Multifaceted microglial functions in the developing brain, such as promoting the differentiation of neural progenitors and contributing to the positioning and survival of neurons, have been progressively revealed. Although previous studies have noted the relationship between vascular endothelial cells and microglia in the developing brain, little attention has been given to the importance of pericytes, the mural cells surrounding endothelial cells. In this study, we attempted to dissect the role of pericytes in microglial distribution and function in developing mouse brains. Our immunohistochemical analysis showed that approximately half of the microglia attached to capillaries in the cerebral walls. Notably, a magnified observation of the position of microglia, vascular endothelial cells and pericytes demonstrated that microglia were preferentially associated with pericytes that covered 79.8% of the total capillary surface area. Through in vivo pericyte depletion induced by the intraventricular administra...

Extensive research has shown that perceptual information of faces is processed in a network of hierarchically-organized areas within ventral temporal cortex. For familiar and famous faces, perceptual processing of faces is normally accompanied by extraction of semantic knowledge about the social status of persons. Semantic processing of familiar faces could entail progressive stages of information abstraction. However, the cortical mechanisms supporting multistage processing of familiar faces have not been characterized. Here, using an event-related fMRI experiment, familiar faces from four celebrity groups (actors, singers, politicians, and football players) and unfamiliar faces were presented to the human subjects (both males and females) while they were engaged in a face categorization task. We systematically explored the cortical representations for faces, familiar faces, subcategories of familiar faces, and familiar face identities using whole-brain univariate analysis, searchlight-based multivariate ...

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 dCA3. In contrast, dCA1 rotates more in concert with the global cues. In addition, pCA1 and dCA1 display comparable leve...

It has been proposed that the auditory cortex in the deaf humans might undergo task-specific reorganization. However, evidence remains scarce as previous experiments used only two very specific tasks (temporal processing and face perception) in visual modality. Here, congenitally deaf/hard of hearing and hearing women and men were enrolled in an fMRI experiment as we sought to fill this evidence gap in two ways. First, we compared activation evoked by a temporal processing task performed in two different modalities, visual and tactile. Second, we contrasted this task with a perceptually similar task that focuses on the spatial dimension. Additional control conditions consisted of passive stimulus observation. In line with the task specificity hypothesis, the auditory cortex in the deaf was activated by temporal processing in both visual and tactile modalities. This effect was selective for temporal processing relative to spatial discrimination. However, spatial processing also led to significant auditory c...

The subgenual (sgACC) and perigenual (pgACC) anterior cingulate are important afferents of the amygdala, with different cytoarchitecture, connectivity, and function. The sgACC is associated with arousal mechanisms linked to salient cues, whereas the pgACC is engaged in conflict decision-making, including in social contexts. After placing same-size, small volume tracer injections into sgACC and pgACC of the same hemisphere in male macaques, we examined anterogradely labeled fiber distribution to understand how these different functional systems communicate in the main amygdala nuclei at both mesocopic and cellular levels. The sgACC has broad-based termination patterns. In contrast, the pgACC has a more restricted pattern, which was always nested in sgACC terminals. Terminal overlap occurred in subregions of the accessory basal and basal nuclei, which we termed “hotspots.” In triple-labeling confocal studies, the majority of randomly selected CaMKIIα-positive cells (putative amygdala glutamatergic neurons) i...

Martin Field, Istvan P. Lukacs, Emily Hunter, Richard Stacey, Puneet Plaha, et al. (see pages [9702–9719][1]) GABA acts on extrasynaptic GABAA receptors (GABAARs) to produce tonic currents in many neurons in the brain. Such currents contribute to slow oscillations during sleep and mediate the

Kisspeptin (Kiss1) neurons are essential for reproduction, but their role in the control of energy balance and other homeostatic functions remains unclear. High-frequency firing of hypothalamic arcuate Kiss1 (Kiss1ARH) neurons releases kisspeptin into the median eminence, and neurokinin B (NKB) and dynorphin onto neighboring Kiss1ARH neurons to generate a slow EPSP mediated by TRPC5 channels that entrains intermittent, synchronous firing of Kiss1ARH neurons. High-frequency optogenetic stimulation of Kiss1ARH neurons also releases glutamate to excite the anorexigenic proopiomelanocortin (POMC) neurons and inhibit the orexigenic neuropeptide Y/agouti-related peptide (AgRP) neurons via metabotropic glutamate receptors. At the molecular level, the endoplasmic reticulum (ER) calcium-sensing protein stromal interaction molecule 1 (STIM1) is critically involved in the regulation of neuronal Ca2+ signaling and neuronal excitability through its interaction with plasma membrane (PM) calcium (e.g., TRPC) channels. Th...

Tremor, a common and often primary symptom of Parkinson's disease, has been modeled with distinct onset and maintenance dynamics. To identify the neurophysiologic correlates of each state, we acquired intraoperative cortical and subthalamic nucleus recordings from 10 patients (9 male, 1 female) performing a naturalistic visual–motor task. From this task, we isolated short epochs of tremor onset and sustained tremor. Comparing these epochs, we found that the subthalamic nucleus was central to tremor onset, as it drove both motor cortical activity and tremor output. Once tremor became sustained, control of tremor shifted to cortex. At the same time, changes in directed functional connectivity across sensorimotor cortex further distinguished the sustained tremor state. SIGNIFICANCE STATEMENT Tremor is a common symptom of Parkinson's disease (PD). While tremor pathophysiology is thought to involve both basal ganglia and cerebello–thalamic–cortical circuits, it is unknown how these structures functionally inte...

Introduction: The hippocampus is a locus of working memory (WM) with anterior and posterior subregions that differ in their transcriptional and external connectivity patterns. However, the involvement and functional connections between these subregions in WM processing are poorly understood. Methods: To address these issues, we recorded intracranial EEG from the anterior and the posterior hippocampus in human (7 females and 7 males) who maintained a set of letters in their WM. Results: We found that WM maintenance was accompanied by elevated low-frequency activity in both the anterior and posterior hippocampus and by increased theta/alpha band (3-12 Hz) phase synchronization between anterior and posterior subregions. Cross-frequency and Granger prediction analyses consistently showed that the correct WM trials were associated with theta/alpha band-coordinated unidirectional influence from the posterior to the anterior hippocampus. In contrast, WM errors were associated with bidirectional interactions bet...