Racism is a threat to public health. Race is a sociopolitical construct that has been used for generations to create disparities in educational access, housing conditions, exposure to environmental contaminants, and access to health care. Collectively, these disparities have a negative impact on the health of non-white Americans. The National Institutes of Health (NIH) funds biomedical research, including basic neuroscience research, aimed at understanding the mechanisms and consequences of health and disease in Americans. NIH has recently acknowledged its own structural racism, the disadvantage this perpetuates in the biomedical research enterprise, and has announced its commitment to eliminating these disparities. Here, we discuss different rates of disease in U.S. citizens from different racial backgrounds. We next describe ways in which the biomedical research enterprise (1) has contributed to health disparities and (2) can contribute to the solving this problem. Based on our own scientific expertise, ...

We report that the neurotrophin receptor p75 contributes to sensory neuron survival through the regulation of cholesterol metabolism in Schwann cells. Selective deletion of p75 in mouse Schwann cells of either sex resulted in a 30% loss of dorsal root ganglia (DRG) neurons and diminished thermal sensitivity. P75 regulates Schwann cell cholesterol biosynthesis in response to BDNF, forming a co-receptor complex with ErbB2 and activating ErbB2-mediated stimulation of sterol regulatory element binding protein 2 (SREBP2), a master regulator of cholesterol synthesis. Schwann cells lacking p75 exhibited decreased activation of SREBP2 and a reduction in 7-dehydrocholesterol (7-DHC) reductase (DHCR7) expression, resulting in accumulation of the neurotoxic intermediate, 7-dehyrocholesterol in the sciatic nerve. Restoration of DHCR7 in p75 null Schwann cells in mice significantly attenuated DRG neuron loss. Together, these results reveal a mechanism by which the disruption of lipid metabolism in glial cells negativel...

Galanin, one of the most inducible neuropeptides, is widely present in developing brains, and its expression is altered by pathologic events (e.g., epilepsy, ischemia, and axotomy). The roles of galanin in brain development under both normal and pathologic conditions have been hypothesized, but the question of how galanin is involved in fetal and early postnatal brain development remains largely unanswered. In this study, using granule cell migration in the cerebellum of early postnatal mice (both sexes) as a model system, we examined the role of galanin in neuronal cell migration during normal development and after brain injury. Here we show that, during normal development, endogenous galanin participates in accelerating granule cell migration via altering the Ca2+ and cAMP signaling pathways. Upon brain injury induced by the application of cold insults, galanin levels decrease at the lesion sites, but increase in the surroundings of lesion sites. Granule cells exhibit the following corresponding changes ...

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...

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...

Errors that result from a mismatch between predicted movement outcomes and sensory afference are used to correct ongoing movements through feedback control and to adapt feedforward control of future movements. The cerebellum has been identified as a critical part of the neural circuit underlying implicit adaptation across a wide variety of movements (reaching, gait, eye movements, and speech). The contribution of this structure to feedback control is less well understood. Although it has recently been shown in the speech domain that individuals with cerebellar degeneration produce larger online corrections for sensory perturbations than control participants, similar behavior has not been observed in other motor domains. Currently, comparisons across domains are limited by different population samples and potential ceiling effects in existing tasks. To assess the relationship between changes in feedforward and feedback control associated with cerebellar degeneration across motor domains, we evaluated adapti...

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...