Coordinating the four limbs is an important feature of terrestrial mammalian locomotion. When the foot dorsum contacts an obstacle, cutaneous mechanoreceptors send afferent signals to the spinal cord to elicit coordinated reflex responses in the four limbs to ensure dynamic balance and forward progression. To determine how the locomotor pattern of all four limbs changes in response to a sensory perturbation evoked by activating cutaneous afferents from one hindlimb, we electrically stimulated the superficial peroneal (SP) nerve with a relatively long train at four different phases (mid-stance, stance-to-swing transition, mid-swing, and swing-to-stance transition) of the hindlimb cycle in seven adult cats. The largest functional effects of the stimulation were found at mid-swing and at the stance-to-swing transition with several changes in the ipsilateral hindlimb, such as increased activity in muscles that flex the knee and hip joints, increased joint flexion and toe height, increased stride/step lengths a...

The importance of action–perception loops necessitates efficient computations linking motor and sensory systems. Corollary discharge (CD), a concept in motor-to-sensory transformation, has been proposed to predict the sensory consequences of actions for efficient motor and cognitive control. The predictive computation has been assumed to realize via inhibiting sensory reafference when actions are executed. Continuous control throughout the course of action demands inhibitory function ubiquitously on all potential reafference when sensory consequences are not available before execution. However, the temporal and functional characteristics of CD are unclear. When does CD begin to operate? To what extent does CD inhibit sensory processes? How is the inhibitory function implemented in neural computation? Using a delayed articulation paradigm with three types of auditory probes (speech, nonspeech, and nonhuman sounds) in an electroencephalography experiment with 20 human participants (7 males), we found that pr...

Hyperactivation of cyclin-dependent kinase 5 (Cdk5) by p25, contributes to neuroinflammation causing neurodegeneration in Parkinson’s disease (PD) and Alzheimer’s disease. However, the mechanism by which Cdk5 induces neuroinflammation in the PD brain is largely unexplored. Here, we show that Cdk5 phosphorylates cytosolic phospholipase A2 (cPLA2) at Thr-268 and Ser-505 sites lead to its activation and generation of eicosanoid products. Mutational studies using site-directed mutagenesis and molecular simulations show that the architecture of the protein changes on each single-point mutation. Interestingly, double mutations also led to a severe decline in the activity of cPLA2 and to the disruption of its translocation to the plasma membrane. Further, the brain lysates of transgenic PD mouse models show hyperactivation of Cdk5, resulting in enhanced phosphorylation of Thr-268 and Ser-505 of cPLA2 and its heightened activity, confirming the findings observed in the cell culture model of PD. These phosphorylati...

Understanding how the brain functions differently as one learns to read may shed light on the controversial nature of the reading ability of human being. Logographic writing system such as Chinese has been found to rely on specialized neural substrates beyond the reading network of alphabetic languages. The ability to read in Chinese has also been proposed to rely on writing skills. However, it was unclear whether the learning-related alteration of neural responses was language specific or resulted from the more reliance on writing practice during acquisition. This study investigated whether the emergence of typical logographic-specific regions relied on learning by writing. We taught proficient alphabetic language readers Chinese characters and used pre-test and post-test to identify changes in two critical stages of reading, namely, orthographic processing and orthographic-to-phonological mapping. Two typical left hemispheric areas for logographic reading showed increased responses to characters in the b...

Visual accuracy is consistently shown to be modulated around the time of the action execution. The neural underpinning of this motor-induced modulation of visual perception is still unclear. Here, we investigate with EEG whether it is related to the readiness potential, an event-related potential (ERP) linked to motor preparation. Across 18 human participants, the magnitude of visual modulation following a voluntary button press was found to correlate with the readiness potential amplitude measured during visual discrimination. Participants’ amplitude of the readiness potential in a purely motor-task was also found to correlate with the extent of the motor-induced modulation of visual perception in the visuomotor task. These results provide strong evidence that perceptual changes close to action execution are associated with motor preparation processes and that this mechanism is independent of task contingencies. Further, our findings suggest that the readiness potential provides a fingerprint of individua...

Temporal reward discounting describes the decrease of value of a reward as a function of delay. Decision-making between future aversive outcomes is much less studied, and there is no clear decision pattern across studies; while some authors suggest that human and nonhuman animals prefer sooner over later painful shocks, others found the exact opposite. In a series of three experiments, Long–Evans rats chose between differently timed electric shocks and rewards in a T-maze. In experiment 1, rats chose between early and late painful shocks with identical, long reward delays; in experiment 2, they chose between early reward and early shocks, or late rewards and late shocks; in experiment 3, they chose between early and late rewards, with identical, short delays to the shock. We tested the predictions of two competing hypotheses: the aversive discounting theory assumes that future shocks are discounted, and, hence, less unpleasant than early shocks. The utility from anticipation theory implies that rats derive...

Absence of presynaptic protein MUNC18-1 (gene: Stxbp1 ) leads to neuronal cell death at an immature stage before synapse formation. Here, we performed transcriptomic and proteomic profiling of immature Stxbp1 knock-out (KO) cells to discover which cellular processes depend on MUNC18-1. Hippocampi of Stxbp1 KO mice showed cell type-specific dysregulation of 2123 transcripts primarily related to synaptic transmission and immune response. To further investigate direct, neuron-specific effects of MUNC18-1 depletion, a proteomic screen was performed on murine neuronal cultures at two developmental timepoints before onset of neuron degeneration. 399 proteins were differentially expressed, which were primarily involved in synaptic function (especially synaptic vesicle exocytosis) and neuron development. We further show that many of the downregulated proteins on loss of MUNC18-1 are normally upregulated during this developmental stage. Thus, absence of MUNC18-1 extensively dysregulates the transcriptome and proteo...

Successful retrieval of a specific item from visual working memory (VWM) depends on the binding of that item to its unique context. Recent functional magnetic resonance imaging studies of VWM manipulating memory set homogeneity have identified an important role for the intraparietal sulcus in context binding, independent of any role in representing stimulus identity. The current study explored whether the contralateral delay activity (CDA), which is an event-related potential (ERP) component derived from posterior electrodes that tracks the amount of information held in VWM, might also be sensitive to context-binding demands. In experiment 1, human participants performed lateralized delayed recognition with memory sets containing one, three, or five items that were drawn from the same category (orientations: “homogeneous”) or from different categories (orientation, color, and luminance: “heterogeneous”). Because the location and identity of the memory probe indicated the item to be retrieved, homogeneous t...

Navigating through an environment requires knowledge about one’s direction of self-motion (heading) and traveled distance. Behavioral studies showed that human participants can actively reproduce a previously observed travel distance purely based on visual information. Here, we employed electroencephalography (EEG) to investigate the underlying neural processes. We measured, in human observers, event-related potentials (ERPs) during visually simulated straight-forward self-motion across a ground plane. The participants’ task was to reproduce (active condition) double the distance of a previously seen self-displacement (passive condition) using a gamepad. We recorded the trajectories of self-motion during the active condition and played it back to the participants in a third set of trials (replay condition). We analyzed EEG activity separately for four electrode clusters: frontal (F), central (C), parietal (P), and occipital (O). When aligned to self-motion onset or offset, response modulation of the ERPs w...

Mice are opportunistic omnivores that readily learn to hunt and eat insects such as crickets. The details of how mice learn these behaviors and how these behaviors may differ in strains with altered neuroplasticity are unclear. We quantified the behavior of juvenile wild-type (WT) and Shank3 knock-out (KO) mice as they learned to hunt crickets during the critical period for ocular dominance plasticity. This stage involves heightened cortical plasticity including homeostatic synaptic scaling, which requires Shank3, a glutamatergic synaptic protein that, when mutated, produces Phelan-McDermid syndrome and is often comorbid with autism spectrum disorder (ASD). Both strains showed interest in examining live and dead crickets and learned to hunt. Shank3 knock-out mice took longer to become proficient, and, after 5 d, did not achieve the efficiency of wild-type mice in either time-to-capture or distance-to-capture. Shank3 knock-out mice also exhibited different characteristics when pursuing crickets that could n...