Human brains interpret external stimuli based on internal representations. One untested hypothesis is that the default-mode network (DMN), widely considered responsible for internally oriented cognition, can decode external information. Here, we posit that the unique structural and functional fingerprint of the precuneus (PCu) supports a prominent role for the posterior part of the DMN in this process. By analyzing the imaging data of 100 participants performing two attention-demanding tasks, we found that the PCu is functionally divided into dorsal and ventral subdivisions. We then conducted a comprehensive examination of their connectivity profiles and found that at rest, both the ventral PCu (vPCu) and dorsal PCu (dPCu; d/vPCu) are mainly connected with the DMN but also are differentially connected with internally oriented network (IoN) and externally oriented network (EoN). During tasks, the double associations between the d/vPCu and the IoN/EoN are correlated with task performance and can switch depen...

Nescient helix-loop-helix 2 (NHLH2) is a hypothalamic transcription factor that controls the expression of prohormone convertase 1/3, therefore having an impact on the processing of proopiomelanocortin and thus on energy homeostasis. Studies have shown that knockout of Nhlh2 results in increased body mass, reduced physical activity and hypogonadism. In humans, a polymorphism of the NHLH2 gene is associated with obesity, and in Prader-Willi syndrome, a condition characterized by obesity, hypogonadism and behavioral abnormalities, the expression of NHLH2 is reduced. Despite clinical and experimental evidence suggesting that NHLH2 could be a good target for the treatment of obesity, no previous study has evaluated the impact of NHLH2 overexpression in obesity. Here, in mice fed a high-fat diet introduced right after the arcuate nucleus intracerebroventricular injection of a lentivirus that promoted 40% increase in NHLH2, there was prevention of the development of obesity by a mechanism dependent on the reduct...

The hippocampal region has long been considered critical for memory of time, and recent evidence shows that network operations and single unit activity in the hippocampus (HIPP) and medial entorhinal cortex (MEC) correlate with elapsed time. However, whether the MEC activity is necessary for timing remains largely unknown. Here we expressed DREADDs under the CAMKIIa promoter to preferentially target MEC excitatory neurons for chemogenetic silencing, while freely moving male rats reproduced a memorized time interval by waiting inside a ROI (region of interest). We found that such silencing impaired the reproduction of the memorized interval and led to an overestimation of elapsed time. Trial history analyses under this condition revealed a reduced influence of previous trials on current waiting times, suggesting an impairment in maintaining temporal memories across trials. Moreover, using GLM (logistic regression) we show that decoding behavioral performance from preceding waiting times was significantly co...

The auditory cortex (AC) sends long-range projections to virtually all subcortical auditory structures. One of the largest and most complex of these - the projection between AC and inferior colliculus (IC, the corticocollicular pathway) - originates from layer 5 and deep layer 6. Though previous work has shown that these two corticocollicular projection systems have different physiological properties and network connectivities, their functional organization is poorly understood. Here, using a combination of traditional and viral tracers combined with in vivo imaging in both sexes of the mouse, we observed that layer 5 and layer 6 corticocollicular neurons differ in their areas of origin and termination patterns. Layer 5 corticocollicular neurons are concentrated in primary AC while layer 6 corticocollicular neurons emanate from broad auditory and limbic areas in the temporal cortex. In addition, layer 5 sends dense projections of both small and large (> 1 µm2 area) terminals to all regions of non-lemniscal...

Entorhinal cortical projections show segregation along the transverse axis of CA1, with the medial entorhinal cortex (MEC) sending denser projections to proximal CA1 (pCA1) and the lateral entorhinal cortex (LEC) sending denser projections to distal CA1 (dCA1). Previous studies have reported functional segregation along the transverse axis of CA1 correlated with the functional differences in MEC and LEC. pCA1 shows higher spatial selectivity than dCA1 in these studies. We employ a double rotation protocol, which creates an explicit conflict between the local and the global cues, to understand the differential contributions of these reference frames to the spatial code in pCA1 and dCA1 in male Long Evans rats. We show that pCA1 and dCA1 respond differently to this local-global cue conflict. pCA1 representation splits as predicted from the strong conflicting inputs it receives from MEC and distal CA3 (dCA3). In contrast, dCA1 rotates more in concert with the global cues. In addition, pCA1 and dCA1 display co...

Cognitive control is crucially involved in making (dis)honest decisions. However, the precise nature of this role has been hotly debated. Is honesty an intuitive response, or is will power needed to override an intuitive inclination to cheat? A reconciliation of these conflicting views proposes that cognitive control enables dishonest participants to be honest, whereas it allows those who are generally honest to cheat. Thus, cognitive control does not promote (dis)honesty per se; it depends on one's moral default. In the present study, we tested this proposal using electroencephalograms in humans (males and females) in combination with an independent localizer (Stroop task) to mitigate the problem of reverse inference. Our analysis revealed that the neural signature evoked by cognitive control demands in the Stroop task can be used to estimate (dis)honest choices in an independent cheating task, providing converging evidence that cognitive control can indeed help honest participants to cheat, whereas it fa...

Ana Rita Nunes, Michael Gliksberg, Susana A. M. Varela, Magda Teles, Einav Wircer, et al. (see pages [8742–8760][1]) Oxytocin has important roles in social behaviors, such as pair-bonding, parenting, social affiliation, and aggression, in birds and mammals. It also regulates stress responses,

The ability to stop an already initiated action is paramount to adaptive behavior. Much scientific debate in the field of human action-stopping currently focuses on two interrelated questions. (1) Which cognitive and neural processes uniquely underpin the implementation of inhibitory control when actions are stopped after explicit stop signals, and which processes are instead commonly evoked by all salient signals, even those that do not require stopping? (2) Why do purported (neuro)physiological signatures of inhibition occur at two different latencies after stop signals? Here, we address both questions via two preregistered experiments that combined measurements of corticospinal excitability, EMG, and whole-scalp EEG. Adult human subjects performed a stop signal task that also contained “ignore” signals: equally salient signals that did not require stopping but rather completion of the Go response. We found that both stop- and ignore signals produced equal amounts of early-latency inhibition of corticosp...

Apolipoprotein E (APOE), one of the primary lipoproteins in the brain has three isoforms in humans, APOE2, APOE3, and APOE4. APOE4 is the most well-established risk factor increasing the predisposition for Alzheimer's disease (AD). The presence of the APOE4 allele alone is shown to cause synaptic defects in neurons and recent studies have identified multiple pathways directly influenced by APOE4. However, the mechanisms underlying APOE4-induced synaptic dysfunction remain elusive. Here, we report that the acute exposure of primary cortical neurons or synaptoneurosomes to APOE4 leads to a significant decrease in global protein synthesis. Primary cortical neurons were derived from male and female embryos of Sprague Dawley (SD) rats or C57BL/6J mice. Synaptoneurosomes were prepared from P30 male SD rats. APOE4 treatment also abrogates the NMDA-mediated translation response indicating an alteration of synaptic signaling. Importantly, we demonstrate that both APOE3 and APOE4 generate a distinct translation resp...