Neuroscience
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Studies on classification learning suggested that altered dopamine function in Parkinson's Disease (PD) specifically affects learning from feedback. In patients OFF medication, enhanced learning from negative feedback has been described. This learning bias was not seen in observational learning from feedback, indicating different neural mechanisms for this type of learning. ⋯ Also, patients and controls showed comparable evidence of feedback processing in observational learning. In active feedback learning, PD patients use alternative learning strategies than healthy controls. Analyses on observational learning did not yield differences between patients and controls, adding to recent evidence of a differential role of the human striatum in active and observational learning from feedback.
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Neurons containing the neuronal nitric oxide synthase (nNOS) enzyme are located in brain areas related to defensive behavior, such as the ventromedial prefrontal cortex (vMPFC). Rats exposed to a live predator (a cat) present anxiety-like behavior and an increased number of nNOS-positive neurons in this brain area one-week later. Moreover, stress-related behavioral changes in rodents can be prevented by systemic or local vMPFC nNOS inhibition. ⋯ Moreover, open-arm exploration of the EPM was negatively correlated with nNOS expression (p<0.05) and NOx levels (p<0.05) in the PL. The anxiogenic-like effect observed 24h after RS was prevented by NPLA (p<0.05). Our results suggest that RS-induced anxiogenic-like effect might depend on increased nNOS-mediated signaling in the PL MPFC.
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Women of child-bearing age are the population group at highest risk for depression. In pregnant women, fluoxetine (Flx) is the most widely prescribed selective serotonin reuptake inhibitor (SSRI) used for the treatment of depression. While maternal stress, depression, and Flx exposure have been shown to effect neurodevelopment of the offspring, separately, combined effects of maternal stress and Flx exposure have not been extensively examined. The present study investigated the effects of prenatal maternal stress and perinatal exposure to the SSRI Flx on the behavior of male mice as adults. ⋯ Maternal behavior was not altered by either stress or Flx treatment. Treatment of the mother with Flx led to detectible Flx and NorFlx levels and lead to a decrease in serotonin levels in pup brains. In the adult male offspring, while perinatal exposure to Flx increased aggressive behavior, prenatal maternal stress decreased aggressive behavior. Interestingly, the combined effects of stress and Flx normalized aggressive behavior. Furthermore, perinatal Flx treatment led to a decrease in anxiety-like behavior in male offspring. PS led to hyperactivity and a decrease in BDNF levels in the frontal cortex regardless of Flx exposure. Neither maternal stress or Flx altered offspring performance in tests of cognitive abilities, memory, sensorimotor information processing, or risk assessment behaviors. These results demonstrate that maternal exposure to stress and Flx have a number of sustained effects on the male offspring.
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Prostaglandin-E2 (PGE2) is a very important inflammatory mediator and PGE2-mediated neuroexcitation in sex-specific distribution of Ah-type trigeminal ganglion neurons (TGNs) isolated from adult female rats is not fully addressed. The whole-cell patch-clamp experiment was performed to verify the effects of PGE2, forskolin, and GPR30-selective agonist (G-1) on action potential (AP) and tetrodotoxin-resistant (TTX-R) Na(+) currents in identified Ah-type TGNs. The results showed that the firing frequency was increased in Ah- and C-types by PGE2, which was simulated by forskolin and inhibited by Rp-cyclic adenosine monophosphate (cAMP), while G-1 mimicked this effect only in Ah-types, which was abolished by GPR30-selective antagonist (G-15). ⋯ Intriguingly, the low-threshold persistent TTX-R component was activated from -60 mV and increased almost double at -30 mV compared with ∼30-40% increment of TTX-R component being activated at ∼-10 mV. Additionally, the change in TTX-R component of Ah-types was equivalent well with that in C-type TGNs. Taken these data together, we conclude that PGE2 modulates the neuroexcitation via cAMP-mediated upregulation of TTX-R Na(+) currents in both cell-types with hormone-dependent feature, especially persistent TTX-R Na(+) currents in sex-specific distribution of myelinated Ah-type TGNs.
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cAMP response-element binding protein (CREB)-dependent genes are differentially expressed in brains of temporal lobe epilepsy (TLE) patients and also in animal models of TLE. Previous studies have demonstrated the importance of CREB regulated transcription in TLE. However, the role of the key regulator of CREB activity, CREB-regulated transcription coactivator 1 (CRTC1), has not been explored in epilepsy. ⋯ At 48 h after SE, FK506 treatment blocked CRTC1 nuclear localization and dephosphorylation of Ser151. Our results provide evidence that CREB cofactor CRTC1 translocates into the nucleus of a distinct subset of hippocampal neurons during and following SE and this translocalization is regulated by calcineurin at a later time point following SE. Nuclear CRTC1 can bind to CREB possibly altering transcription during epileptogenesis.