Neuroscience
-
Reward-paired optogenetic manipulation of dopamine neurons can increase or decrease behavioral responding to antecedent cues when subjects have the opportunity for new learning, in accordance with a dopamine-mediated error learning signal. Here we examined the impact of reward-paired dopamine neuron inhibition on behavioral responding to reward-predictive cues after subjects had learned. We trained male TH-IRES-Cre mice to lever press for food reward in a progressive ratio procedure, a 2-cue choice procedure, or when continuously reinforced; in all procedures, completion of the response requirement was signaled by an auditory cue presented prior to food delivery. ⋯ Extinction-like behavioral responding was selective for learned associations: it was observed in the 2-cue choice procedure in which each subject was trained on two associations and inhibition was paired with reward for only one of the associations. Thus, inhibition during reward receipt can decrease responding to reward-predictive cues, sharing some features of behavioral extinction. These findings suggest changes in mesolimbic dopaminergic transmission at the time of experienced reward impacts subsequent responding to cues in well-trained subjects as predicted for a learning signal.
-
Neuroglobin (Ngb) is a REST/NRSF-regulated protein, active in reactive oxygen species detoxification and cytochrome c inhibition, which provides a beneficial outcome in pathologies as Alzheimer's disease and strokes. Considering that oxidative stress and cell death are typical hallmarks of amyotrophic lateral sclerosis (ALS), we sought to explore Ngb's involvement along this disease progression. Ngb transcription was detected to be two-fold down-regulated in late-stage SODG93A mice, similarly as previously described for Alzheimer disease. ⋯ To look further into the link between Ngb and ALS, we generated a double mutant Ngb-/-SODG93A mouse model, which shows an earlier onset and severity of hind limb deficits. Mitochondria derived thereof showed an altered mean volume, granularity and Ca2+-induced swelling as compared to NgbWt/WtSODG93A mice. These results indicate Ngb to be involved in and affected by the SOD1G93A pathology, which could in part be attributed to its role in halting destabilizing events of mitochondrial swelling and phenotypes.
-
Hippocampal oscillations, particularly theta (6-12 Hz) and gamma (30-90 Hz) frequency bands, play an important role in several cognitive functions. Theta and gamma oscillations show cross-frequency coupling (CFC), wherein the phase of theta rhythm modulates the amplitude of the gamma oscillation, and this CFC is believed to reflect cell assembly dynamics in cognitive processes. Previous studies have reported that CFC strength correlates with the learning process. ⋯ The enhanced coupling between theta and high-gamma oscillations (60-90 Hz) changed during the late stage of learning. In contrast, the coupling between theta and low-gamma oscillations (30-60 Hz) did not show any changes during learning. These results suggest that the coupling between theta and gamma bands occurs during rule learning and that high- and low-gamma bands play different roles in rule switching.
-
Visual attention enables us to prioritise behaviourally relevant visual information while ignoring distraction. The neural networks supporting attention are modulated by two catecholamines, dopamine and noradrenaline. The current study investigated the effects of single nucleotide polymorphisms in two catecholaminergic genes - COMT (Val158Met) and DBH (444 G/A) - on individual differences in attention functions. ⋯ Furthermore, we demonstrated a significant association between COMT genotype status and effective threshold of visual perception in attentional selection as estimated based on the TVA task performance. No other group differences in attention function were found with respect to the studied genotypes. Overall, our findings provide novel experimental evidence that: (i) dopaminergic and noradrenergic genotypes have dissociable effects on visual attention; (ii) either insufficient or excessive catecholaminergic activity may have equally detrimental effects on sustained attention.
-
The chronic neuropathic pain-associated psychiatric disorders have seriously disturbed the quality of patients' life, such as depression and anxiety. Neuroinflammation in the hippocampus plays an important role in the neuropathic pain-associated depressive and anxiety disorders, but the underlying mechanism has not been thoroughly elucidated to date. The Nod-like receptor protein (NLRP)-1 inflammasome, which controls the production of pro-inflammatory cytokines, was broadly involved in the neuroinflammation-related diseases. ⋯ Functional inhibition of PKR suppressed the NLRP1 inflammasome activation and effectively attenuated the CCI-induced depression-like behaviors. These results indicate that the hippocampal PKR/NLRP1 inflammasome pathway play an important role in the development of the depressive behaviors after chronic neuropathic pain. Thus, interrupting this pathway might provide a novel therapeutic strategy for neuropathic pain-associated depressive disorders.