Biology subjects

Springer, K.

Publications and source records attributed to Springer, K..

4 recordsLinked to original sources

bioRxiv2025

HCN channel currents underlie distinct neurophysiology of mediodorsal thalamus subnuclei

The mediodorsal thalamus (MD) is a hub coordinating cortical and subcortical brain regions to support executive and social/emotional functioning. MD can be subdivided into medial (M), central (C), and lateral (L) based on synaptic coupling, molecular identity, and physiology. Recently, we identified differential intrinsic properties between thalamocortical M and L neurons projecting to the medial prefrontal cortex (mPFC). L neurons projecting to mPFC showed increased hyperpolarization activated cyclic nucleotide gated (HCN) channel activity compared with M neurons, which caused L neurons to have lower cellular resistance and shorter time windows for integration of inputs. In addition to their role in synaptic integration, HCN channels are critical for thalamic rhythm generation. In this study, we used a combination of patch clamp electrophysiology and in situ hybridization to investigate how differences in HCN impact intrinsic oscillatory dynamics in M, C, and L neurons. We found that HCN current differed across MD subnuclei with C > L >> M. Clustering neurons based on HCN properties was sufficient to classify subnuclei with >95% accuracy, highlighting the differences in HCN function between subnuclei. Greater HCN activity in MD neurons was associated with decreased input resistance, decreased action potential firing, and higher resonant frequency. These findings provide an ionic basis for differences in cellular resonance across MD subnuclei, with implications for thalamic rhythm generation and information processing.

neuroscience↗

bioRxiv2024

Old, deciduous stands support both high biodiversity and carbon storage in German forests

Ecosystems worldwide face threats related to human-driven degradation, climate change, and biodiversity loss. Addressing these challenges requires management strategies that combine biodiversity conservation with climate change mitigation. Here, we aimed to identify local-scale management actions that promote biodiversity at multiple trophic levels while also promoting carbon storage and sequestration. We combined data on the diversity of nine taxonomic groups (plants, birds, moths, Mollusca, soil fungi, active soil bacteria, Cercozoan and Endomyxan soil protists, Oomycotan soil protists, and nematodes), with above- and belowground carbon storage in 150 temperate forest plots in three regions of Germany. These were dominated by European beech, pine, spruce and oak. We investigated the relationships between multiple forest structure and management variables, biodiversity and carbon storage and sequestration in forest plots with different management types. Carbon storage was 32% higher in uneven-aged than even-aged forests and increased with mean tree diameter, while carbon sequestration in trees was 15% higher in even-aged than uneven-aged stands. Mean tree diameter was positively related to overall biodiversity, especially bird species richness and the richness of forest specialist birds. Oak and beech-dominated stands harboured higher biodiversity than stands dominated by conifers (especially Pine). One exception to this was the richness of plant species and forest specialist plants, which were highest in spruce plantations. Surprisingly, deadwood input did not significantly affect the diversity of any taxonomic group in this study. By showing that older forests with a high proportion of uneven-aged broad-leafed trees, or oak-dominated forests, can promote both biodiversity and carbon storage, our results could help inform sustainable local-scale forest management in Central Europe that promotes both biodiversity conservation and carbon storage. These findings can form the basis of further larger-scale studies investigating such relations at larger spatial scales to inform landscape-level recommendations for sustainable multifunctional forest management.

ecology↗

bioRxiv2024

Plural molecular and cellular mechanisms of pore domain KCNQ2 encephalopathy

KCNQ2 variants in children with neurodevelopmental impairment are difficult to assess due to their heterogeneity and unclear pathogenic mechanisms. We describe a child with neonatal-onset epilepsy, developmental impairment of intermediate severity, and KCNQ2 G256W heterozygosity. Analyzing prior KCNQ2 channel cryoelectron microscopy models revealed G256 as a node of an arch-shaped non-covalent bond network linking S5, the pore turret, and the ion path. Co-expression with G256W dominantly suppressed conduction by wild-type subunits in heterologous cells. Ezogabine partly reversed this suppression. G256W/+ mice have epilepsy leading to premature deaths. Hippocampal CA1 pyramidal cells from G256W/+ brain slices showed hyperexcitability. G256W/+ pyramidal cell KCNQ2 and KCNQ3 immunolabeling was significantly shifted from axon initial segments to neuronal somata. Despite normal mRNA levels, G256W/+ mouse KCNQ2 protein levels were reduced by about 50%. Our findings indicate that G256W pathogenicity results from multiplicative effects, including reductions in intrinsic conduction, subcellular targeting, and protein stability. These studies provide evidence for an unexpected and novel role for the KCNQ2 pore turret and introduce a valid animal model of KCNQ2 encephalopathy. Our results, spanning structure to behavior, may be broadly applicable because the majority of KCNQ2 encephalopathy patients share variants near the selectivity filter.

neuroscience↗

bioRxiv2020

Cellular taxonomy and spatial organization of the ventral posterior hypothalamus reveals neuroanatomical parcellation of the mammillary bodies

The ventral posterior hypothalamus (VPH) is an anatomically complex brain region implicated in arousal, reproduction, energy balance and memory processing. However, neuronal cell type diversity within the VPH is poorly understood, an impediment to deconstructing the roles of distinct VPH circuits in physiology and behavior. To address this question, we employed a droplet-based single cell RNA sequencing (scRNA-seq) approach to systematically classify molecularly distinct cell types in the mouse VPH. Analysis of >16,000 single cells revealed 20 neuronal and 18 non-neuronal cell populations, defined by suites of discriminatory markers. We validated differentially expressed genes in a selection of neuronal populations through fluorescence in situ hybridization (FISH). Focusing on the mammillary bodies (MB), we discovered transcriptionally-distinct clusters that exhibit a surprising degree of segregation within neuroanatomical subdivisions of the MB, while genetically-defined MB cell types project topographically to the anterior thalamus. This single cell transcriptomic atlas of cell types in the VPH provides a detailed resource for interrogating the circuit-level mechanisms underlying the diverse functions of VPH circuits in health and disease.

neuroscience↗