Current research in neurobiology最新文献

The functional specialization of the ventral stream in Perception and the dorsal stream in Action is the cornerstone of the leading model proposed by Goodale and Milner in 1992. This model is based on neuropsychological evidence and has been a matter of debate for almost three decades, during which the dual-visual stream hypothesis has received much attention, including support and criticism. The advent of functional magnetic resonance imaging (fMRI) has allowed investigating the brain areas involved in Perception and Action, and provided useful data on the functional specialization of the two streams. Research on this topic has been quite prolific, yet no meta-analysis so far has explored the spatial convergence in the involvement of the two streams in Action. The present meta-analysis (N = 53 fMRI and PET studies) was designed to reveal the specific neural activations associated with Action (i.e., grasping and reaching movements), and the extent to which visual information affects the involvement of the two streams during motor control. Our results provide a comprehensive view of the consistent and spatially convergent neural correlates of Action based on neuroimaging studies conducted over the past two decades. In particular, occipital-temporal areas showed higher activation likelihood in the Vision compared to the No vision condition, but no difference between reach and grasp actions. Frontal-parietal areas were consistently involved in both reach and grasp actions regardless of visual availability. We discuss our results in light of the well-established dual-visual stream model and frame these findings in the context of recent discoveries obtained with advanced fMRI methods, such as multivoxel pattern analysis.

Quantifying olfactory impairments can facilitate early detection of Coronavirus disease 2019 (COVID-19). Despite being a debated topic, many reports provide evidence for the neurotropism of SARS-CoV-2. However, a sensitive, specific, and accurate non-invasive method for quantifying persistent neurological impairments is missing to date. To quantify olfactory detectabilities and neurocognitive impairments in symptomatic COVID-19 patients during and post-infection periods, we used a custom-built olfactory-action meter (OAM) providing accurate behavioral readouts. Ten monomolecular odors were used for quantifying olfactory detectabilities and two pairs of odors were employed for olfactory matching tests. We followed cohorts of healthy subjects, symptomatic patients, and recovered subjects for probing olfactory learning deficits, before the Coronavirus Omicron variant was reported in India. Our method identifies severe and persistent olfactory dysfunctions in symptomatic patients during COVID-19 infection. Symptomatic patients and recovered subjects showed significant olfactory learning deficits during and post-infection periods, 4–18 months, in comparison to healthy subjects. On comparing olfactory fitness, we found differential odor detectabilities and olfactory function scores in symptomatic patients and asymptomatic carriers. Our results indicate probable long-term neurocognitive deficits in COVID-19 patients imploring the necessity of long-term tracking during post-infection period. Differential olfactory fitness observed in symptomatic patients and asymptomatic carriers demand probing mechanisms of potentially distinct infection routes.

The network formed by the amygdala (AMG) and the medial Prefrontal Cortex (mPFC), at the interface between our internal and external environment, has been shown to support some important aspects of behavioral adaptation. Whether and how the anatomo-functional organization of this network evolved across primates remains unclear. Here, we compared AMG nuclei morphological characteristics and their functional connectivity with the mPFC in humans and macaques to identify potential homologies and differences between these species. Based on selected studies, we highlight two subsystems within the AMG-mPFC circuits, likely involved in distinct temporal dynamics of integration during behavioral adaptation. We also show that whereas the mPFC displays a large expansion but a preserved intrinsic anatomo-functional organization, the AMG displays a volume reduction and morphological changes related to specific nuclei. We discuss potential commonalities and differences in the dialogue between AMG nuclei and mPFC in humans and macaques based on available data.

The role of thalamocortical circuits in memory has driven a recent burst of scholarship, especially in animal models. Investigating this circuitry in humans is more challenging. And yet, the development of new recording and stimulation technologies deployed for clinical indications has created novel opportunities for data collection to elucidate the cognitive roles of thalamic structures. These technologies include stereoelectroencephalography (SEEG), deep brain stimulation (DBS), and responsive neurostimulation (RNS), all of which have been applied to memory-related thalamic regions, specifically for seizure localization and treatment. This review seeks to summarize the existing applications of neuromodulation of the anterior thalamic nuclei (ANT) and highlight several devices and their capabilities that can allow cognitive researchers to design experiments to assay its functionality. Our goal is to introduce to investigators, who may not be familiar with these clinical devices, the capabilities, and limitations of these tools for understanding the neurophysiology of the ANT as it pertains to memory and other behaviors. We also briefly cover the targeting of other thalamic regions including the centromedian (CM) nucleus, dorsomedial (DM) nucleus, and pulvinar, with associated potential avenues of experimentation.

Future neuroscience and biomedical projects involving non-human primates (NHPs) remain essential in our endeavors to understand the complexities and functioning of the mammalian central nervous system. In so doing, the NHP neuroscience researcher must be allowed to incorporate state-of-the-art technologies, including the use of novel viral vectors, gene therapy and transgenic approaches to answer continuing and emerging research questions that can only be addressed in NHP research models. This perspective piece captures these emerging technologies and some specific research questions they can address. At the same time, we highlight some current caveats to global NHP research and collaborations including the lack of common ethical and regulatory frameworks for NHP research, the limitations involving animal transportation and exports, and the ongoing influence of activist groups opposed to NHP research.

Optogenetics has been a promising and developing technology in systems neuroscience throughout the past decade. It has been difficult though to reliably establish the potential behavioral effects of optogenetic perturbation of the neural activity in nonhuman primates. This poses a challenge on the future of optogenetics in humans as the concepts and technology need to be developed in nonhuman primates first. Here, I briefly summarize the viable approaches taken to improve nonhuman primate behavioral optogenetics, then focus on one approach: improvements in the measurement of behavior. I bring examples from visual behavior and show how the choice of method of measurement might conceal large behavioral effects. I will then discuss the “cortical perturbation detection” task in detail as an example of a sensitive task that can record the behavioral effects of optogenetic cortical stimulation with high fidelity. Finally, encouraged by the rich scientific landscape ahead of behavioral optogenetics, I invite technology developers to improve the chronically implantable devices designed for simultaneous neural recording and optogenetic intervention in nonhuman primates.

Earlier age of cannabis usage poses higher risk of Cannabis Use Disorder and adverse consequences, such as addiction, anxiety, dysphoria, psychosis, largely attributed to its principal psychoactive component, Δ9-tetrahydrocannabinol (THC) and altered dopaminergic function. As dopamine D1-D2 receptor heteromer activation causes anxiety and anhedonia, this signaling complex was postulated to contribute to THC-induced affective symptoms. To investigate this, we administered THC repeatedly to adolescent monkeys and adolescent or adult rats. Drug-naïve adolescent rat had lower striatal densities of D1-D2 heteromer compared to adult rat. Repeated administration of THC to adolescent rat or adolescent monkey did not alter D1-D2 heteromer expression in nucleus accumbens or dorsal striatum but upregulated it in adult rat. Behaviourally, THC-treated adult, but not adolescent rat manifested anxiety and anhedonia-like behaviour, with elevated composite negative emotionality scores that correlated with striatal D1-D2 density. THC modified downstream markers of D1-D2 activation in adult, but not adolescent striatum. THC administered with cannabidiol did not alter D1-D2 expression. In adult rat, co-administration of CB1 receptor (CB1R) inverse agonist with THC attenuated D1-D2 upregulation, implicating cannabinoids in the regulation of striatal D1-D2 heteromer expression. THC exposure revealed an adaptable age-specific, anxiogenic, anti-reward mechanism operant in adult striatum but deficient in adolescent rat and monkey striatum that may confer increased sensitivity to THC reward in adolescence while limiting its negative effects, thus promoting continued use and increasing vulnerability to long-term adverse cannabis effects.

The chromodomain helicase DNA-binding protein 8 (CHD8) is a chromatin remodeler whose mutation is associated, with high penetrance, with autism. Individuals with CHD8 mutations share common symptoms such as autistic behaviour, cognitive impairment, schizophrenia comorbidity, and phenotypic features such as macrocephaly and facial defects. Chd8-deficient mouse models recapitulate most of the phenotypes seen in the brain and other organs of humans. It is known that CHD8 regulates - directly and indirectly - neuronal, autism spectrum disorder (ASDs)-associated genes and long non-coding RNAs (lncRNAs) genes, which, in turn, regulate fundamental aspects of neuronal differentiation and brain development and function. A major characteristic of CHD8 regulation of gene expression is its non-linear and dosage-sensitive nature. CHD8 mutations appear to affect males predominantly, although the reasons for this observed sex bias remain- unknown. We have recently reported that CHD8 directly regulates X chromosome inactivation (XCI) through the transcriptional control of the Xist long non-coding RNA (lncRNA), the master regulator of mammalian XCI. We identified a role for CHD8 in regulating accessibility at the Xist promoter through competitive binding with transcription factors (TFs) at Xist regulatory regions. We speculate here that CHD8 might also regulate accessibility at neuronal/ASD targets through a similar competitive binding mechanism during neurogenesis and brain development. However, whilst such a model can reconcile the phenotypic differences observed in Chd8 knock-down (KD) vs knock-out (KO) mouse models, explaining the observed CHD8 non-linear dosage-dependent activity, it cannot on its own explain the observed disease sex bias.

Type 2 diabetes mellitus has steadily increased in prevalence over the past five decades. Among the health risks associated with this disorder are cognitive decline and are increased risk of developing dementia. To further investigate the link between diabetes and cognition, here we test memory performance and hippocampal function in the Goto-Kakizaki (GK) rat, a robust model of diabetes. Relative to age-matched Wistar rats, GK rats show impairments in a conjunctive memory task that requires discriminating objects not only on the basis of their physical characteristics, but also on the basis of where and when they were last seen. Concomitant to these deficits are changes in the pattern of expression of Egr1 (an immediate-early gene critical for memory) in dentate gyrus granule cells, consistent with dentate hypoactivity leading to unstable hippocampal representations. These data support the hypothesis that diabetes confers a phenotype of accelerated senescence on the hippocampus, and help to link this disorder with changes in hippocampal circuits.