Temporal lobe epilepsy is common, but mechanisms of seizure initiation are unclear. We evaluated seizure initiation in female and male rats that had been systemically treated with pilocarpine, a widely used model of temporal lobe epilepsy. Local field potential recordings from many brain regions revealed variable sites of earliest recorded seizure activity, but mostly the ventral hippocampal formation. To test whether inactivation of the ventral hippocampal formation would reduce seizures, mini-osmotic pumps were used to continually and focally deliver tetrodotoxin. High doses of tetrodotoxin infused unilaterally into the ventral hippocampal formation blocked seizures reversibly but also reduced local field potential amplitudes in remote brain regions, indicating distant effects. A lower dose did not reduce local field potential amplitudes in remote brain regions but did not reduce seizures when infused unilaterally. Instead, seizures tended to initiate in the contralateral ventral hippocampal formation. B...

Tactile sensations can bias visual perception in the awake state while visual sensitivity is known to be facilitated by sleep. It remains unknown, however, whether the tactile sensation during sleep can bias the visual improvement after sleep. Here, we performed nap experiments in human participants (n = 56, 18 males, 38 females) to demonstrate that repetitive tactile motion stimulation on the fingertip during slow wave sleep selectively enhanced subsequent visual motion detection. The visual improvement was associated with slow wave activity. The high activation at the high beta frequency was found in the occipital electrodes after the tactile motion stimulation during sleep, indicating a visual-tactile cross-modal interaction during sleep. Furthermore, a second experiment (n = 14, 14 females) to examine whether a hand- or head-centered coordination is dominant for the interpretation of tactile motion direction showed that the biasing effect on visual improvement occurs according to the hand-centered coor...

Purkinje cells (PCs) are spontaneously active neurons of the cerebellar cortex that inhibit glutamatergic projection neurons within the deep cerebellar nuclei (DCN) that provide the primary cerebellar output. Brief reductions of PC firing rapidly increase DCN neuron firing. However, prolonged reductions of PC inhibition, as seen in some disease states, certain types of transgenic mice, during optogenetic suppression of PC firing, and in acute slices of the cerebellum, do not lead to large sustained increases in DCN firing. Here we test whether DCN neurons undergo spike-frequency adaptation that could account for these properties. We perform current-clamp recordings at near physiological temperature in acute brain slices from mice of both sexes to examine how DCN neurons respond to prolonged depolarizations. DCN neuron adaptation is exceptionally slow and bidirectional. A depolarizing current step evokes large initial increases in firing that decay to less than 20% of the initial increase within approximate...

Though the neural basis of working memory (WM) capacity is often studied by exploiting inter-individual differences, capacity may also differ across memory materials within a given individual. Here, we exploit the content-dependence of WM capacity as a novel approach to investigate the oscillatory correlates of WM capacity, focusing on posterior 9-12 Hz alpha activity during retention. We recorded scalp electroencephalography (EEG) while male and female human participants performed WM tasks with varying memory loads (2 vs. 4 items) and materials (English letters vs. regular shapes vs. abstract shapes). First, behavioural data confirmed that memory capacity was fundamentally content-dependent: capacity for abstract shapes plateaued at around two, while the participants could remember more letters and regular shapes. Critically, content-specific capacity was paralleled in the degree of attenuation of EEG-alpha activity that plateaued in a similar, content-specific, manner. While we observed greater alpha att...

Behavioral interactions with moving objects are challenged by response latencies within the sensory and motor nervous systems. In vision, the combined latency from phototransduction and synaptic transmission from the retina to central visual areas amounts to 50-100 ms, depending on stimulus conditions. Time required for generating appropriate motor output adds to this latency and further compounds the behavioral delay. Neuronal adaptations that help counter sensory latency within the retina have been demonstrated in some species, but how general these specializations are, and where in the circuitry they originate, remains unclear. To address this, we studied the timing of object motion-evoked responses at multiple signaling stages within the mouse retina using two-photon fluorescence calcium and glutamate imaging, targeted whole-cell electrophysiology, and computational modeling. We found that both ON and OFF-type ganglion cells, as well as the bipolar cells that innervate them, temporally advance the posi...

Accumulating evidence indicates significant consequences for astrocytes associated with drug abuse. For example, reductions in structural features and synaptic colocalization of male rat nucleus accumbens (NAc) astrocytes are observed following short-access (ShA, 2 hours/day) self-administration and extinction from cocaine, methamphetamine, and heroin. However, it is unknown whether these observations extend to other rodent models of drug abuse, how enduring these effects may be, and whether similar effects are observed in female rats. Here we assess the effects of long-access (LgA, 6 hours/day) cocaine self-administration and abstinence on NAc astrocytes separately in male and female rats, employing a commonly used behavioral approach to investigate the incubation of cocaine craving. NAc astrocytes from male rats exhibit extensive (∼40%) reductions in surface area, volume, and postsynaptic colocalization 45 days, but not 24 hours after the last self-administration session. In contrast, no effect of self-a...

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...