Biology subjects

Dannehl, D.

Publications and source records attributed to Dannehl, D..

2 recordsLinked to original sources

bioRxiv2020

Single-dose ethanol intoxication causes acute and lasting neuronal changes in the brain

Alcohol intoxication at early ages is a risk factor for development of addictive behavior. To uncover neuronal molecular correlates of acute ethanol intoxication, we used stable-isotope labeled mice combined with quantitative mass spectrometry to screen over 2000 hippocampal proteins of which 72 changed synaptic abundance up to two-fold after ethanol exposure. Among those were mitochondrial proteins and proteins important for neuronal morphology, including MAP6 and Ankyrin-G. Based on these candidate proteins, we found acute and lasting molecular, cellular, and behavioral changes following a single intoxication in alcohol-naive mice. Immunofluorescence analysis revealed a shortening of axon initial segments. Longitudinal two-photon in vivo imaging showed increased synaptic dynamics and mitochondrial trafficking in axons. Knockdown of mitochondrial trafficking in dopaminergic neurons abolished conditioned alcohol preference in Drosophila. This introduces mitochondrial trafficking as a process implicated in reward learning, and highlights the potential of high-resolution proteomics to identify cellular mechanisms relevant for addictive behavior.

neuroscience↗

bioRxiv2020

Sensory input drives rapid homeostatic scaling of the axon initial segment in mouse barrel cortex

The axon initial segment (AIS) is an important axonal microdomain for action potential initiation and implicated in the regulation of neuronal excitability during activity-dependent cortical plasticity. While structural AIS plasticity has been suggested to fine-tune neuronal activity when network states change, whether it acts as a homeostatic regulatory mechanism in behaviorally relevant contexts remains poorly understood. Using an in vivo model of the mouse whisker-to-barrel pathway in combination with immunofluorescence, confocal analysis and patch-clamp electrophysiological recordings, we observed bidirectional AIS plasticity. Furthermore, we find that structural and functional AIS remodeling occurs in distinct temporal domains: long-term sensory deprivation elicits an AIS length increase, accompanied with an increase in neuronal excitability, while sensory enrichment results in a rapid AIS shortening, accompanied by a decrease in action potential generation. Our findings highlight a central role of the AIS in the homeostatic regulation of neuronal input-output relations.

neuroscience↗