Task representations are critical for cognitive control and adaptive behavior. The hierarchical organization of task representations allows humans to maintain goals, integrate information across varying contexts, and select potential responses. In this study we characterized the structure and interactive dynamics of task representations that facilitate cognitive control. Human participants (both males and females) performed a hierarchical task that required them to select a response rule while considering the contingencies from different contextual inputs. By applying time- and frequency-resolved representational similarity analysis to human electroencephalography data, we characterized properties of task representations that are otherwise difficult to observe. We found that participants formed multiple representations of task-relevant contexts and features from the presented stimuli, beyond simple stimulus-response mappings. These disparate representations were hierarchically structured, with higher-order...

Traumatic brain injury (TBI) triggers a plethora of inflammatory events in the brain that aggravate secondary injury and impede tissue repair. Resident microglia (Mi) and blood-borne infiltrating macrophages (MΦ) are major players of inflammatory responses in the post-TBI brain and possess high functional heterogeneity. However, the plasticity of these cells has yet to be exploited to develop therapies that can mitigate brain inflammation and improve the outcome after TBI. This study investigated the transcription factor STAT1 as a key determinant of proinflammatory Mi/MΦ responses and aimed to develop STAT1 as a novel therapeutic target for TBI using a controlled cortical impact model of TBI on adult male mice. TBI induced robust upregulation of STAT1 in the brain at the subacute injury stage, which occurred primarily in Mi/MΦ. Intraperitoneal administration of fludarabine, a selective STAT1 inhibitor, markedly alleviated proinflammatory Mi/MΦ responses and brain inflammation burden after TBI. Such phenot...

The functional magnetic resonance imaging under naturalistic paradigm (NfMRI) showed great advantages in identifying complex and interactive functional brain networks due to its dynamics and multimodal information. In recent years, various deep learning models, such as deep convolutional autoencoder (DCAE), deep belief network (DBN) and volumetric sparse deep belief network (vsDBN), can obtain hierarchical functional brain networks (FBN) and temporal features from fMRI data. Among them, the vsDBN model revealed a good capability in identifying hierarchical FBNs by modelling fMRI volume images. However, due to the high dimensionality of fMRI volumes and the diverse training parameters of deep learning methods, especially the network architecture that is the most critical parameter for uncovering the hierarchical organization of human brain function, researchers still face challenges in designing an appropriate deep learning framework with automatic network architecture optimization to model volumetric NfMRI...

Neural responses of V7 and LOC have been shown to correlate with changes in behavioural metrics of depth-sensitivity observed as a function of object-context, although it is unclear as to whether the behavioural manifestation results from an alteration of early depth-specific responses in V7 or arise a result of alterations of object-level representations at LOC that subsequently feedback to affecting disparity readouts in dorsal cortex. Here, we used online transcranial magnetic stimulation to examine the roles of these two areas in giving rise to context-disparity interactions. Stimuli were disparity-defined geometric objects rendered as random-dot stereograms, presented in geometrically plausible and implausible variations. Observers’ sensitivity to depth (depth discrimination) or object identity (plausibility discrimination) was indexed whilst receiving rTMS at one of the two sites of interest (V7, LOC) along with a control site (Cz). TMS over LOC produced results no different from TMS over baseline Cz...

Fragile X Syndrome (FXS) is a leading monogenic cause of intellectual disability and autism spectrum disorders, spurring decades of intense research and a multitude of mouse models. So far, these models do not recapitulate the genetic underpinning of classical FXS - CGG repeat-induced methylation of the Fmr1 locus - and their findings have failed to translate into the clinic. We sought to answer whether this disparity was due to low repeat length and generated a novel mouse line with 341 repeats, Fmr1hs341 , which is the largest allele in mice reported to date. This repeat length is significantly longer than the 200 repeats generally required for methylation of the repeat tract and promoter region in FXS patients, which leads to silencing of the FMR1 gene. Bisulfite sequencing fails to detect the robust methylation expected of FXS in Fmr1hs341 mice. qRT-PCR and Western blotting results also do not resemble FXS, and instead produce a biochemical profile consistent with the Fragile X-associated premutation d...

Two key features endow Drosophila Dscam1 with the potential to provide a ubiquitous code for neuronal arbor self-avoidance. First, Dscam1 contains three large cassettes of alternative exons, so that stochastic alternative splicing yields 19,008 Dscam1 isoforms with different Ig ectodomains. Second, each neuron expresses a different subset of Dscam1 isoforms, and isoform-specific homophilic binding causes repulsion. This results in even spacing of self-arbors, while processes of other neurons can intermingle and share the same synaptic partners. In principle, this Dscam1 code could ensure arbor spacing of all neurons in Drosophila. This model is strongly supported by studies on dendrite spacing in the peripheral nervous system and studies on axonal branch segregation during brain development. However, the situation is less clear for central neuron dendrites, the major substrate for synaptic input in the CNS. We systematically tested the role of Dscam1 for dendrite growth and spacing in 8 different types of ...

Visual neural plasticity and V1 saliency detection are vital for efficient coding of dynamically changing visual inputs. However, how does neural plasticity contribute to saliency detection of temporal statistically distributed visual stream remains unclear. Therefore, we adopted randomly presented but unevenly distributed stimuli with multiple orientations and examined the single-unit responses evoked by this biased orientation-adaptation protocol by single-unit recordings in the visual thalamo–ventral pathway of cats (of either sex). We found neuronal responses potentiated when the probability of biased orientation was slightly higher than other nonbiased ones and suppressed when the probability became much higher. This single neuronal short-term bidirectional plasticity is selectively induced by optimal stimuli but is interocularly transferable. It is inducible in LGN, Area 17, and Area 21a with distinct and hierarchically progressive patterns. With the results of latency analysis, receptive field struc...

To efficiently process information, the brain shifts between encoding and retrieval states, prioritizing bottom-up or top-down processing accordingly. Expectation violation before or during learning has been shown to trigger an adaptive encoding mechanism, resulting in better memory for unexpected events. Using fMRI, we explored (1) whether this encoding mechanism is also triggered during retrieval, and if so, (2) what the temporal dynamics of its mnemonic consequences are. Male and female participants studied object images, then, with new objects, they learned a contingency between a cue and a semantic category. Rule-abiding (expected) and violating (unexpected) targets and similar foils were used at test. We found interactions between previous and current similar events' expectation, such that when an expected event followed a similar but unexpected event, its performance was boosted, underpinned by activation in the hippocampus, midbrain, and occipital cortex. In contrast, a sequence of two unexpected s...

It is a commonly accepted view that light stimulation of mammalian photoreceptors causes a graded change in membrane potential instead of developing a spike. The presynaptic Ca2+ channels serve as a crucial link for the coding of membrane potential variations into neurotransmitter release. Cav1.4 L-type Ca2+ channels are expressed in photoreceptor terminals, but the complete pool of Ca2+ channels in cone photoreceptors appears to be more diverse. Here, we discovered, employing whole-cell patch-clamp recording from cone photoreceptor terminals in both sexes of mice, that their Ca2+ currents are composed of low- (T-type Ca2+ channels) and high- (L-type Ca2+ channels) voltage-activated components. Furthermore, Ca2+ channels exerted self-generated spike behavior in dark membrane potentials, and spikes were generated in response to light/dark transition. The application of fast and slow Ca2+ chelators revealed that T-type Ca2+ channels are located close to the release machinery. Furthermore, capacitance measure...