Biology subjects

Rowan, M.

Publications and source records attributed to Rowan, M..

6 recordsLinked to original sources

bioRxiv2026

Projection populations form a dorsoventral gradient of reward representations in the lateral septum

Several decades ago, the septal region was identified as the most dependable location of intracranial self-stimulation (ICSS) in the brain, but the neural substrates that mediate septal self-stimulation are still unknown. One part of the septal region, the lateral septum (LS), contributes to a number of motivated behaviors and may promote reward-seeking. However, the LS contains different anatomical subregions, complicating the characterization of its reward representations. We examine the responses of LS neurons along its dorsoventral axis using cellular resolution calcium imaging during an operant assay. We find that a greater proportion of neurons are excited in response to sucrose reward in the dorsal LS, while a greater proportion are inhibited in response to sucrose reward in the ventral LS. Additionally, we identify two distinct LS projection populations, one to the nucleus accumbens (NAc) and another to the bed nucleus of the stria terminalis (BNST), which are located in the dorsal and ventral regions of the LS, respectively. These two projection populations also have opposing reward responses and their corresponding optogenetic manipulation supports ICSS. These findings demonstrate how LS projection populations contribute to its functional heterogeneity, especially as it pertains to reward-seeking behavior.

neuroscience↗

bioRxiv2023

Native-state proteomics of Parvalbumin interneurons identifies novel molecular signatures and metabolic vulnerabilities to early Alzheimer's disease pathology

One of the earliest pathophysiological perturbations in Alzheimers Disease (AD) may arise from dysfunction of fast-spiking parvalbumin (PV) interneurons (PV-INs). Defining early protein-level (proteomic) alterations in PV-INs can provide key biological and translationally relevant insights. Here, we use cell-type-specific in vivo biotinylation of proteins (CIBOP) coupled with mass spectrometry to obtain native-state proteomes of PV interneurons. PV-INs exhibited proteomic signatures of high metabolic, mitochondrial, and translational activity, with over-representation of causally linked AD genetic risk factors. Analyses of bulk brain proteomes indicated strong correlations between PV-IN proteins with cognitive decline in humans, and with progressive neuropathology in humans and mouse models of A{beta} pathology. Furthermore, PV-IN-specific proteomes revealed unique signatures of increased mitochondrial and metabolic proteins, but decreased synaptic and mTOR signaling proteins in response to early A{beta} pathology. PV-specific changes were not apparent in whole-brain proteomes. These findings showcase the first native state PV-IN proteomes in mammalian brain, revealing a molecular basis for their unique vulnerabilities in AD.

neuroscience↗

bioRxiv2023

A novel enhancer-AAV approach selectively targeting dentate granule cells

The mammalian brain contains the most diverse array of cell types of any organ, including dozens of neuronal subtypes with distinct anatomical and functional characteristics. The brain leverages these neuron-type-specializations to perform diverse circuit operations and thus execute different behaviors properly. Through the use of Cre lines, access to specific neuron types has steadily improved over past decades. Despite their extraordinary utility, development and cross-breeding of Cre lines is time-consuming and expensive, presenting a significant barrier to entry for many investigators. Furthermore, cell-based therapeutics developed in Cre mice are not clinically translatable. Recently, several AAV vectors utilizing neuron-type-specific regulatory transcriptional sequences (enhancer-AAVs) were developed which overcome these limitations. Using a publicly available RNAseq dataset, we evaluated the potential of several candidate enhancers for neuron-type-specific targeting in the hippocampus. Here we identified a promising enhancer-AAV for targeting dentate granule cells and validated its selectivity in wild-type adult mice.

neuroscience↗

bioRxiv2022

A reproducible and tunable synthetic soil microbial community provides new insights into microbial ecology

Microbial soil communities form commensal relationships with plants to promote the growth of both parties. Optimization of plant-microbe interactions to advance sustainable agriculture is an important field in agricultural research. However, investigation in this field is hindered by a lack of model microbial community systems and efficient approaches for building these communities. Two key challenges in developing standardized model communities are maintaining community diversity over time and storing/resuscitating these communities after cryopreservation, especially considering the different growth rates of organisms. Here, a model community of 17 soil microorganisms commonly found in the rhizosphere of diverse plant species, isolated from soil surrounding a single switchgrass plant, has been developed and optimized for use with fabricated ecosystem devices (EcoFABs). EcoFABs allow reproducible research in model plant systems, with precise control of environmental conditions and easy measurement of plant-microbe metrics. The model soil community grows reproducibly in vitro between replicates and experiments, with high community -diversity achieved through growth in low-nutrient media and adjustment of starting composition ratios for the growth of individual organisms. The community additionally grows in EcoFAB devices and regrows with a similar composition to unfrozen communities following cryopreservation with glycerol, allowing for dissemination of the model community. Our results demonstrate the generation of a stable microbial community that can be used with EcoFAB devices and shared between research groups for maximum reproducibility. ImportanceMicrobes associate with plants in distinct soil communities, to the benefit of both the soil microbes and the plant. Interactions between plants and these microbes can improve plant growth and health and are therefore a field of study in sustainable agricultural research. In this study, a model community of 17 soil bacteria has been developed to further reproducible study of plant-soil microbe interactions. Preservation of the microbial community has been optimized for dissemination to other research settings. Overall, this work will advance soil microbe research through optimization of a robust, reproducible model community.

microbiology↗

bioRxiv2021

Lateralization of autonomic activity in response to limb-specific threat

In times of stress or danger, the autonomic nervous system (ANS) signals the fight or flight response. A canonical function of ANS activity is to globally mobilize metabolic resources, preparing the organism to respond to threat. Yet a body of research has demonstrated that, rather than displaying a homogenous pattern across the body, autonomic responses to arousing events -- as measured through changes in electrodermal activity (EDA) -- can differ between right and left body locations. Surprisingly, the metabolic function of such ANS asymmetry has not been investigated. In the current study, we investigated whether asymmetric autonomic responses could be induced through limb-specific aversive stimulation. Participants were given mild electric stimulation to either the left or right arm while EDA was monitored bilaterally. Across participants, a strong ipsilateral EDA response bias was observed, with increased EDA response in the hand adjacent to the stimulation. This effect was observable in over 50% of individual subjects. These results demonstrate that autonomic output is more complex than canonical interpretations suggest. We suggest that, in stressful situations, autonomic outputs can prepare either the whole-body fight or flight response, or a simply a limb-localized flick, which can effectively neutralize the threat while minimizing global resource consumption. These findings provide insight into the evolutionary pathway of neural systems processing general arousal by linking observed asymmetry in the peripheral arousal response to a historical leveraging of neural structures organized to mediate responses to localized threat.

neuroscience↗

bioRxiv2020

Hippocampal hyperactivity in a rat model of Alzheimers disease

Neuronal network dysfunction is a hallmark of Alzheimers disease (AD). However, the underlying pathomechanisms remain unknown. We analyzed the hippocampal micronetwork in a rat model of AD at an early disease stage at the beginning of extracellular amyloid beta (A{beta}) deposition. We established two-photon Ca2+-imaging in vivo in the hippocampus of rats and found hyperactivity of CA1 neurons. Patch-clamp recordings in brain slices in vitro revealed changes in the passive properties and intrinsic excitability of CA1 pyramidal neurons. Furthermore, we observed increased neuronal input resistance and prolonged action potential width in CA1 pyramidal neurons. Surprisingly, all parameters measured to quantify synaptic inhibition and excitation onto CA1 pyramidal neurons were intact suggesting a cell immanent deficit. Our data support the view that altered intrinsic excitability of CA1 neurons may precede inhibitory dysfunction at an early stage of disease progression.

neuroscience↗