Neuroinflammation has been widely recognized as the primary pathophysiological mechanism underlying ischemic white matter lesions (IWML) in chronic cerebral hypoperfusion (CCH). Adenosine A2A receptor (A2aR), an important adenosine receptor, exhibits a dual role in neuroinflammation by modulating both proinflammatory and anti-inflammatory responses. This study aimed to investigate the specific functions and mechanisms of A2aR in neuroinflammation. The findings revealed that A2aR initially exerted a proinflammatory role in the CCH model, transitioning to an anti-inflammatory role in later stages by regulating the phenotypic transformation of microglia. Further analyses using coimmunoprecipitation couple with mass spectrometry, in situ proximity ligation assay, AlphaFold protein structure prediction, [35S]GTPγS binding assay, and NanoBiT technology demonstrated that A2aR formed heteromers with mGluR5 during the early stage of CCH under high glutamate conditions, promoting the polarization of microglia toward...

Humans and nonhumans alike often make choices to gain information, even when the information cannot be used to change the outcome. Prior research has shown that the anterior cingulate cortex (ACC) is important for evaluating options involving reward-predictive information. Here we studied the role of ACC in information choices using optical inhibition to evaluate the contribution of this region during specific epochs of decision-making. Rats could choose between an uninformative option followed by a cue that predicted reward 50% of the time versus a fully informative option that signaled outcomes with certainty but was rewarded only 20% of the time. Reward seeking during the informative S+ cue decreased following ACC inhibition, indicating a causal contribution of this region in supporting reward expectation to a cue signaling reward with certainty. Separately in a positive control experiment and in support of a known role for this region in sustaining high-effort behavior for preferred rewards, we observe...

Vestibular research is essential for understanding and treating disorders such as vertigo and Meniere's disease. The vestibulo-ocular reflex (VOR) is a key method for assessing vestibular function and an essential tool for diagnosing vertigo. Traditionally, the VOR comprises angular VOR (aVOR) and translational VOR (tVOR), which originate from the vestibular semicircular canals (SCCs) and otolith organs, respectively. VOR consists of both fast-phase and slow-phase eye movements, which functionally interact to contribute to gaze control. However, to calculate the gain and phase parameters of the VOR, it is common practice to exclude fast-phase information superimposed on slow-phase eye movements. As a result, the information contained in the fast phase has not been fully utilized. OVAR is primarily used to evaluate otolith function, as there is no SCC input during its steady state. It is widely accepted that fast-phase nystagmus (FPN) during OVAR is generated by periodic otolith inputs via the central vesti...

Early psychosis (EP) is a critical period for psychotic disorders during which the brain undergoes rapid and significant functional and structural changes ( [Shinn et al., 2017][1]). The Human Connectome Project (HCP) is a global effort to map the human brain's connectivity in health and disease. Here we focus on HCP-EP subjects (i.e., those within 5 years of the initial psychotic episode) to determine macro- and microstructural alterations in EP (HCP-EP sample, n  = 179: EP, n  = 123, controls, n  = 56) and their association with clinical outcomes (i.e., symptoms severity) in HCP-EP. We carried out analyses of deformation-based morphometry (DBM), scalar indices from the diffusion tensor imaging (DTI), and tract-based spatial statistics (TBSS). Lastly, we conducted correlation analyses focused on the midbrain (DBM and DTI) to examine associations between its structure and clinical symptoms. Our results show that the midbrain displays robust alteration in its structure (DBM and DTI) in the voxel-based analy...

Human brain banks are essential for studying a wide variety of neurological and neurodegenerative diseases, yet the variability in postmortem interval (PMI)—the time from death to tissue preservation—poses significant challenges due to rapid cellular decomposition, protein alterations, and RNA degradation. Furthermore, the postmortem transcriptomic alterations occurring within distinct cell types are poorly understood. In this study, we analyzed the effect of a 3 h postmortem interval on single-nucleus RNA signatures in the brains of wild-type (WT) and PS19 mice, a common model of tauopathy. We observed that basic quality control metrics (such as the number of genes and reads per cell), total nuclei counts, and RNA integrity number (RINe) remained consistent across all samples, regardless of PMI or genotype. However, a 3 h PMI diminished the number of genes differentially expressed between PS19 and WT mice, suggesting an impact of delayed processing on the detection of disease-specific transcriptomic signa...

Electrophysiology recordings from the brain using laminar multielectrode arrays allow researchers to measure the activity of many neurons simultaneously. However, laminar microelectrode arrays move relative to their surrounding neural tissue for a variety of reasons, such as pulsation, changes in intracranial pressure, and decompression of neural tissue after insertion. Inferring and correcting for this motion stabilizes the recording and is critical to identify and track single neurons across time. Such motion correction is a preprocessing step of standard spike-sorting methods. However, estimating motion robustly and accurately in electrophysiology recordings is challenging due to the stochasticity of the neural data. To tackle this problem, we introduce MEDiCINe ( M otion E stimation by Di stributional C ontrastive I nference for Ne urophysiology), a novel motion estimation method. We show that MEDiCINe outperforms existing motion estimation methods on an extensive suite of simulated neurophysiology rec...

Mitral cells (MCs) and tufted cells (TCs) in the olfactory bulb (OB) act as an input convergence hub and transmit information to higher olfactory areas. Since first characterized, they have been classed as distinct projection neurons based on size and location: laminarly arranged MCs with a diameter larger than 20 µm in the mitral layer (ML) and smaller TCs spread across both the ML and external plexiform layers (EPL). Recent in vivo work has shown that these neurons encode complementary olfactory information, akin to parallel channels in other sensory systems. Yet, many ex vivo studies still collapse them into a single class, mitral/tufted, when describing their physiological properties and impact on circuit function. Using immunohistochemistry and whole-cell patch–clamp electrophysiology in fixed or acute slices from adult mice, we attempted to align in vivo and ex vivo data and test a soma size-based classifier of bulbar projection neurons using passive and intrinsic firing properties. We found that the...

How humans achieve such a high degree of prosocial behavior is a subject of considerable interest. Exploration of the neural foundations of human prosociality has garnered significant attention in recent decades. Nevertheless, the neural mechanisms underlying human prosociality remain to be elucidated. To address this knowledge gap, we analyzed multimodal brain imaging data and data from 15 economic games. The results revealed several significant associations between brain characteristics and prosocial behavior, including stronger interhemispheric connectivity and larger corpus callosum volume. Greater functional segregation and integration, alongside fewer myelin maps combined with a thicker cortex, were linked to prosocial behavior, particularly within the social brain regions. The current study demonstrates that these metrics serve as brain markers of human prosocial behavior and provides novel insights into the structural and functional brain basis of human prosocial behavior.

This is a playlist of 19 videos from the 2016 FENS-Hertie Winter School. Since the groundbreaking description of patient H.M. in the 1950's, our understanding of human memory and the mechanisms underlying memory functions has increased dramatically in the last decades. Through extensive interactions with leaders in the field, the 2016 FENS-Hertie Winter School provided a comprehensive overview of both the basic and the latest knowledge about memory functions and their underlying mechanisms in humans.

Emery Brown, professor of anesthesia at Harvard Medical School, discusses his career trajectory as a physician-scientist and his work-life balance. He delivered this talk during SfN’s Meet-the-Expert Series at Neuroscience 2017. The text below has been condensed and lightly edited and offer highlights from his talk. Listen to the audio recording above for the full remarks. Transitioning From Romance Languages to Circadian Rhythms I started out as an undergraduate at Harvard, majoring in romance languages. I knew I was going to go to medical school. I figured I would work for the World Health Organization, traveling around the world and stamping out diseases. However, in my sophomore year, my roommates concentrated in economics, and they talked like they understood the world. I then switched into economics, and in my junior year, I switched my major to applied mathematics. I also did an undergraduate thesis, and I wrote about studying outcomes from high-risk surgery. It was funded by the anesthesiology department at Massachusetts General Hospital. I didn't solve an earth-shattering problem, but it taught me how to formulate a problem, research it, and write it up.