Biology subjects

Jordan, R.

Publications and source records attributed to Jordan, R..

14 recordsLinked to original sources

bioRxiv2026

Spiking and neuromodulation during active experience shape visuomotor integration in V1 layer 2/3 neurons

Computational models propose that prediction errors drive plasticity to improve cancellation between sensory and predictive inputs - a process known as prediction error minimization. In mouse V1, layer 2/3 neurons exhibit spiking responses consistent with prediction errors between visual flow and locomotion-based predictions, but evidence that such spiking drives plasticity consistent with prediction error minimization is limited. To address this, we performed in vivo whole cell recordings in mice running in virtual reality while manipulating spike rates via closed-loop locomotion-coupled current injection. Spiking during visuomotor experience altered locomotion-related inputs in a firing rate-dependent manner. The direction of change depended on each neurons visual responsiveness, increasing the opposition between locomotion-related and visual inputs. Analyzing a published two-photon calcium imaging dataset, we demonstrate that a similar activity-dependent reorganization of visuomotor inputs is evident at the population level, but only when locus coeruleus axons were optogenetically activated during visuomotor experience. Together, our results provide evidence for refinements of prediction error computation in layer 2/3 that are driven by spiking and facilitated by neuromodulation across active experience.

neuroscience↗

bioRxiv2026

Australian giant kelp genome assemblies show distinct Southern Hemisphere genetics

Giant kelp, Macrocystis pyrifera, occurs across northern and southern Hemisphere temperate coasts and is at high risk from ocean warming. Few giant kelp forests remain across the Southeast Australian shelf, while a handful of forests are actively being restored. Genomic resources can greatly aid in the conservation of remnant populations and enhance restoration efforts. Reference genomes are a fundamental resource as they are a prerequisite to, or enhance, many analyses used in conservation genomics. A single reference genome is available for giant kelp, assembled from a Californian haploid specimen. However, increasing evidence of genetic divergence between Northern and Southern Hemisphere populations highlights the need for regionally representative reference genomes. Here, we present two genome assemblies from the diploid vegetative tissue of Australian giant kelp specimens. We performed de novo genome assembly using long-read sequencing (PacBio HiFi and ONT R10.4 Simplex) and scaffolded the assemblies with the ONT reads, assembling 98-99% of the genomes into 35 pseudo-chromosomes. Genome sizes ranged from 528-534 Mbp, with BUSCO completeness scores of 97-98% and QV scores of 51-52. Genome annotation identified 17,565-17,800 genes in the Australian genomes. Genomic divergence between the Australian and Californian giant kelp genomes was seven-fold greater than between Australian genomes (1.5% vs 0.2%), supporting a Northern-Southern Hemisphere genetic divergence. Functional divergence was also observed between Australian and Californian genomes, reflected by differing patterns of enrichment in gene ontologies linked to energy metabolism, proteostasis and stress responses. These two new genome assemblies will serve as valuable resources for ongoing research into Southern Hemisphere giant kelp genetics, while providing the basis for genomic-guided conservation and restoration of remnant giant kelp forests in Australia.

genomics↗

bioRxiv2024

Quantification of the effect of hemodynamic occlusion in two-photon imaging

The last few years have seen an explosion in the number of tools available to measure neuronal activity using fluorescence imaging (Chen et al., 2013; Feng et al., 2019; Jing et al., 2019; Sun et al., 2018; Wan et al., 2021). When performed in vivo, these measurements are invariably contaminated by hemodynamic occlusion artifacts. In widefield calcium imaging, this problem is well recognized. For two-photon imaging, however, the effects of hemodynamic occlusion have only been sparsely characterized. Here we perform a quantification of hemodynamic occlusion effects using measurements of fluorescence changes observed with GFP expression using both widefield and two-photon imaging. We find that in many instances the magnitude of signal changes attributable to hemodynamic occlusion is comparable to that observed with activity sensors. Moreover, we find that hemodynamic occlusion effects were spatially heterogeneous, both over cortical regions and across cortical depth, and exhibited a complex relationship with behavior. Thus, hemodynamic occlusion is an important caveat to consider when analyzing and interpreting not just widefield but also two-photon imaging data.

neuroscience↗

bioRxiv2024

Evolutionary rescue during extreme drought

Populations declining due to climate change may need to evolve to persist. While evolutionary rescue has been demonstrated in theory and the lab, its relevance to natural populations facing climate change remains unknown. Here we link rapid evolution and population dynamics in scarlet monkeyflower, Mimulus cardinalis, during an exceptional drought. We leverage whole-genome sequencing across 55 populations to identify climate-associated loci. Simultaneously we track demography and allele frequency change throughout the drought. We establish range-wide population decline during the drought, geographically variable rapid evolution, and variable population recovery that is predictable by standing genetic variation in and rapid evolution at climate-associated loci. These findings demonstrate evolutionary rescue in the wild, showing that genetic variation at adaptive, but not neutral loci, predicts population recovery.

evolutionary biology↗

bioRxiv2022

Poly(2-oxazoline)-based polyplexes as a PEG-free plasmid DNA delivery platform

The present study expands the versatility of cationic poly(2-oxazoline) (POx) copolymers as a PEG-free platform for gene delivery to immune cells, such as monocytes and macrophages. Several block copolymers are developed by varying non-ionic hydrophilic blocks (poly(2-methyl-2-oxazoline) (pMeOx) or poly(2-ethyl-2-oxazoline) (pEtOx), cationic blocks, and an optional hydrophobic block (poly(2-isopropyl-2-oxazoline) (iPrOx). The cationic blocks are produced by side chain modification of 2-methoxy-carboxyethyl-2-oxazoline (MestOx) block precursor with diethylenetriamine (DET) or tris(2-aminoethyl)amine (TREN). For the attachment of a targeting ligand, mannose, we employed azide-alkyne cycloaddition click chemistry methods. Of the two cationic side chains, polyplexes made with DET-containing copolymers transfect macrophages significantly better than those made with TREN-based copolymer. Likewise, non-targeted pEtOx-based diblock copolymer is more active in cell transfection than pMeOx-based copolymer. The triblock copolymer with hydrophobic block iPrOx performs poorly compared to the diblock copolymer which lacks this additional block. Surprisingly, attachment of a mannose ligand to either of these copolymers is inhibitory for transfection. Despite similarities in size and design, mannosylated polyplexes result in lower cell internalization compared to non-mannosylated polyplexes. Thus, PEG-free, non-targeted DET- and pEtOx-based diblock copolymer outperforms other studied structures in the transfection of macrophages and displays transfection levels comparable to GeneJuice, a commercial non-lipid transfection reagent.

bioengineering↗

bioRxiv2022

The locus coeruleus broadcasts prediction errors across the cortex to promote sensorimotor plasticity

Prediction errors are differences between expected and actual sensory input and are thought to be key computational signals that drive learning related plasticity. One way that prediction errors could drive learning is by activating neuromodulatory systems to gate plasticity. The catecholaminergic locus coeruleus (LC) is a major neuromodulatory system involved in neuronal plasticity in the cortex. Using two-photon calcium imaging in mice exploring a virtual environment, we found that the activity of LC axons in the cortex correlated with the magnitude of unsigned visuomotor prediction errors. LC response profiles were similar in both motor and visual cortical areas, indicating that LC axons broadcast prediction errors throughout the dorsal cortex. While imaging calcium activity in layer 2/3 of the primary visual cortex, we found that optogenetic stimulation of LC axons facilitated learning of a stimulus-specific suppression of visual responses during locomotion. This plasticity - induced by minutes of LC stimulation - recapitulated the effect of visuomotor learning on a scale that is normally observed during visuomotor development across days. We conclude that prediction errors drive LC activity, and that LC activity facilitates sensorimotor plasticity in the cortex, consistent with a role in modulating learning rates.

neuroscience↗

bioRxiv2022

Azithromycin possesses biofilm-inhibitory activity and potentiates non-bactericidal colistin methanesulfonate against Klebsiella pneumonia

Novel antibiotic combinations may act synergistically to inhibit the growth of multidrug-resistant bacterial pathogens but predicting which will be successful is difficult, and standard antimicrobial susceptibility testing may not identify important physiological differences between planktonic free-swimming and biofilm-protected surface-attached sessile cells. Using a nominally macrolide-resistant model Klebsiella pneumoniae strain (ATCC 10031) we demonstrate the effectiveness of several macrolides in inhibiting biofilm growth in multi-well plates, and the ability of azithromycin (AZM) to improve the effectiveness of the antibacterial last-agent-of-choice for K. pneumoniae infections, colistin methanesulfonate (CMS), against biofilms. This synergistic action was also seen in biofilm tests of several K. pneumoniae hospital isolates and could also be identified in polymyxin B disc-diffusion assays on azithromycin plates. Our work highlights the complexity of antimicrobial-resistance in bacterial pathogens and the need to test antibiotics with biofilm models where potential synergies might provide new therapeutic opportunities not seen in liquid culture or colony-based assays.

microbiology↗

bioRxiv2022

Locomotion-induced gain of visual responses cannot explain visuomotor mismatch responses in layer 2/3 of primary visual cortex

The aim of this work is to provide a comment on a recent paper by Muzzu and Saleem (2021). In brief, our concern is that the authors claim that visuomotor mismatch responses in mouse visual cortex can be explained by a locomotion-induced gain of visual halt responses, without directly comparing these responses to mismatch responses. Without a direct comparison, the claim that one response can explain the other appears difficult to uphold, more so because previous work finds that a uniform locomotion-induced gain cannot explain mismatch responses. To support these arguments, we analyzed a series of layer 2/3 calcium imaging datasets and show that coupling between visual flow and locomotion greatly enhances mismatch responses in an experience dependent manner compared to halts in non-coupled visual flow. This is consistent with mismatch responses representing visuomotor prediction errors. Thus, we conclude that feature selectivity cannot explain mismatch responses in mouse visual cortex.

neuroscience↗

bioRxiv2021

One mucosal administration of a live attenuated recombinant COVID-19 vaccine protects non-human primates from SARS-CoV-2

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 global pandemic. SARS-CoV-2 is an enveloped RNA virus that relies on its trimeric surface glycoprotein, spike, for entry into host cells. Here we describe the COVID-19 vaccine candidate MV-014-212, a live attenuated, recombinant human respiratory syncytial virus (RSV) expressing a chimeric SARS-CoV-2 spike as the only viral envelope protein. MV-014-212 was attenuated and immunogenic in African green monkeys (AGMs). One mucosal administration of MV-014-212 in AGMs protected against SARS-CoV-2 challenge, reducing by more than 200- fold the peak shedding of SARS-CoV-2 in the nose. MV-014-212 elicited mucosal immunity in the nose and neutralizing antibodies in serum that exhibited cross-neutralization against two virus variants of concern. Intranasally delivered, live attenuated vaccines such as MV-014-212 entail low-cost manufacturing suitable for global deployment. MV-014-212 is currently in phase 1 clinical trials as a single-dose intranasal COVID-19 vaccine.

immunology↗

bioRxiv2020

Regarding the F-word: the effects of data Filtering on inferred genotype-environment associations

Genotype-environment association (GEA) methods have become part of the standard landscape genomics toolkit, yet, we know little about how to filter genotype-by-sequencing data to provide robust inferences for environmental adaptation. In many cases, default filtering thresholds for minor allele frequency and missing data are applied regardless of sample size, having unknown impacts on the results. These effects could be amplified in downstream predictions, including management strategies. Here, we investigate the effects of filtering on GEA results and the potential implications for adaptation to environment. Using empirical and simulated datasets derived from two widespread tree species to assess the effects of filtering on GEA outputs. Critically, we find that the level of filtering of missing data and minor allele frequency affect the identification of true positives. Even slight adjustments to these thresholds can change the rate of true positive detection. Using conservative thresholds for missing data and minor allele frequency substantially reduces the size of the dataset, lessening the power to detect adaptive variants (i.e. simulated true positives) with strong and weak strength of selections. Regardless, strength of selection was a good predictor for GEA detection, but even SNPs under strong selection went undetected. We further show that filtering can significantly impact the predictions of adaptive capacity of species in downstream analyses. We make several recommendations regarding filtering for GEA methods. Ultimately, there is no filtering panacea, but some choices are better than others, depending largely on the study system, availability of genomic resources, and desired objectives of the study.

genomics↗

bioRxiv2020

Opposing influence of top-down and bottom-up input on different types of excitatory layer 2/3 neurons in mouse visual cortex

Processing in cortical circuits is driven by combinations of cortical and subcortical inputs. These signals are often conceptually categorized as bottom-up input, conveying sensory information, and top-down input, conveying contextual information. Using intracellular recordings in mouse visual cortex, we measured neuronal responses to visual input, locomotion, and visuomotor mismatches. We show that layer 2/3 (L2/3) neurons compute a difference between top-down motor-related input and bottom-up visual flow input. Most L2/3 neurons responded to visuomotor mismatch with either hyperpolarization or depolarization, and these two response types were associated with distinct physiological properties. Consistent with a subtraction of bottom-up and top-down input, visual and motor-related inputs had opposing influence in L2/3 neurons. In infragranular neurons, we found no evidence of a difference-computation and responses were consistent with a positive integration of visuomotor inputs. Our results provide evidence that L2/3 functions as a bidirectional comparator of top-down and bottom-up input.

neuroscience↗

bioRxiv2018

Homing and egg discrimination in the Western Slimy Salamander, Plethodon albagula (Caudata: Plethodontidae)

In some species of vertebrates egg brooding is a costly form of parental care. Therefore, misdirection of parental care can significantly lower a females fitness. Because of the maternal investment and increased survivorship to offspring from egg guarding, a brooding female should home to her nest site after being displaced a short distance and discriminate between her own eggs and eggs from other females. In this study, we experimentally tested, in the field, alternative hypotheses concerning homing ability and egg discrimination in a population of nesting western slimy salamanders (Plethodon albagula). Fourteen brooding females were displaced 1 m to the left or right of their nest sites (determined randomly) for the homing experiment. Furthermore, brooding females (n = 13) were presented with their own clutches, which were displaced 50 cm to the left or right (determined randomly), and unfamiliar egg clutches at their original nest sites. The females were released at an equal distance from both egg clutches. After 24 hours, 12 displaced females (86%) had returned to their own nest sites and were brooding their egg clutches. Also, after 24 hours, nine test females had returned to their own nest sites and were brooding the unfamiliar egg clutches. No control or test females were present at the other new nest site locations. Therefore, we suggest that brooding female P. albagula do home to their nest sites and exhibit indirect egg discrimination.

animal behavior and cognition↗

bioRxiv2017

Sniff-invariant intensity perception using olfactory bulb coding of inhalation dynamics

For stable perception of odor intensity, there must exist a neural correlate that is invariant across other parameters, such as the highly variable sniff cycle. Previous hypotheses suggest that variance in inhalation dynamics alters odor concentration profiles in the naris despite a constant environmental concentration. Using whole cell recordings in the olfactory bulb of awake mice, we directly demonstrate that increased sniffing frequency mimics the effect of odor concentration increase at the level of both mitral and tufted cell (MTC) firing rate responses and temporal responses. In contrast, we find that mice are capable of discriminating concentrations within short timescales despite highly variable sniffing behavior. We reason that the only way mice can differentiate a change in sniff parameters and a change in concentration is to encode information about the inhalation parameters in parallel. While conceivably this could be achieved via corollary discharge from respiration control centres, we find that the sniff-driven activity of MTCs without odor input is informative of the kind of inhalation that just occurred, allowing rapid detection of a change in inhalation. Thus, a possible reason for sniff modulation of the early olfactory system may be to inform downstream centres of nasal flow dynamics, so that an inference can be made about environmental concentration independent of sniff variance.

neuroscience↗

bioRxiv2017

Active sampling state dynamically enhances olfactory bulb odor representation

The olfactory bulb (OB) is the very first site of odor information processing, yet a wealth of contextual and learned information has been described in its activity. To investigate the mechanistic basis of contextual modulation, we use whole-cell recordings to measure odor responses across rapid (<30 min) learning episodes in identified mitral/tufted cells (MTCs). Across these learning episodes, we found that diverse response changes occur already during the first sniff cycle. Motivated mice develop active sniffing strategies across learning, and it is this change of active sampling state that dynamically modulates odor responses, resulting in enhanced discriminability and detectability of odor representation with learning. Evoking fast sniffing in different behavioral states demonstrates that response changes during active sampling exceed those predicted from purely feed-forward input. Finally, response changes are highly correlated in tufted cells, but not mitral cells, indicating cell-type specificity in the effect of active sampling, and resulting in increased odor detectability in the tufted and enhanced discriminability in the mitral cell population over the rapid learning episodes. Altogether, we show that active sampling state is a crucial component in modulating and enhancing olfactory bulb responsiveness on rapid timescales.

neuroscience↗