Disparate processing of numerosity and associated continuous magnitudes in rats.

The studies of number sense in different species are severely hampered by the inevitable entanglement of non-numerical attributes inherent in nonsymbolic stimuli representing numerosity, resulting in contrasting theories of numerosity processing. Here, we developed an algorithm and associated analytical methods to generate stimuli that not only minimized the impact of non-numerical magnitudes in numerosity perception but also allowed their quantification. We trained number-naïve rats with these stimuli as sound pulses representing two or three numbers and demonstrated that their numerical discrimination ability mainly relied on numerosity. Also, studying the learning process revealed that rats used numerosity before using magnitudes for choices. This numerical processing could be impaired specifically by silencing the posterior parietal cortex. Furthermore, modeling this capacity by neural networks shed light on the separation of numerosity and magnitudes extraction. Our study helps dissect the relationship between magnitude and numerosity processing, and the above different findings together affirm the independent existence of innate number and magnitudes sense in rats.

Therapeutic effect of a histone demethylase inhibitor in Parkinson's disease.

Iron accumulation in the substantia nigra is recognized as a hallmark of Parkinson's disease (PD). Therefore, reducing accumulated iron and associated oxidative stress is considered a promising therapeutic strategy for PD. However, current iron chelators have poor membrane permeability and lack cell-type specificity. Here we identified GSK-J4, a histone demethylase inhibitor with the ability to cross blood brain barrier, as a potent iron suppressor. Only a trace amount of GSK-J4 significantly and selectively reduced intracellular labile iron in dopaminergic neurons, and suppressed H2O2 and 6-OHDA-induced cell death in vitro. The iron-suppressive effect was mainly mediated by inducing an increase in the expression of the iron exporter ferroportin-1. In parallel, GSK-J4 rescued dopaminergic neuron loss and motor defects in 6-OHDA-induced PD rats, which was accompanied by reduction of oxidative stress. Importantly, GSK-J4 rescued the abnormal changes of histone methylation, H3K4me3 and H3K27me3 during 6-OHDA treatment although the iron-suppressive and neuroprotective effects were sensitive to H3K4me3 inhibition only. Also, upregulating H3K4me3 increased ferroportin-1 expression and neuroprotection. Taken together, we demonstrate a previously unappreciated action of GSK-J4 on cell-specific iron suppression and neuroprotection via epigenetic mechanism. Compared with conventional iron chelators, this compound has a stronger therapeutic potential for PD.

A limbic circuitry involved in emotional stress-induced grooming.

Prolonged exposure to negative stressors could be harmful if a subject cannot respond appropriately. Strategies evolved to respond to stress, including repetitive displacement behaviours, are important in maintaining behavioural homoeostasis. In rodents, self-grooming is a frequently observed repetitive behaviour believed to contribute to post-stress de-arousal with adaptive value. Here we identified a rat limbic di-synaptic circuit that regulates stress-induced self-grooming with positive affective valence. This circuit links hippocampal ventral subiculum to ventral lateral septum (LSv) and then lateral hypothalamus tuberal nucleus. Optogenetic activation of this circuit triggers delayed but robust excessive grooming with patterns closely resembling those evoked by emotional stress. Consistently, the neural activity of LSv reaches a peak before emotional stress-induced grooming while inhibition of this circuit significantly suppresses grooming triggered by emotional stress. Our results uncover a previously unknown limbic circuitry involved in regulating stress-induced self-grooming and pinpoint a critical role of LSv in this ethologically important behaviour.