Biology subjects

Dieter, A.

Publications and source records attributed to Dieter, A..

5 recordsLinked to original sources

bioRxiv2026

Disruption of the Brain-Spleen Axis Impairs Monocyte-Microglia Communication and Accelerates Disease Progression in a Model of Amyloidosis

Alzheimers disease (AD) is characterized by a prolonged asymptomatic phase before cognitive decline emerges, yet the mechanisms driving symptom onset remain unclear. Here, we hypothesized that the transition from asymptomatic to symptomatic disease is linked to dysfunction of brain-immune communication. Retrograde neuronal tracing in the 5xFAD mouse model of amyloidosis revealed reduced brain-spleen connectivity at advanced disease stages. To probe the functional role of the brain-spleen axis in coping with disease, we denervated the splenic nerve at an early presymptomatic stage. This intervention accelerated cognitive decline, impaired splenic hematopoiesis, diminished monocyte recruitment to the brain, disrupted monocyte-microglia signaling networks, and reduced the transition of microglia from a homeostatic to the disease-associated (DAM) state. Conversely, enhancing splenic noradrenergic input increased hematopoiesis, restored monocyte homing to the brain, and delayed cognitive impairment. The protective role of splenic monocytes was independently validated in a retinal cytotoxic injury model, in which splenic denervation impaired post-insult retinal ganglion cell survival. Together, these findings identify an active brain-spleen circuit in regulating monocyte recruitment and establish peripheral monocytes as key drivers of microglial state transitions and disease progression.

neuroscience↗

bioRxiv2022

A flexible and versatile system for multicolor fiber photometry and optogenetic manipulation

Fiber photometry is a technique of growing popularity in neuroscientific research. It is widely used to infer brain activity by recording calcium dynamics in genetically defined populations of neurons. Aside from the wide variety of calcium indicators, other genetically encoded biosensors have recently been engineered to measure membrane potential, neurotransmitter release, pH, or various cellular metabolites, such as ATP or cAMP. Due to the spectral characteristics of these molecular tools, different assemblies of optical hardware are usually needed to reveal the full potential of different biosensors. In addition, the combination of multiple biosensors in one experiment often requires the investment in more complex equipment, which limits the flexibility of the experimental design. Such constraints often hamper a straightforward implementation of new molecular tools, evaluation of their performance in vivo, and design of new experimental paradigms - especially if the financial budget is a limiting factor. Here, we propose a novel approach for fiber photometry recordings, based on a multimode optical fused-fiber coupler (FFC) for both light delivery and collection. Recordings can readily be combined with optogenetic manipulations in a single device without the requirement for dichroic beam-splitters. In combination with a multi-color light source and appropriate emission filters, our approach offers remarkable flexibility in experimental design and facilitates the implication of new molecular tools in vivo at minimal cost. The ease of assembly, operation, characterization, and customization of this platform holds the potential to foster the development of experimental strategies for multicolor fused fiber photometry (FFP) combined with optogenetics far beyond its current state. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=186 SRC="FIGDIR/small/484590v1_ufig1.gif" ALT="Figure 1"> View larger version (45K): org.highwire.dtl.DTLVardef@13abbdcorg.highwire.dtl.DTLVardef@10384d7org.highwire.dtl.DTLVardef@67938org.highwire.dtl.DTLVardef@1005aee_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIFused Fiber Photometry (FFP) enables straightforward monitoring and manipulation of brain activity C_LIO_LIFFP allows monitoring of indicators with virtually any spectral characteristics C_LIO_LIFFP is compatible with simultaneous optogenetic manipulation C_LIO_LIEasy assembly, characterization, and customization C_LI

neuroscience↗

bioRxiv2022

Targeting Noradrenergic Neurons of the Locus Coeruleus: A Comparison of Model Systems and Strategies

The locus coeruleus (LC) norepinephrine (NE) system is involved in a variety of physiological and pathophysiological processes. Refining our understanding of LC function largely relies on selective transgene expression in LC-NE neurons, allowing targeted manipulation and readout of noradrenergic neurons. Here, we performed a side-by-side comparison of the most commonly used strategies to genetically target the LC, including different cre driver lines and promoter-mediated transgene expression. We report differences between these strategies in terms of transgene expression efficacy and specificity. Parallelly, we found no behavioral alterations in cre-expressing mice of any mouse line compared to wild-type littermates. Finally, to further facilitate the investigation of LC-NE function, we created a suite of constructs, including a reporter protein, a calcium indicator, and a light-driven cation channel, whose expression is mediated by the previously described PRSx8 promoter. These constructs allow identification, monitoring, and manipulation of LC-NE activity either in wild-type mice, or in combination with tissue-specific manipulations of different cre driver lines. The results of our study are crucial for the interpretation of previous experiments using the respective targeting strategies, as well as for the design of future studies. BlurbThis study reports substantial heterogeneity in transgene expression patterns when using different strategies to virally transduce noradrenergic neurons of the locus coeruleus, highlighting the need to carefully validate each experimental approach in order to avoid misinterpretations when studying locus coeruleus function. Highlights- Heterogeneous expression patterns with different targeting strategies for LC-NE neurons - Substantial ectopic transgene expression observed in some approaches - No behavioral alterations in heterozygous cre mice as compared to wild-types - PRSx8-driven reporters, indicators and actuators as a resource to investigate LC function

neuroscience↗

bioRxiv2020

BiPOLES: a tool for bidirectional dual-color optogenetic control of neurons

Optogenetic manipulation of neuronal activity has become an indispensable experimental strategy in neuroscience research. A large repertoire of excitatory and inhibitory tools allows precise activation or inhibition of genetically targetable neuronal populations. However, an optogenetic tool for reliable bidirectional control of neuronal activity allowing both up- and downregulation of the same neurons in a single experiment is still missing. Here we report BiPOLES, an optogenetic tool for potent excitation and inhibition of the same population of neurons with light of two different colors. BiPOLES consists of an inhibitory, blue-light-sensitive anion-conducting channelrhodopsin fused to an excitatory, red-light-sensitive cation-conducting channelrhodopsin in a single, trafficking-optimized tandem protein. BiPOLES enables multiple new applications including potent dual-color spiking and silencing of the same neurons in vivo and dual-color optogenetic control of two independent neuronal populations.

neuroscience↗

bioRxiv2020

Hearing restoration by a low-weight power-efficient multichannel optogenetic cochlear implant system

In case of deafness, electrical cochlear implants (eCIs) bypass dysfunctional or lost hair cells by direct stimulation of the auditory nerve. However, spectral selectivity of eCI sound coding is low as the wide current spread from each electrode activates large sets of neurons along the tonotopic axis. As light can be better confined in space, optical cochlear implants (oCIs) promise to overcome this shortcoming of eCIs. This requires appropriate sound processing and control of multiple microscale emitters. Here, we describe the development, characterisation, and application of a preclinical low-weight and wireless LED-based multichannel oCI system for hearing restoration and its companion to its sister eCI system. The head-worn oCI system enabled deafened rats to perform a locomotion task in response to acoustic stimulation proving the concept of multichannel optogenetic hearing restoration in rodents.

neuroscience↗