An accurate assessment of the time course, components, and magnitude of postsynaptic currents is important for a quantitative understanding of synaptic integration and signaling in dendritic spines. These parameters have been studied in some detail in previous experiments, primarily using 2-photon imaging of [Ca2+]i changes and 2-photon uncaging of glutamate. However, even with these revolutionary techniques there are some missing pieces in our current understanding, particularly related to the time courses of synaptically evoked [Ca2+]i and [Na+]i changes. In new experiments we used low affinity, linear Na+ and Ca2+ indicators, laser fluorescence stimulation, and a sensitive camera-based detection system, combined with electrical stimulation and 2-photon glutamate uncaging, to extend measurements of these spine parameters. We found that (a) almost all synaptically activated Na+ currents in CA1 hippocampal pyramidal neuron spines in slices from mice of either sex are through AMPA receptors with little Na+ ...

Human brains are capable of modulating innate activities to adapt to novel environments and tasks; for sensorimotor neural system this means acquisition of a rich repertoire of activity patterns that improve behavioral performance. To directly map the process of acquiring the neural repertoire during tasks onto performance improvement, we analyzed net neural populational activity during the learning of its voluntary modulation by brain-computer interface (BCI) operation in female and male humans. The recorded whole-head high-density scalp electroencephalograms (EEG) were subjected to dimensionality reduction algorithm to capture changes in cortical activity patterns represented by the synchronization of neuronal oscillations during adaptation. Although the preserved variance of targeted features in the reduced dimensions was 20%, we found systematic interactions between the activity patterns and BCI classifiers that detected motor attempt; the neural manifold derived in the embedded space was stretched alo...

Decision-making is an essential cognitive process by which we interact with the external world. However, attempts to understand the neural mechanisms of decision-making are limited by the current available animal models and the technologies that can be applied to them. Here, we build on the renewed interest in using tree shrews ( Tupaia Belangeri ) in vision research and provide strong support for them as a model for studying visual perceptual decision-making. Tree shrews learned very quickly to perform a two-alternative forced choice contrast discrimination task, and they exhibited differences in response time distributions depending on the reward and punishment structure of the task. Specifically, they made occasional fast guesses when incorrect responses are punished by a constant increase in the interval between trials. This behavior was suppressed when faster incorrect responses were discouraged by longer inter-trial intervals. By fitting the behavioral data with two variants of racing diffusion decis...

Place code representation is ubiquitous in circuits that encode spatial parameters. For visually guided eye movements, neurons in many brain regions emit spikes when a stimulus is presented in their receptive fields and/or when a movement is directed into their movement fields. Crucially, individual neurons respond for a broad range of directions or eccentricities away from the optimal vector, making it difficult to decode the stimulus location or the saccade vector from each cell’s activity. We investigated whether it is possible to decode the spatial parameter with a population-level analysis, even when the optimal vectors are similar across neurons. Spiking activity and local field potentials (LFP) in the superior colliculus were recorded with a laminar probe as monkeys performed a delayed saccade task to one of eight targets radially equidistant in direction. A classifier was applied offline to decode the spatial configuration as the trial progresses from sensation to action. For spiking activity, deco...

Angular tuning is preferential sensory response to a directional stimulus and is observed in the whisker tactile system. In whisker hair follicles, there are at least three types of low threshold mechanoreceptors (LTMRs): rapidly adapting (RA), slowly adapting type 1 (SA1), and slowly adapting type 2 (SA2). These LTMRs display angular tuning but their properties remain incompletely studied. Here we used isolated rat whisker hair follicles and pressure-clamped single-fiber recordings to study angular tuning of these LTMRs. Angular tuning was determined with impulses elicited by ramp-and-hold deflection of whisker hair in 24 directions each at 15° for a total of 360°. We show that RA display impulses during ramp-up, both ramp-up and ramp-down, or ramp-down dynamic phases. Both SA1 and SA2 respond to angular stimuli with slowly adapting impulses in most angles. However, SA1 and SA2 show rapidly adapting responses in other angles. All the three types of LTMRs display strong angular tuning, and there is no sign...

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 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 individual visu...

Zebrafish retinal cone signals shift in spectral shape through larval, juvenile, and adult development as expression patterns of eight cone-opsin genes change. An algorithm extracting signal amplitudes for the component cone spectral types is developed and tested on two thyroxin receptor β2 (trβ2) gain-of-function lines crx:mYFP-2A-trβ2 and gnat2:mYFP-2A-trβ2 , allowing correlation between opsin signaling and opsin immunoreactivity in lines with different developmental timing and cell-type expression of this red-opsin-promoting transgene. Both adult transgenics became complete, or nearly complete, ‘red-cone dichromats’, with disproportionately large LWS1 opsin amplitudes as compared to controls, where LWS1 and LWS2 amplitudes were about equal, and significant signals from SWS1, SWS2, and Rh2 opsins were detected. But in transgenic larvae and juveniles of both lines it was LWS2 amplitudes that increased, with LWS1 cone signals rarely encountered. In gnat2:mYFP-2A-trβ2 embryos at 5 days post fertilization (d...

When looking around a visual scene, humans make saccadic eye movements to fixate objects of interest. While the extraocular muscles can execute saccades in any direction, not all saccade directions are equally likely: saccades in horizontal and vertical directions are most prevalent. Here, we asked if head orientation plays a role in determining saccade direction biases. Study participants (n = 14) viewed natural scenes and abstract fractals (radially symmetric patterns) through a virtual reality headset equipped with eye tracking. Participants’ heads were stabilized and tilted at -30°, 0°, or 30° while viewing the images, which could also be tilted by -30°, 0°, and 30° relative to the head. To determine if the biases in saccade direction changed with head tilt, we calculated polar histograms of saccade directions and cross-correlated pairs of histograms to find the angular displacement resulting in the maximum correlation. During free viewing of fractals, saccade biases largely followed the orientation of...

Hyperactivation of cyclin-dependent kinase 5 (CDK5) by p25, contributes to neuroinflammation causing neurodegeneration in Parkinson’s disease (PD) and Alzheimer's diseases (AD). 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 upon each single-point mutation. Interestingly, double-mutations also led to a severe decline in the activity of cPLA2 and 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 phosphorylatio...

A significant proportion of the human neurotypical population exhibits some degree of sensory eye dominance (SED), referring to the brain’s preferential processing of one eye’s input versus another. The neural substrates underlying this functional imbalance are not well known. Here, we investigated the relationship between visual white matter tract properties and SED in the human neurotypical population. Observers’ performance on two commonly used dichoptic tasks were used to index SED, along with performance on a third task to address a functional implication of binocular imbalance: stereovision. We show that diffusivity metrics of the optic radiations well predict behavioural SED metrics. We found no relationship between SED and stereosensitivity. Our data suggest that SED is not simply reflected by grey matter structural and functional alterations, as often suggested, but relates, at least in part to the microstructural properties of thalamocortical white matter. Significance Statement Sensory eye do...