Biology subjects

Jacob, A. L.

Publications and source records attributed to Jacob, A. L..

6 recordsLinked to original sources

bioRxiv2025

Lack of ADAP1/Centaurin-α1 Ameliorates Cognitive Impairment and Neuropathological Hallmarks in a Mouse Model of Alzheimer's Disease

ArfGAP, with dual PH domain-containing protein 1/Centaurin-1 (ADAP1CentA1), is a brain-enriched and highly conserved Arf6 GTPase-activating and Ras-anchoring protein. ADAP1 is involved in dendritic outgrowth and arborization, synaptogenesis, and axonal polarization by regulating the dynamics of the actin cytoskeleton. An increased level of ADAP1 and its association with amyloid plaques in the human Alzheimers disease (AD) brain suggest a role for this protein in AD progression. To understand the role of ADAP1/CentA1 in neurodegeneration, we crossbred CentA1 KO mice with the hAPP-J20 mouse model of AD (J20 x CentA1 KO). We then evaluated the gene expression profile and the behavioral and neuropathological hallmarks of AD to determine the impact of eliminating ADAP1/CentA1 expression on AD-related phenotypes. Spatial memory assessed by the Morris Water Maze test showed significant impairment in J20 mice, which was rescued by the deletion of CentA1. Neuropathological hallmarks of AD, such as deposits of amyloid plaques and neuroinflammation, were significantly reduced in the AD model mice with CentA1 KO background. To identify potential mediators of AD phenotype rescue, we analyzed differentially expressed genes (DEGs) between genotypes, by employing transcriptome profiling with Nanostring nCounter Neuropathology and Neuroinflammation panels. We found significant upregulation of genes associated with apoptosis and gliosis in the brain of J20 mice. However, many of these genes, including the pro-apoptotic gene, Bid, were restored in the brains of J20 x CentA1 KO mice compared to J20 mice. In summary, our data indicate that CentA1 is required for the progression of AD phenotypes and that targeting CentA1 signaling at mitochondria might have therapeutic potential for AD prevention or treatment. SIGNIFICANCE STATEMENTADAP1/Centaurin-1 (CentA1) is highly enriched in the brain and increased CentA1 level has been linked to Alzheimers disease (AD). However, the precise role of ADAP1 in the pathogenesis of AD is poorly understood. We found that genetic deletion of CentA1 in the AD model mice rescues the pathological hallmarks of AD, including loss of dendritic spines in the hippocampus, amyloid plaque deposition, neuroinflammation and spatial memory deficits. Transcriptome analysis of forebrain samples using NanoString nCounter panels for 880 genes, identified the pro-apoptotic protein, Bid, with significantly reduced expression in the J20 mice on ADAP1 KO background. These findings point towards a role of ADAP1 in the activation of the mitochondrial pathways of death associated with the progression of neurodegeneration.

neuroscience↗

bioRxiv2024

Flexible EMG arrays with integrated electronics for scalable electrode density

Recent developments in electrode technology have demonstrated the power of flexible microelectrode arrays (FMEAs) for measuring muscle activity at high resolution. We recently introduced the Myomatrix array, an FMEA optimized for measuring the activity of individual motor units (the collection of muscle fibers innervated by a single motor neuron) [1] in freely behaving animals. Although FMEAs are fundamentally changing the way electromyography (EMG) is acquired, the number of recording channels is limited by the size of the plug that interfaces with the signal processing hardware and the density of electrode connections on the array. Increasing EMG channel count and supporting electrophysiological studies in smaller animals depends on two seemingly incompatible goals: reducing device size while increasing the number of recording channels. The solution to these goals is to increase the channel count per wire output. Current off-the-shelf designs require a separate headstage and FMEA to be used simultaneously. In our prior devices [1], each FMEA had a dedicated wire output for every electrode input, creating a channel density of 1:1. To improve this channel density, we have developed an FMEA with an integrated digital amplifier (Bare-Die RHD2216, INTAN INC, USA). The design of the FMEA reduces the footprint of the devices back end by 74% and relocates the Intan bare die from the headstage to the FMEA itself, creating a channel density of 1:3.2. Our methodology combines standard FMEA microfabrication with wire-bonding and surface-mounted components, enabling direct integration into a Serial Peripheral Interface (SPI) connection into the device itself, without any separate headstage. With this initial device there is a 1 : 3.2 channel density; however, our method allows using other bare die amplifiers (Intan, Inc., USA) for a channel density of 1:12.8. Our findings present a robust technique for chip embedding in custom FMEAs applicable to in-vivo electrophysiology

neuroscience↗

bioRxiv2024

Advancements in monitoring: a comparison of traditional and application-based tools for measuring outdoor recreation

Outdoor recreation has experienced a boom in recent years. While outdoor recreation provides wide-ranging benefits to human well-being and is an important feature of many protected and non-protected areas, there are growing concerns about the sustainability of recreation with the increased pressures placed on ecological systems and visitor experiences. These concerns emphasize the need for managers to access accurate and timely recreation data at scales that match the growing recreation footprint. Here, we compare spatial and temporal patterns of winter and summer recreation use using traditional and application-based tools across the Columbia and Canadian Rocky Mountains of western Canada. We demonstrate how recreation use can be estimated using traditional and application-based tools, although their accuracy and utility varies across space, season and activity type. Cameras and counters captured similar broad-scale patterns in count estimates of pedestrians and all recreation activities. Application-based data provided detailed spatiotemporal information on recreation use, but datasets were biased towards specific recreation types and did not represent the full recreation population. For instance, Strava Metro data was more suited for capturing broad-scale spatial patterns in biking than pedestrian recreation. Traditional tools including aerial surveys and participatory mapping captured coarser information on the intensity and extent of recreation, with the former tool capturing areas with low recreation intensity and the latter tool suited for capturing recreation information across large spatial and temporal scales. Application-based data should be supplemented with data from traditional tools including cameras or trail counters to identify biases in data and fill in data gaps. We provide a comparison of each tool for measuring recreation use, highlight each tools strengths and limitations, and suggest how to use these tools to address real-world monitoring and management scenarios. Our research contributes towards a better understanding of what tools are available to measure recreation and can help direct managers in selecting which tool, or combinations of tools, to use that can expand the rigor and scope of recreation research. This information can support decision-making and lead to the protection of ecological systems while allowing for high-quality recreation experiences. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=159 HEIGHT=200 SRC="FIGDIR/small/579662v1_ufig1.gif" ALT="Figure 1"> View larger version (76K): org.highwire.dtl.DTLVardef@95b5a7org.highwire.dtl.DTLVardef@c926d7org.highwire.dtl.DTLVardef@151296org.highwire.dtl.DTLVardef@1773d13_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2022

High-performance Flexible Microelectrode Array with PEDOT:PSS Coated 3D Micro-cones for Electromyographic Recording

High signal-to-noise ratio (SNR) electromyography (EMG) recordings are essential for identifying and analyzing single motor unit activity. While high-density electrodes allow for greater spatial resolution, the smaller electrode area translates to a higher impedance and lower SNR. In this study, we developed an implantable and flexible 3D microelectrode array (MEA) with low impedance that enables high-quality EMG recording. With polyimide micro-cones realized by standard photolithography process and PEDOT:PSS coating, this design can increase effective surface area by up to 250% and significantly improve electrical performance for electrode sites with various geometric surface areas, where the electrode impedance is at most improved by 99.3%. Acute EMG activity from mice was recorded by implanting the electrodes in vivo, and we were able to detect multiple individual motor units simultaneously and with high resolution (SNR >> 100). The charge storage capacity was measured to be 34.2 mC/cm2, indicating suitability of the electrodes for stimulation applications as well.

bioengineering↗

bioRxiv2021

Shared mechanisms of auditory and non-auditory vocal learning in the songbird brain

Songbirds and humans share the ability to adaptively modify their vocalizations based on sensory feedback. Prior studies have focused primarily on the role that auditory feedback plays in shaping vocal output throughout life. In contrast, it is unclear whether and how non-auditory information drives vocal plasticity. Here, we first used a reinforcement learning paradigm to establish that non-auditory feedback can drive vocal learning in adult songbirds. We then assessed the role of a songbird basal ganglia-thalamocortical pathway critical to auditory vocal learning in this novel form of vocal plasticity. We found that both this circuit and its dopaminergic inputs are necessary for non-auditory vocal learning, demonstrating that this pathway is not specialized exclusively for auditory-driven vocal learning. The ability of this circuit to use both auditory and non-auditory information to guide vocal learning may reflect a general principle for the neural systems that support vocal plasticity across species.

neuroscience↗

bioRxiv2019

Dopamine depletion affects vocal acoustics and disrupts sensorimotor adaptation in songbirds

Dopamine is hypothesized to convey important error information in reinforcement learning tasks with explicit appetitive or aversive cues. However, during motor skill learning the only available feedback signal is typically an animals evaluation of the sensory feedback arising from its own behavior, rather than any external reward or punishment. It has previously been shown that intact dopaminergic signaling from the ventral tegmental area - substantia nigra compacta complex (VTA/SNc) is necessary for vocal learning in response to an external aversive auditory cue in songbirds. However, the role of dopamine in learning in the absence of explicit external cues is still unclear. Here we used male Bengalese finches (Lonchura striata var. domestica) to test the hypothesis that dopamine signaling is necessary for self-evaluation driven sensorimotor learning. We combined 6-hydroxydopamine (6-OHDA) lesions of dopaminergic terminals within Area X, a songbird basal ganglia nucleus critical for vocal learning, with a headphones learning paradigm that shifted the birds auditory feedback and compared their learning to birds without lesions. We found that 6-OHDA lesions affected song behavior in two ways. First, over a period of days lesioned birds systemically lowered their pitch regardless of the presence or absence of auditory errors. Second, 6-OHDA lesioned birds also displayed severe deficits in sensorimotor learning as measured by their adaptive change in pitch in response to the pitch-shifted auditory error. Our results suggest roles for dopamine both in motor production and in auditory error processing during vocal learning.\n\nSignificance StatementDopamine has been hypothesized to convey a reward prediction error signal in learning tasks involving external reinforcement. However the role dopamine plays in tasks involving self-guided error correction in the absence of external reinforcement is much less clear. To address this question, we studied the role of dopamine in sensorimotor adaptation using male Bengalese finches, which spontaneously produce a complex motor behavior (song) and are capable of modulating their behavioral output in response to induced auditory errors. Our results reveal that in addition to conveying errors in motor performance, dopamine may also have a role in modulating effort and in choosing a corrective response to the auditory error.

neuroscience↗