored. We examined the effects of PGE2 on the generation of miniature excitatory postsynaptic currents (mEPSCs) at GnRH neurons as measured by whole-cell, patch-clamp recordings. ⋯ Subsequent experiments to identify candidate receptors for PG2E's action revealed that exposure to a PGE2 receptor 4 (EP4) agonist, but not EP1 or EP2 agonists, mimicked the effects achieved by PGE2 exposure. These effects of mEPSCs could be reversed using an EP4 antagonist, illustrating the specificity of the effect. Collectively, these data demonstrate that PGE2 can alter excitatory synaptic neurotransmission at GnRH neurons via EP4 signaling at presynaptic site(s) in an estrogen-dependent fashion during proestrus.
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The tyrosine kinases of the Syk family are essential components of the well-characterized immunoreceptor ITAM-based signaling pathway. However, ITAM-based signaling typically does not function in isolation. Instead, it is enmeshed in the molecular network controlling cellular adhesion and chemotaxis. ⋯ Syk phosphorylation was induced by EphB2 engagement and locally turned down by a not yet identified factor that could in part explain the restricted pattern of Syk phosphorylation observed along GC migratory route. Whereas Syk kinase activity appeared not essential for ephrin/Eph-mediated axon extension, it might provide polarization signals required for proper nucleus translocation during GC migration. In conclusion, Syk kinase acts downstream of receptors controlling GC tangential migration.