Individual neurons in sensory cortices exhibit specific receptive fields based on their dendritic patterns. These dendritic morphologies are established and refined during the neonatal period through activity-dependent plasticity. This process can be visualized using two-photon in vivo time-lapse imaging, but sufficient spatiotemporal resolution is essential. We previously examined dendritic patterning from spiny stellate (SS) neurons, the major type of layer 4 (L4) neurons, in the mouse primary somatosensory cortex (barrel cortex), where mature dendrites display a strong orientation bias toward the barrel center. Longitudinal imaging at 8-h intervals revealed the long-term dynamics by which SS neurons acquire this unique dendritic pattern. However, the spatiotemporal resolution was insufficient to detect the more rapid changes in SS neuron dendrite morphology during the critical neonatal period. In the current study, we imaged neonatal L4 neurons hourly for 8 h and improved the spatial resolution by unifo...

Working memory can maintain sequential and concurrent information, and the load enhances the gamma-band oscillation during the delay period. To provide a unified account for these phenomena in working memory, we investigated a continuous network model consisting of pyramidal cells, high-threshold fast-spiking interneurons (FS), and low-threshold non-fast-spiking interneurons (nFS) for working memory of sequential and concurrent directional cues. Our model exhibits the gamma (30-100Hz) and beta (10-30Hz) band oscillation during the retention of both concurrent cues and sequential cues. We found that the beta oscillation results from the interaction between pyramidal cells and nFS, whereas the gamma oscillation emerges from the interaction between pyramidal cells and FS due to the strong excitation elicited by cue presentation, shedding light on the mechanism underlying the enhancement of gamma power in many cognitive executions. Significance Statement We constructed a spiking network to perform working m...

Human startle disease is associated with mutations in distinct genes encoding glycine receptors, transporters or interacting proteins at glycinergic synapses in spinal cord and brainstem. However, a significant number of diagnosed patients does not carry a mutation in the common genes GLRA1 , GLRB , and SLC6A5 . Recently, studies on SLC7A10 (Asc-1 alanine-serine-cysteine transporter) knockout mice displaying a startle disease-like phenotype hypothesized that this transporter might represent a novel candidate for human startle disease. Here, we screened 51 patients from our patient cohort negative for the common genes and found three exonic (one missense, two synonymous), seven intronic, and single nucleotide changes in the 5’ and 3’ untranslated regions. The identified missense mutation Asc-1G307R from a patient with startle disease and developmental delay was investigated in functional studies. At the molecular level, the mutation Asc-1G307R did not interfere with cell-surface expression, but disrupted gl...

The gradual accumulation of noisy evidence for or against options is the main step in the perceptual decision-making process. Using brain-wide electrophysiological recording in mice (Steinmetz et al., 2019), we examined neural correlates of evidence accumulation across brain areas. We demonstrated that the neurons with Drift-Diffusion-Model-like firing rate activity (i.e., evidence-sensitive ramping firing rate) were distributed across the brain. Exploring the underlying neural mechanism of evidence accumulation for the DDM-like neurons revealed different accumulation mechanisms (i.e. single and race) both within and across the brain areas. Our findings support the hypothesis that evidence accumulation is happening through multiple integration mechanisms in the brain. We further explored the timescale of the integration process in the single and race accumulator models. The results demonstrated that the accumulator microcircuits within each brain area had distinct properties in terms of their integration t...

It has been suggested that stochasticity acts in the formation of topographically ordered maps in the visual system through the opposing chemoaffinity and neural activity forces acting on the innervating nerve fibres being held in an unstable equilibrium. Evidence comes from the Islet2-EphA3 knockin mouse, in which approximately 50% of the retinal ganglion cells, distributed across the retina, acquire the EphA3 receptor, thus having an enhanced density of EphA which specifies retinotopic order along one axis of the retinocollicular map. Sampling EphA3 knockin maps in heterozygotes at different positions along the mediolateral extent of the colliculus had found single 1D maps (as in wild types), double maps (as in homozygous knockins) or both single and double maps. We constructed full 2D maps from the same mouse dataset. We found either single maps or maps where the visual field projects rostrally, with a part-projection more caudally to form a double map, the extent and location of this duplication varyin...

Respiratory sinus arrhythmia (RSA), the natural variation in heart rate synchronized with respiration, has been extensively studied in emotional and cognitive contexts. Various time or frequency-based methods using the cardiac signal have been proposed to analyze RSA. In this study, we present a novel approach that combines respiratory phase and heart rate to enable a more detailed analysis of RSA and its dynamics throughout the respiratory cycle. To facilitate the application of this method, we have implemented it in an open-source Python toolbox called physio. This toolbox includes essential functionalities for processing ECG and respiratory signals, while also introducing this new approach for RSA analysis. Inspired by previous research conducted by our group, this method enables a cycle-by-cycle analysis of RSA providing the possibility to correlate any respiratory feature to any RSA feature. By employing this approach, we aim to gain a more accurate understanding of the neural mechanisms associated wi...

It is often claimed that tools are embodied by their user, but whether the brain actually repurposes its body-based computations to perform similar tasks with tools is not known. A fundamental computation for localizing touch on the body is trilateration . Here, the location of touch on a limb is computed by integrating estimates of the distance between sensory input and its boundaries (e.g., elbow and wrist of the forearm). As evidence of this computational mechanism, tactile localization on a limb is most precise near its boundaries and lowest in the middle. Here we show that the brain repurposes trilateration to localize touch on a tool, despite large differences in initial sensory input compared to touch on the body. In a large sample of participants, we found that localizing touch on a tool produced the signature of trilateration, with highest precision close to the base and tip of the tool. A computational model of trilateration provided a good fit to the observed localization behavior. To further de...

The Drosophila mushroom body (MB) is an important model system for studying the synaptic mechanisms of associative learning. In this system, coincidence of odor-evoked calcium influx and dopaminergic input in the presynaptic terminals of Kenyon cells (KCs), the principal neurons of the MB, triggers long-term depression (LTD), which plays a critical role in olfactory learning. However, it is controversial whether such synaptic plasticity is accompanied by a corresponding decrease in odor-evoked calcium activity in the KC presynaptic terminals. Here, we address this question by inducing LTD by pairing odor presentation with optogenetic activation of dopaminergic neurons (DANs). This allows us to rigorously compare the changes at the pre- and postsynaptic sites in the same conditions. By imaging presynaptic acetylcholine release in the condition where LTD is reliably observed in the postsynaptic calcium signals, we show that neurotransmitter release from KCs is depressed selectively in the MB compartments inn...

Rhythms are a common feature of brain activity. Across different types of rhythms, the phase has been proposed to have functional consequences, thus requiring its accurate specification from noisy data. Phase is conventionally specified using techniques that presume a frequency band-limited rhythm. However, in practice, observed brain rhythms are typically non-sinusoidal and amplitude modulated. How these features impact methods to estimate phase remains unclear. To address this, we consider three phase estimation methods, each with different underlying assumptions about the rhythm. We apply these methods to rhythms simulated with different generative mechanisms and demonstrate inconsistency in phase estimates across the different methods. We propose two improvements to the practice of phase estimation: (1) estimating confidence in the phase estimate, and (2) examining the consistency of phase estimates between two (or more) methods. Significance Statement Rhythms in the brain can coordinate the activit...

The retinas of the vast majority of vertebrate species are termed “duplex” – that is, they contain both rod and cone photoreceptor neurons in different ratios. The retina of Little skate ( Leucoraja erinacea ) is a rarity among vertebrates because it contains only a single photoreceptor cell type and is thus “simplex”. This unique retina provides us with an important comparative model and an exciting opportunity to study retinal circuitry within the context of a visual system with a single photoreceptor cell type. What is perhaps even more intriguing is the fact that the Leucoraja retina is able use that single photoreceptor cell type to function under both scotopic and photopic ranges of illumination. Although some ultrastructural characteristics of skate photoreceptors have been examined previously, leading to a general description of them as “rods” largely based on outer segment morphology and rhodopsin expression, a detailed study of the fine anatomy of the entire cell and its synaptic connectivity is ...