Biology subjects

Love, T.

Publications and source records attributed to Love, T..

7 recordsLinked to original sources

bioRxiv2024

Amygdalo-nigral inputs target dopaminergic and GABAergic neurons in the primate: a view from dendrites and soma

The central nucleus (CeN) of the amygdala is an important afferent to the DA system that mediates motivated learning. We previously found that CeN terminals in nonhuman primates primarily overlap the elongated lateral VTA (parabrachial pigmented nucleus, PBP, A10), and retrorubral field(A8) subregion. Here, we examined CeN afferent contacts on cell somata and proximal dendrites of DA and GABA neurons, and distal dendrites of each, using confocal and electron microscopy (EM) methods, respectively. At the soma/proximal dendrites, the proportion of TH+ and GAD1+ cells receiving at least one CeN afferent contact was surprisingly similar (TH = 0.55: GAD1=0.55 in PBP; TH = 0.56; GAD1 =0.51 in A8), with the vast majority of contacted TH+ and GAD1+ soma/proximal dendrites received 1-2 contacts. Similar numbers of tracer-labeled terminals also contacted TH-positive and GAD1-positive small dendrites and/or spines (39% of all contacted dendrites were either TH- or GAD1-labeled). Overall, axon terminals had more symmetric (putative inhibitory) axonal contacts with no difference in the relative distribution in the PBP versus A8, or onto TH+ versus GAD1+ dendrites/spines in either region. The striking uniformity in the amygdalonigral projection across the PBP-A8 terminal field suggests that neither neurotransmitter phenotype nor midbrain location dictates likelihood of a terminal contact. We discuss how this afferent uniformity can play out in recently discovered differences in DA:GABA cell densities between the PBP and A8, and affect specific outputs. Significance statementThe amygdalas central nucleus (CeN) channels salient cues to influence both appetitive and aversive responses via DA outputs. In higher species, the broad CeN terminal field overlaps the parabrachial pigmented nucleus ( lateral A10) and the retrorubral field (A8). We quantified terminal contacts in each region on DA and GABAergic soma/proximal dendrites and small distal dendrites. There was striking uniformity in contacts on DA and GABAergic cells, regardless of soma and dendritic compartment, in both regions. Most contacts were symmetric (putative inhibitory) with little change in the ratio of inhibitory to excitatory contacts by region. We conclude that post-synaptic shifts in DA-GABA ratios are key to understanding how these relatively uniform inputs can produce diverse effects on outputs.

neuroscience↗

bioRxiv2023

Immature neurons in the primate amygdala: changes with early development and disrupted early environment

In human and nonhuman primates, the amygdala paralaminar nucleus (PL) contains immature neurons. To explore the PLs potential for cellular growth during development, we compared PL cells in 1) infant and adolescent macaques (control, maternally-reared), and in 2) infant macaques that experienced separation from their mother in the first month of life. In maternally-reared animals, the adolescent PL had fewer immature neurons, more mature neurons, and larger immature soma volumes compared to infant PL. There were also fewer total neurons (immature plus mature) in adolescent versus infant PL, suggesting that some neurons move out of the PL by adolescence. Maternal separation did not change mean immature or mature neuron counts in infant PL. However, across all infant animals, immature neuron soma volume was strongly correlated with mature neuron counts. tbr-1 mRNA, a transcript required for glutamatergic neuron maturation, is significantly reduced in the maternally-separated infant PL (DeCampo et al, 2017), and was also positively correlated with mature neuron counts in infant PL. We conclude that immature neurons gradually mature by adolescence, and that the stress of maternal separation may shift this trajectory, as revealed by correlations between tbr1mRNA and mature neuron numbers across animals.

neuroscience↗

bioRxiv2023

A Model-Based Hierarchical Bayesian Approach to Sholl Analysis

SO_SCPLOWUMMARYC_SCPLOWDue to the link between microglial morphology and function, morphological changes in microglia are frequently used to identify pathological immune responses in the central nervous system. In the absence of pathology, microglia are responsible for maintaining homeostasis, and their morphology can be indicative of how the healthy brain behaves in the presence of external stimuli and genetic differences. Despite recent interest in high throughput methods for morphological analysis, Sholl analysis is still the gold standard for quantifying microglia morphology via imaging data. Often, the raw data are naturally hierarchical, minimally including many cells per image and many images per animal. However, existing methods for performing downstream inference on Sholl data rely on truncating this hierarchy so rudimentary statistical testing procedures can be used. To fill this longstanding gap, we introduce a fully parametric model-based approach for analyzing Sholl data. We generalize our model to a hierarchical Bayesian framework so that inference can be performed without aggressive reduction of otherwise very rich data. We apply our model to three real data examples and perform simulation studies comparing the proposed method with a popular alternative.

neuroscience↗

bioRxiv2022

Structural equation models suggest that on-farm non-crop vegetation removal is not associated with improved food safety outcomes but is linked to impaired water quality

While growers have reported pressures to minimize wildlife intrusion into produce fields through non-crop vegetation (NCV) removal, NCV provides key ecosystem services. To model food safety and environmental tradeoffs associated with NCV removal, published and publicly available food safety and water quality data from the Northeastern USA were obtained. Because data on NCV removal are not widely available, forest-wetland cover was used as a proxy, consistent with previous studies. Structural equation models (SEMs) were used to quantify the effect of forest-wetland cover on (i) food safety outcomes (e.g., detecting pathogens in soil) and (ii) water quality (e.g., nutrient levels). Based on the SEMs, NCV was not associated with or had a protective effect on food safety outcomes (more NCV was associated with a reduced likelihood of pathogen detection). The probabilities of detecting Listeria spp. in soil (Effect Estimate [EE]=-0.17; P=0.005) and enterohemorrhagic Escherichia coli in stream samples (EE=-0.27; P<0.001) were negatively associated with the amount of NCV surrounding the sampling site. Higher amounts of NCV were also associated with lower nutrient, salinity, and sediment levels and higher dissolved oxygen levels. Total phosphorous levels were negatively associated with the amount of NCV in the upstream watershed (EE=-0.27; P<0.001). Similar negative associations (P<0.05) were observed for other physicochemical parameters, such as nitrate (EE=-0.38). Our findings suggest that NCV should not be considered an inherent produce safety risk or result in farm audit demerits. This study also provides a framework for evaluating environmental trade-offs associated with using specific preharvest food safety strategies. ImportanceCurrently, on-farm food safety decisions are typically made independently of conservation considerations, often with detrimental impacts on agroecosystems. Co-managing agricultural environments to simultaneously meet conservation and food safety aims is complicated because farms are closely linked to surrounding environments, and management decisions can have unexpected environmental, economic, and food safety consequences. Thus, there is a need for research on the conservation and food safety trade-offs associated with implementing specific preharvest food safety practices. Understanding these trade-offs is critical for developing adaptive co-management strategies and ensuring the short and long-term safety, sustainability, and profitability of agricultural systems. This study quantifies tradeoffs and synergies between food safety and environmental aims, and outlines a framework for modeling trade-offs and synergies between management aims that can be used to support future co-management research.

ecology↗

bioRxiv2020

The Neuroanatomy of Speech Processing: A Large-Scale Lesion Study

The neural basis of language has been studied for centuries, yet the networks critically involved in simply identifying or understanding a spoken word remain elusive. Several functional-anatomical models of critical neural substrates of receptive speech have been proposed, including (1) auditory-related regions in the left mid-posterior superior temporal lobe, (2) motor-related regions in the left frontal lobe (in normal and/or noisy conditions), the left anterior superior temporal lobe, or (4) bilateral mid-posterior superior temporal areas. One difficulty in comparing these models is that they often focus on different aspects of the sound-to-meaning pathway and are supported by different types of stimuli and tasks. Two auditory tasks that are typically used in separate studies--syllable discrimination and word comprehension--often yield different conclusions. We assessed syllable discrimination (words and nonwords) and word comprehension (clear speech and with a noise masker) in 158 individuals with focal brain damage: left (n=113) or right (n=19) hemisphere stroke, left (n=18) or right (n=8) anterior temporal lobectomy, and 26 neurologically-intact controls. Discrimination and comprehension tasks are doubly dissociable both behaviorally and neurologically. In support of a bilateral model, clear speech comprehension was near ceiling in 95% of left stroke cases and right temporal damage impaired syllable discrimination. Lesion-symptom mapping analyses for the syllable discrimination and noisy word comprehension tasks each implicated most of the left superior temporal gyrus (STG). Comprehension but not discrimination tasks also implicated the left pMTG, while discrimination but not comprehension tasks also implicated more dorsal sensorimotor regions in posterior perisylvian cortex.

neuroscience↗

bioRxiv2017

Statistical Approaches to Decreasing the Discrepancy of Non-detects in qPCR Data

Quantitative real-time PCR (qPCR) is one of the most widely used methods to measure gene expression. Despite extensive research in qPCR laboratory protocols, normalization, and statistical analysis, little attention has been given to qPCR non-detects - those reactions failing to produce a minimum amount of signal. While most current software replaces these non-detects with a value representing the limit of detection, recent work suggests that this introduces substantial bias in estimation of both absolute and differential expression. Recently developed single imputation procedures, while better than previously used methods, underestimate residual variance, which can lead to anti-conservative inference. We propose to treat non-detects as non-random missing data, model the missing data mechanism, and use this model to impute missing values or obtain direct estimates of relevant model parameters. To account for the uncertainty inherent in the imputation, we propose a multiple imputation procedure, which provides a set of plausible values for each non-detect. In the proposed modeling framework, there are three sources of uncertainty: parameter estimation, the missing data mechanism, and measurement error. All three sources of variability are incorporated in the multiple imputation and direct estimation algorithms. We demonstrate the applicability of these methods on three real qPCR data sets and perform an extensive simulation study to assess model sensitivity to misspecification of the missing data mechanism, to the number of replicates within the sample, and to the overall size of the data set. The proposed methods result in unbiased estimates of the model parameters; therefore, these approaches may be beneficial when estimating both absolute and differential gene expression. The developed methods are implemented in the R/Bioconductor package nondetects. The statistical methods introduced here reduce discrepancies in gene expression values derived from qPCR experiments, providing more confidence in generating scientific hypotheses and performing downstream analysis.

bioinformatics↗

bioRxiv2017

The neurobiology of agrammatic sentence comprehension: a lesion study

Brocas area has long been implicated in sentence comprehension. Damage to this region is thought to be the central source of \"agrammatic comprehension\" in which performance is substantially worse (and near chance) on sentences with noncanonical word orders compared to canonical word order sentences (in English). This claim is supported by functional neuroimaging studies demonstrating greater activation in Brocas area for noncanonical versus canonical sentences. However, functional neuroimaging studies also have frequently implicated the anterior temporal lobe (ATL) in sentence processing more broadly, and recent lesion-symptom mapping studies have implicated the ATL and mid temporal regions in agrammatic comprehension. The present study investigates these seemingly conflicting findings in 66 left hemisphere patients with chronic focal cerebral damage. Patients completed two sentence comprehension measures, sentence-picture matching and plausibility judgments. Patients with damage including Brocas area (but excluding the temporal lobe; n=11) on average did not exhibit the expected agrammatic comprehension pattern, e.g. their performance was > 80% on noncanonical sentences in the sentence-picture matching task. Patients with ATL damage (n=18) also did not exhibit an agrammatic comprehension pattern. Across our entire patient sample, the lesions of patients with agrammatic comprehension patterns in either task had maximal overlap in posterior superior temporal and inferior parietal regions. Using voxel-based lesion symptom mapping (VLSM), we find that lower performances on canonical and noncanonical sentences in each task are both associated with damage to a large left superior temporal-inferior parietal network including portions of the ATL, but not Brocas area. Notably however, response bias in plausibility judgments was significantly associated with damage to inferior frontal cortex, including gray and white matter in Brocas area, suggesting that the contribution of Brocas area to sentence comprehension may be related to task-related cognitive demands.

neuroscience↗