Neuroscience
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Mesolimbic dopamine has been implicated in reward learning. Fischbach-Weiss and Janak (this issue) use optogenetics to attenuate dopamine signaling and study its role in cue-driven motivated behavior.
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Serotonin is a neurotransmitter that plays a role in regulating activities such as sleep, appetite, mood and substance abuse disorders; serotonin receptors 5-HT2AR and 5-HT2CR are active within pathways associated with substance abuse. It has been suggested that 5-HT2AR and 5-HT2CR may form a dimer that affects behavioral processes. Here we study the coevolution of residues in 5-HT2AR and 5-HT2CR to identify potential interactions between residues in both proteins. ⋯ We also discuss how co-expression of the receptors suggests the predicted interaction is functional. Finally, we analyze how several single nucleotide polymorphisms for the 5-HT2AR and 5-HT2CR genes affect their interaction. Our findings are the first to characterize the binding interface of 5-HT2AR/5-HT2CR and indicate a correlation between this interface and location of SNPs in both proteins.
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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.
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Explanations of memory-guided navigation in rodents typically suggest that cue- and place-based navigations are independent aspects of behavior and neurobiology. The results of many experiments show that hippocampal damage causes both anterograde and retrograde amnesia (AA; RA) for place memory, but only RA for cue memory. In the present experiments, we used a concurrent cue-place water task (CWT) to study the effects of hippocampal damage before or after training on cue- and place-guided navigation, and how cue and place memory interact in damaged and control rats. ⋯ By contrast to these anterograde effects, damage made after training causes RA for cue choice accuracy and latency to navigate to the correct cue. In addition, the extent of hippocampal damage predicted impairments in choice accuracy when lesions were made after training. These data extend previous work on the role of the hippocampus in cue and place memory-guided navigation, and show that the hippocampus plays an important role in both aspects of memory and navigation when present during the learning experience.
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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.