Natural scenes deliver rich sensory information about the world. Decades of research has shown that the scene-selective network in the visual cortex represents various aspects of scenes. However, less is known about how such complex scene information is processed beyond the visual cortex, such as in the prefrontal cortex. It is also unknown how task context impacts the process of scene perception, modulating which scene content is represented in the brain. In this study, we investigate these questions using scene images from four natural scene categories, which also depict two types of scene attributes, temperature (warm or cold), and sound level (noisy or quiet). A group of healthy human subjects from both sexes participated in the present study using fMRI. In the study, participants viewed scene images under two different task conditions; temperature judgment and sound-level judgment. We analyzed how these scene attributes and categories are represented across the brain under these task conditions. Our f...

Maintaining and manipulating sequences online is essential for daily activities such as scheduling a day. In Parkinson’s disease (PD), sequential working memory deficits have been associated with altered regional activation and functional connectivity in the basal ganglia. This study demonstrates that the substantia nigra (SN) integrity correlated with basal ganglia function and sequencing performance in 29 patients with PD (17 women) and 29 healthy controls (HC, 18 women). In neuromelanin-sensitive structural MRI, PD patients showed smaller SN than HC. In a digit ordering task with functional MRI, participants either recalled sequential digits in the original order (‘pure recall’) or rearranged the digits and recalled the new sequence (‘reorder & recall’). PD patients performed less accurately than HC, accompanied by the caudate and pallidal hypo-activation, subthalamic hyper-activation, and weakened functional connectivity between the bilateral SN and all three basal ganglia regions. PD patients with lar...

The sense of balance relies on vestibular hair cells, which detect head motions. Mammals have two types of vestibular hair cell, I and II, with unique morphological, molecular, and physiological properties. Furthermore, each hair cell type synapses on a unique form of afferent nerve terminal. Little is known about the mechanisms in mature animals that maintain the specific features of each hair cell type or its post-synaptic innervation. We found that deletion of the transcription factor Sox2 from type II hair cells in adult mice of both sexes caused many cells in utricles to acquire features unique to type I hair cells and to lose type II-specific features. This cellular transdifferentiation, which included changes in nuclear size, chromatin condensation, soma and stereocilium morphology, and marker expression, resulted in a significantly higher proportion of type I-like hair cells in all epithelial zones. Furthermore, Sox2 deletion from type II hair cells triggered non-cell autonomous changes in vestibul...

The development, persistence and relapse of drug addiction require drug memory that generally develops with drug administration-paired contextual stimuli. Adult hippocampal neurogenesis (AHN) contributes to cocaine memory formation; however, the underlying mechanism remains unclear. Male mice hippocampal expression of Tau was significantly decreased during the cocaine-associated memory formation. Genetic overexpression of four microtubule-binding repeats Tau (4R Tau) in the mice hippocampus disrupted cocaine memory by suppressing AHN. Furthermore, 4R Tau directly interacted with phosphoinositide 3-kinase (PI3K)-p85 and impaired its nuclear translocation and PI3K-AKT signaling, processes required for hippocampal neuron proliferation. Collectively, 4R Tau modulates cocaine memory formation by disrupting AHN, suggesting a novel mechanism underlying cocaine memory formation and provide a new strategy for the treatment of cocaine addiction. SIGNIFICANCE Drug memory that generally develops with drug-paired co...

Intrauterine growth restriction (IUGR) and oxygen exposure in isolation and combination adversely affect the developing brain, putting infants at risk for neurodevelopmental disability including cerebral palsy. Rodent models of IUGR and postnatal hyperoxia have demonstrated oligodendroglial injury with subsequent white matter injury (WMI) and motor dysfunction. Here we investigate transcriptomic dysregulation in IUGR with and without hyperoxia exposure to account for the abnormal brain structure and function previously documented. We performed RNA sequencing and analysis using a mouse model of IUGR and found that IUGR, hyperoxia, and the combination of IUGR with hyperoxia (IUGR/hyperoxia) produced distinct changes in gene expression. IUGR in isolation demonstrated the fewest differentially expressed genes compared to control. In contrast, we detected several gene alterations in IUGR/hyperoxia; genes involved in myelination were strikingly downregulated. We also identified changes to specific regulators inc...

The map of category-selectivity in human ventral temporal cortex (VTC) provides organizational constraints to models of object recognition. One important principle is lateral-medial response biases to stimuli that are typically viewed in the center or periphery of the visual field. However, little is known about the relative temporal dynamics and location of regions that respond preferentially to stimulus classes that are centrally viewed, like the face- and word-processing networks. Here, word- and face-selective regions within VTC were mapped using intracranial recordings from 36 patients. Partially overlapping, but also anatomically dissociable patches of face- and word-selectivity were found in VTC. In addition to canonical word-selective regions along the left posterior occipitotemporal sulcus, selectivity was also located medial and anterior to face-selective regions on the fusiform gyrus at the group level and within individual male and female subjects. These regions were replicated using 7 Tesla fM...

The Xenopus laevis experimental system has provided significant insight into the development and plasticity of neural circuits. Xenopus neuroscience research would be enhanced by additional tools to study neural circuit structure and function. Rabies viruses are powerful tools to label and manipulate neural circuits and have been widely used to study mesoscale connectomics. Whether rabies virus can be used to transduce neurons and express transgenes in Xenopus has not been systematically investigated. Glycoprotein-deleted rabies virus transduces neurons at the axon terminal and retrogradely labels their cell bodies. We show that glycoprotein-deleted rabies virus infects local and projection neurons in the Xenopus tadpole when directly injected into brain tissue. Pseudotyping glycoprotein-deleted rabies with EnvA restricts infection to cells with exogenous expression of the EnvA receptor, TVA. EnvA pseudotyped virus specifically infects tadpole neurons with promoter-driven expression of TVA, demonstrating i...

Dopamine replacement by levodopa is the most widely used therapy for Parkinson’s disease (PD), however patients often develop side effects, known as levodopa-induced dyskinesia (LID), that usually need therapeutic intervention. There are no suitable therapeutic options for LID, except for the use of the NMDA receptor antagonist amantadine, which has limited efficacy. The NMDA receptor is indeed the most plausible target to manage LID in PD and recently the kinase Fyn- one of its key regulators- became a new putative molecular target involved in LID. The aim of this work was to reduce Fyn expression to alleviate LID in a mouse model of PD. We performed intra-striatal delivery of a designed micro-RNA against Fyn (miRNA-Fyn) in 6-OHDA-lesioned mice treated with levodopa. The miRNA-Fyn was delivered either before or after levodopa exposure to assess its ability to prevent or revert dyskinesia. Pre-administration of miRNA-Fyn reduced LID with a concomitant reduction of FosB-ΔFosB protein levels –a marker of LID...

Cortical pyramidal neurons possess a persistent Na+ current (INaP) which, in contrast to the larger transient current, does not undergo rapid inactivation. Although relatively quite small, INaP is active at subthreshold voltages and therefore plays an important role in neuronal input-output processing. The subcellular distribution of channels responsible for INaP and the mechanisms which render them persistent are not known. Using high-speed fluorescence Na+ imaging and whole-cell recordings in brain slices obtained from mice of either sex, we reconstructed the INaP elicited by slow voltage ramps in soma and processes of cortical pyramidal neurons. We found that in all neuronal compartments, the relationship between persistent Na+ conductance and membrane voltage has the shape of a Boltzmann function. Although the density of channels underlying INaP was about twofold lower in the axon initial segment (AIS) than in the soma, the axonal channels were activated by about 10 mV less depolarization than were som...

In sensory systems of the brain, mechanisms exist to extract distinct features from stimuli to generate a variety of behavioural repertoires. These often correspond to different cell types at various stages in sensory processing. In the mammalian olfactory system, complex information processing starts in the olfactory bulb, whose output is conveyed by mitral and tufted cells (MCs and TCs). Despite many differences between them, and despite the crucial position they occupy in the information hierarchy, Cre-driver lines that distinguish them do not yet exist. Here, we sought to identify genes that are differentially expressed between MCs and TCs of the mouse, with an ultimate goal to generate a cell-type specific Cre-driver line, starting from a transcriptome analysis using a large and publicly available single-cell RNA-seq dataset (Zeisel et al., 2018). Many genes were differentially expressed, but only a few showed consistent expressions in MCs and at the specificity required. After further validating thes...