Search bioRxiv⌕ Search

Biology subjects

Newman, E. L.

Publications and source records attributed to Newman, E. L..

At least 19 recordsLinked to original sources

Boundary Vector Cells Encode a Future-Biased Spectrum of Positions in the Rat

Spatial tuning is a hallmark property of neural firing in the hippocampal formation. Yet, that tuning is often less well correlated with the instantaneous current position of an animal than it is with an integrated version of the past or future state of the animal. Whether that encoding is biased towards past or future states and the extent to which it shows fixed versus multi-scale encoding varies across circuits and cell types. The temporal encoding properties of boundary vector cells of the subiculum are not well established. To address this here, we re-analyzed recordings of BVCs described previously by Lever et al. (2009) with multiple approaches. In the first, we asked if adding a temporal offset between the rat position and the spiking of a BVC increased the apparent spatial tuning in the firing rate map. We found that aligning BVC spiking with future states maximized the rate map spatial tuning. These results were mirrored in a second analysis that, instead of optimizing rate map spatial tuning, optimized how well the firing rate map predicted the BVC spiking. The second analysis also allowed us to ask whether that encoding is focused on a particular temporal horizon or whether the encoding captures behavior at multiple scales. To this end, for a given recording, we asked "How much time-integration of the behavioral state is the observed spiking most consistent with?" We observed a wide spectrum of time-constants of integration across cells, indicating that BVCs form a multiscale encoding of future states. The distribution of both offsets and integration rates observed across BVCs did not differ significantly from other, non-BVC, subiculum neurons. Taken together, these findings indicate that BVCs, along with other subiculum neurons, form a multi-scale encoding of future states.

neuroscience↗

Local adaptation of Gladiolus carneus to soil nutrient extremes in the Cape Floristic Region

PremiseWithin the hyper-diverse Cape Floristic Region (CFR), divergent edaphic niches are hypothesised as an important driver of lineage diversification. However, the evidence for local adaptation on contrasting soils in this region remains limited. Using a reciprocal translocation and common garden approach, we use the polymorphic geophyte Gladiolus carneus to test for local adaptation to soil properties along an elevational gradient. MethodsWe first quantified the edaphic niche of all ecotypes of G. carneus across its entire range and for three experimental populations used for reciprocal translocations. Next, under common garden conditions, we tested whether the three focal populations had a fitness advantage on their native soils relative to other populations. We then assessed whether those same populations showed evidence of local adaptation. Key resultsWe found that G. carneus ecotypes occupied distinct edaphic niches and that our three experimental populations occurred in nutrient-poor, intermediate-nutrient and nutrient-rich soil conditions. The common garden showed that seedlings native to the nutrient-rich and nutrient-poor sites, experienced a fitness advantage over non-native seedlings. Additionally, we found evidence of local adaptation at all translocation sites. Together, the common garden and reciprocal translocation suggests that edaphic conditions are contributing to local adaptation at the nutrient-rich and nutrient-poor sites. ConclusionsWe provide the first evidence of local adaptation to edaphic niches in the hyper-diverse Cape Floristic Region. These results suggest that edaphic conditions, along with other abiotic factors, may be important in driving incipient speciation in the CFR.

evolutionary biology↗

The role of secondary pollinators in the evolution of complex colour signals in a bimodal pollination system

Flower colour is recognized as a key trait influencing pollinator visitation and behaviour, evolved to match the sensory system of a particular pollinator group. However, some flowers combine colours associated with different pollinators, suggesting bimodal adaptation. The perennial herb Cyrtanthus obliquus produces red corollas with yellow tips and is pollinated by birds, but also by bees. To assess the role of the two pollinator categories in shaping selection on the bi-coloured corollas, we examined bee choices in arrays in which the colour signals of plants had been manipulated, and we quantified total as well as bird-mediated phenotypic selection on flower colour using both bird and bee visual models. Bees preferred flowers with a yellow signal over all-red flowers. The analysis of phenotypic selection indicated that both birds and bees influence net selection on flower colour, resulting in conflicting selection on the colour contrast between corolla and corolla tip. Our findings show that the optimal phenotype should depend on the relative importance of the two categories of pollinators in a given population, and are consistent with bimodal adaptation. This study fills an important gap by showing that secondary pollinators can contribute to selection on complex colour signals in angiosperm flowers.

evolutionary biology↗

Pollinator and flower morphology interact to influence pollen receipt

Pollinators are important drivers of floral divergence and speciation in plants. Here we investigate the effects of floral trait variation and trait matching on pollen receipt in two different plant species, Tritoniopsis revoluta (Iridaceae) and Nerine humilis (Amaryllidaceae) each visited by long-proboscid nemestrinid flies and solitary bees across their ranges. Using single visits by pollinators to flowers in populations with experimentally increased variance in floral morphology, we demonstrate that pollinators with different morphology affect pollen receipt differently through their interactions with floral traits. This study provides details of how the mechanical fit between floral and pollinator morphology may drive floral divergence through its effects on pollen deposition, both within populations using multiple pollinators and between populations with contrasting pollinators.

evolutionary biology↗

Repeated Binge-Like Alcohol Drinking Heightens Aggression in Mice

RationaleIn humans, alcohol drinking is a significant driver of violent behaviors such as assaults and homicides. While acute intoxication is known to produce heightened aggression, little is known about alcohols long-term effects. Emerging evidence, however, suggests that chronic alcohol intake can promote heightened aggression, including during abstinence and may also sensitize individuals to alcohols acute aggression-heightening effects. ObjectivesThe goal of this study was to test the effects of chronic binge-like ethanol drinking on both alcohol-involved and alcohol-uninvolved aggression in male CFW mice. We aimed to model individual differences in binge drinking and assess changes in aggression during both acute and protracted abstinence. ResultsAfter 5 weeks of Drinking in the Dark (DID), CFW mice that showed higher levels of EtOH drinking ( high drinkers, 1.33 g/kg/h) became more aggressive than low drinkers (0.45 g/kg/h) and H2O controls, as measured via frequency of attack bites during resident-intruder fighting. In the first aggressive encounter following 1 week of abstinence, animals with an alcohol drinking history initiate a fight more rapidly and with greater consistency than H2O controls. We also found that a single session of binge-like alcohol drinking acutely heightened aggression regardless of drinking history. ConclusionsThese results suggest that repeated binge-like alcohol drinking causes escalations in alcohol-uninvolved aggression during acute (in high drinkers) and protracted abstinence (in all alcohol drinkers). However, chronic alcohol intake does not appear to sensitize animals to alcohol-involved aggression. These findings support the utility of genetically heterogeneous CFW mice for modeling individual variability in alcohol-related aggression.

neuroscience↗

Ecological niche differentiation mediates near complete premating reproductive isolation within the Gladiolus carneus (Iridaceae) species complex.

Background and aimsEcological niche differentiation is well associated with intraspecific divergence of functional traits, which may lead to the evolution of premating reproductive isolation. However, the link between the ecological niches, trait divergence, and premating isolation remains poorly understood. This is particularly pertinent in hyper-diverse areas such as the Cape Floristic Region (CFR) of South Africa, where fine-scale ecological heterogeneity has been hypothesised as a major driver of speciation. Using the polymorphic geophyte Gladiolus carneus, endemic to the CFR, we test whether ecological niche differentiation mediates premating reproductive isolation. MethodsWe first tested whether newly and previously described Gladiolus carneus varieties were distinct based on their floral and vegetative morphology. Next, we documented each varietys abiotic niche, flowering phenology and pollination niche and further tested whether any resulting niche differentiation causes premating reproductive isolation. Key resultsSeven morphologically distinct varieties were identified, of which two of these are newly documented. Using niche modelling and multivariate analyses, we found that these varieties occupied distinct abiotic niches, resulting in strong ecogeographic isolation. They also had distinct flowering times, causing varying strengths of phenological isolation. For the pollinator niche, we found that all sampled populations had a single highly effective functional pollinator; however, at the variety level, there were no consistent trends leading to varying strengths in pollinator-mediated isolation. Across all varieties, ecogeographic isolation was the strongest gene flow barrier, which combined with phenological and pollinator-mediated isolation, causes near complete premating reproductive isolation. ConclusionsThese results suggest that ecological niche differentiation between Gladiolus carneus varieties may be contributing to incipient speciation within the species complex and further suggests that ecological niche differentiation may be a major driver of speciation in the hyper-diverse Cape Floristic Region.

evolutionary biology↗

Path integration impairments reveal early cognitive changes in Subjective Cognitive Decline

Path integration, the ability to track ones position using self-motion cues, is critically dependent on the grid cell network in the entorhinal cortex, a region vulnerable to early Alzheimers disease pathology. In this study, we examined path integration performance in individuals with subjective cognitive decline (SCD), a group at increased risk for Alzheimers disease, and healthy controls using an immersive virtual reality task. We developed a Bayesian computational model to decompose path integration errors into distinct components. SCD participants exhibited significantly higher path integration error, primarily driven by increased memory leak, while other modelling-derived error sources, such as velocity gain, sensory and reporting noise, remained comparable across groups. Our findings suggest that path integration deficits, specifically memory leak, may serve as an early marker of neurodegeneration in SCD and highlight the potential of self-motion-based navigation tasks for detecting pre-symptomatic Alzheimers disease-related cognitive changes. TeaserVirtual reality, modelling, and plasma biomarkers reveal path integration deficits in pre-symptomatic Alzheimers vs normal aging.

neuroscience↗

rTCT: Rodent Triangle Completion Task to facilitate translational study of path integration

Path integration is navigation in the absence of environmental landmarks and is a primary cognitive mechanism underlying spatial memory. Path integration performance is primarily assessed in humans using the Triangle Completion Task (TCT). In humans, TCT has shown promise for the early diagnosis of Alzheimers disease. In rodents, however, path integration is assessed using a wide variety of tasks but none of which currently provide a homologue for the TCT. As rodents are routinely used as preclinical models, homologous path integration tasks that result in comparable performance metrics between species are important. In the present study we developed and tested a novel rodent version of the triangle completion task to enhance cross species comparability of path integration performance. Rats were able to comprehend and perform the task. A group of Alzheimers disease model rats (TgF344-AD) exhibited similar path integration performance to their wild-type littermates; however, analysis of behavioural structure suggests use of differing behavioural strategies. This work establishes a novel rodent homologue of the triangle completion task, facilitating enhanced reverse translational study of human path integration.

neuroscience↗

Spermidine alleviates depression via control of the stress response

Depression is a stress-associated disorder, and it represents a major global health issue. Its pathophysiology is complex and remains insufficiently understood, with current medications often showing limited efficacy and undesirable side effects. Here, we identify imbalanced polyamine levels and dysregulated autophagy as key components of the acute stress response in humans, and as hallmarks of chronic stress and depressive disorders. Moreover, conventional antidepressant pharmacotherapy increases endogenous plasma concentrations of the polyamine spermidine exclusively in patients who respond to the treatment, suggesting a link between spermidine and successful outcomes. In a clinical trial, involving drug-naive depressed individuals, three weeks of spermidine supplementation increased autophagy and alleviated symptoms of depression. Behavioral and mechanistic findings of spermidine supplementation were validated in various mouse stress and depression models. In summary, spermidine supplementation mitigates polyamine dysregulation and stimulates autophagy under pathological stress conditions, offering a novel and well-tolerated treatment approach for stress-related depressive disorders.

neuroscience↗

Event boundaries drive norepinephrine release and distinctive neural representations of space in the rodent hippocampus

Episodic memories are temporally segmented around event boundaries that tend to coincide with moments of environmental change. During these times, the state of the brain should change rapidly, or reset, to ensure that the information encountered before and after an event boundary is encoded in different neuronal populations. Norepinephrine (NE) is thought to facilitate this network reorganization. However, it is unknown whether event boundaries drive NE release in the hippocampus and, if so, how NE release relates to changes in hippocampal firing patterns. The advent of the new GRABNE sensor now allows for the measurement of NE binding with sub-second resolution. Using this tool in mice, we tested whether NE is released into the dorsal hippocampus during event boundaries defined by unexpected transitions between spatial contexts and presentations of novel objections. We found that NE binding dynamics were well explained by the time elapsed after each of these environmental changes, and were not related to conditioned behaviors, exploratory bouts of movement, or reward. Familiarity with a spatial context accelerated the rate in which phasic NE binding decayed to baseline. Knowing when NE is elevated, we tested how hippocampal coding of space differs during these moments. Immediately after context transitions we observed relatively unique patterns of neural spiking which settled into a modal state at a similar rate in which NE returned to baseline. These results are consistent with a model wherein NE release drives hippocampal representations away from a steady-state attractor. We hypothesize that the distinctive neural codes observed after each event boundary may facilitate long-term memory and contribute to the neural basis for the primacy effect.

neuroscience↗

Cholinergic modulation of exploration in rats performing a spatial memory task

Spatial memory encoding depends in part on cholinergic modulation. How acetylcholine supports spatial memory encoding is not well understood. Prior studies indicate that acetylcholine release is correlated with exploration, including epochs of rearing onto hind legs. Here, to test whether elevated cholinergic tone increases the probability of rearing, we tracked rearing frequency and duration while optogenetically modulating the activity of choline acetyltransferase containing (i.e., acetylcholine producing) neurons of the medial septum in rats performing a spatial working memory task (n = 17 rats). The cholinergic neurons were optogenetically inhibited using halorhodopsin for the duration that rats occupied two of the four open arms during the study phase of an 8-arm radial arm maze win-shift task. Comparing rats behavior in the two arm types showed that rearing frequency was not changed but the average duration of rearing epochs became significantly longer. This effect on rearing was observed during optogenetic inhibition but not during sham inhibition or in rats that received infusions of a fluorescent reporter virus (i.e., without halorhodopsin; n = 6 rats). Optogenetic inhibition of cholinergic neurons during the pre-trial waiting phase had no significant effect on rearing, indicating a context-specificity of the observed effects. These results are significant in that they indicate that cholinergic neuron activity in the medial septum is correlated with rearing not because it motivates an exploratory state but because it contributes to the processing of information acquired while rearing.

neuroscience↗

Histone H3 serotonylation dynamics in dorsal raphe nucleus contribute to stress-induced gene expression and behavior

BackgroundMajor depressive disorder (MDD), along with related mood disorders, is a debilitating illness that affects millions of individuals worldwide. While chronic stress increases incidence levels of mood disorders, stress-mediated disruptions in brain function that precipitate these illnesses remain elusive. Serotonin-associated antidepressants (ADs) remain the first line of therapy for many with depressive symptoms, yet low remission rates and delays between treatment and symptomatic alleviation have prompted skepticism regarding precise roles for serotonin in the precipitation of mood disorders. Our group recently demonstrated that serotonin epigenetically modifies histone proteins (H3K4me3Q5ser) to regulate transcriptional permissiveness in brain. However, this phenomenon has not yet been explored following stress and/or AD exposures. MethodsWe employed a combination of genome-wide and biochemical analyses in dorsal raphe nucleus (DRN) of male and female mice exposed to chronic social defeat stress to examine the impact of stress exposures on H3K4me3Q5ser dynamics, as well as associations between the mark and stress-induced gene expression. We additionally assessed stress-induced regulation of H3K4me3Q5ser following AD exposures, and employed viral-mediated gene therapy to reduce H3K4me3Q5ser levels in DRN and examine the impact on stress-associated gene expression and behavior. ResultsWe found that H3K4me3Q5ser plays important roles in stress-mediated transcriptional plasticity. Chronically stressed mice displayed dysregulated H3K4me3Q5ser dynamics in DRN, with both AD- and viral-mediated disruption of these dynamics proving sufficient to rescue stress-mediated gene expression and behavior. ConclusionsThese findings establish a neurotransmission-independent role for serotonin in stress-/AD-associated transcriptional and behavioral plasticity in DRN.

neuroscience↗

Hippocampal inactivation during rearing on hind legs impairs spatial memory

Spatial memory requires an intact hippocampus. Hippocampal function during epochs of locomotion and quiet rest (e.g., grooming and reward consumption) have been the target of extensive study. However, during navigation rats frequently rear up on to their hind legs and the importance of hippocampal activity during these periods of attentive sampling for spatial memory is unknown. To address this, we tested the necessity of dorsal hippocampal activity during rearing epochs in the study phase of a delayed win-shift task for memory performance in the subsequent test phase. Hippocampal activity was manipulated with closed-loop, bilateral, optogenetic inactivation. Spatial memory accuracy was significantly and selectively reduced when the dorsal hippocampus was inactivated during rearing epochs at encoding. These data show that hippocampal activity during periods of rearing can be important for spatial memory, revealing a novel link between hippocampal function during epochs of rearing and spatial memory.

neuroscience↗

Structural anther mimics improve reproductive success through dishonest signalling that enhances both attraction and the morphological fit of pollinators with flowers

O_LINumerous studies have identified traits associated with pollen mimicry, however, the processes underlying floral deception remains poorly documented for these structures. We studied the importance of attraction and mechanical fit of anther mimics in Tritonia laxifolia (Iridaceae) and their relative contributions to reproductive success. C_LIO_LITo determine anther mimics role in pollinator attraction, we offered bees binary preferences to flowers painted with UV absorbent and reflecting paint. We also conducted preference experiments between flowers with excised anther mimics and unmanipulated controls, from which mechanical fit was assessed using single visits. Anther mimics effects on female reproductive success was determined using similar treatments, but on rooted plants. C_LIO_LIBees preferred UV absorbent over UV reflecting anther mimics. Preference for flowers with and without the three-dimensional structures was equal. Single visits resulted in more pollen deposition on unmanipulated controls over flowers with their anther mimics excised, which was directly linked to pollen-collecting behaviour. Controls with unmanipulated anther mimics experienced more seed set than those with their anther mimics excised. C_LIO_LIThis study provides insights into pollinator-mediated selection on deceptive floral signals and shows that three-dimensional anther mimics increases reproductive success through both attraction and pollen collecting behaviours that improves the fit between flowers and pollinators. C_LI

ecology↗

Genome-wide transcriptional profiling uncovers a similar oligodendrocyte-related transcriptional response to acute and chronic alcohol drinking in the amygdala

Alcohol intake progressively increases after prolonged consumption of alcohol, but relatively few new therapeutics targeting development of alcohol use disorder (AUD) have been validated. Here, we conducted a genome-wide RNA-sequencing (RNA-seq) analysis in mice exposed to different modes (acute vs chronic) of ethanol drinking. We focused on transcriptional profiles in the amygdala including the central and basolateral subnuclei, a brain area previously implicated in alcohol drinking and seeking, demonstrating distinct gene expression patterns and canonical pathways induced by both acute and chronic intake. Surprisingly, both drinking modes triggered similar transcriptional changes, including up-regulation of ribosome-related/translational pathways and myelination pathways, and down-regulation of chromatin binding and histone modification. Notably, multiple genes that were significantly regulated in mouse amygdala with alcohol drinking, including Atp2b1, Slc4a7, Nfkb1, Nts, and Hdac2, among others had previously been associated with human AUD via GWAS or other genomic studies. In addition, analyses of hub genes and upstream regulatory pathways predicted that voluntary ethanol consumption affects epigenetic changes via histone deacetylation pathways, oligodendrocyte and myelin function, and oligodendrocyte-related transcriptional factor, Sox17. Overall, our results suggest that the transcriptional landscape in the central and basolateral subnuclei of the amygdala is sensitive to voluntary alcohol drinking. They provide a unique resource of gene expression data for future translational studies examining transcriptional mechanisms underlying the development of AUD due to alcohol consumption.

neuroscience↗

Inhibition-Dominated Rich-Club Shapes Dynamics in Cortical Microcircuits of Awake Behaving Mice

Functional networks of cortical neurons contain highly interconnected hubs, forming a rich-club structure. However, the cell type composition within this distinct subnetwork and how it influences large-scale network dynamics is unclear. Using spontaneous activity recorded from hundreds of cortical neurons in orbitofrontal cortex of awake behaving mice and from organotypic cultures, we show that the rich-club is disproportionately composed of inhibitory neurons, and that inhibitory neurons within the rich-club are significantly more synchronous than other neurons. At the population level, neurons in the rich-club exert higher than expected Granger causal influence on overall population activity at a broad range of frequencies compared to other neurons. Finally, neuronal avalanche duration is significantly correlated with the fraction of rich neurons that participate in the avalanche. Together, these results suggest an unexpected role of a highly connected, inhibition-rich subnetwork in driving and sustaining activity in local cortical networks. SIGNIFICANCE STATEMENTIt is widely believed that the relative abundance of excitatory and inhibitory neurons in cortical circuits is roughly 4:1. This relative abundance has been widely used to construct numerous cortical network models. Here we show that contrary to this notion, a sub-network of highly connected hub neurons (rich-club) consists of a higher abundance of inhibitory neurons compared to that found in the entire network or the non-rich subnetwork. Inhibitory hub neurons contribute to higher synchrony within the rich club compared to the rest of the network. Strikingly, higher activation of the inhibition-dominated rich club strongly correlates with longer avalanches in cortical circuits. Our findings reveal how network topology combined with cell-type specificity orchestrates population wide activity in cortical microcircuits.

neuroscience↗

Synergistic neural computation is greater downstream of recurrent connectivity in organotypic cortical cultures

The directionality of network information flow dictates how networks process information. A central component of information processing in both biological and artificial neural networks is their ability to perform synergistic integration-a type of computation. We established previously that synergistic integration varies directly with the strength of feedforward information flow. However, the relationships between both recurrent and feedback information flow and synergistic integration remain unknown. To address this, we analyzed the spiking activity of hundreds of neurons in organotypic cultures of mouse cortex. We asked how empirically observed synergistic integration varied with local functional network structure that was categorized into motifs with varying recurrent and feedback information flow. We found that synergistic integration was elevated in motifs with greater recurrent information flow beyond that expected from the local feedforward information flow. Feedback information flow was interrelated with feedforward information flow and was associated with decreased synergistic integration. Our results indicate that synergistic integration is distinctly influenced by the directionality of local information flow. Author SummaryNetworks compute information. That is, they modify inputs to generate distinct outputs. These computations are an important component of network information processing. Knowing how the routing of information in a network influences computation is therefore crucial. Here we asked how a key form of computation--synergistic integration--is related to the direction of local information flow in networks of spiking cortical neurons. Specifically, we asked how information flow between input neurons (i.e., recurrent information flow) and information flow from output neurons to input neurons (i.e., feedback information flow) was related to the amount of synergistic integration performed by output neurons. We found that greater synergistic integration occurred where there was more recurrent information flow. And, lesser synergistic integration occurred where there was more feedback information flow relative to feedforward information flow. These results show that computation, in the form of synergistic integration, is distinctly influenced by the directionality of local information flow. Such work is valuable for predicting where and how network computation occurs and for designing networks with desired computational abilities.

neuroscience↗

Correlated activity favors synergistic processing in local cortical networks at synaptically-relevant timescales

Neural information processing is widely understood to depend on correlations in neuronal activity. However, whether correlation is favorable or not is contentious. Here, we sought to determine how correlated activity and information processing are related in cortical circuits. Using recordings of hundreds of spiking neurons in organotypic cultures of mouse neocortex, we asked whether mutual information between neurons that feed into a common third neuron increased synergistic information processing by the receiving neuron. We found that mutual information and synergistic processing were positively related at synaptic timescales (0.05-14 ms), where mutual information values were low. This effect was mediated by the increase in information transmission--of which synergistic processing is a component--that resulted as mutual information grew. However, at extrasynaptic windows (up to 3000 ms), where mutual information values were high, the relationship between mutual information and synergistic processing became negative. In this regime, greater mutual information resulted in a disproportionate increase in redundancy relative to information transmission. These results indicate that the emergence of synergistic processing from correlated activity differs according to timescale and correlation regime. In a low-correlation regime, synergistic processing increases with greater correlation, and in a high correlation regime, synergistic processing decreases with greater correlation. AUTHOR SUMMARYIn the present work, we address the question of whether correlated activity in functional networks of cortical circuits supports neural computation. To do so, we combined network analysis with information theoretic tools to analyze the spiking activity of hundreds of neurons recorded from organotypic cultures of mouse somatosensory cortex. We found that, at timescales most relevant to direct neuronal communication, neurons with more correlated activity predicted greater computation, suggesting that correlated activity does support computation in cortical circuits. Importantly, this result reversed at timescales less relevant to direct neuronal communication, where even greater correlated activity predicted decreased computation. Thus, the relationship between correlated activity and computation depends on the timescale and the degree of correlation in neuronal interactions.

neuroscience↗