Biology subjects

Franzelin, A.

Publications and source records attributed to Franzelin, A..

5 recordsLinked to original sources

bioRxiv2025

Mapping prefrontal afferents along development

The medial prefrontal cortex (mPFC) acts as a hub for cognitive, emotional, and social processes, integrating neuronal inputs from numerous brain regions. Knowledge on the processes underlying formation and myelination of prefrontal afferents is essential for a comprehensive understanding of the emergence, maturation, and refinement of mPFC-dependent behaviors. However, despite detailed investigation of long-range projections to the mPFC in the adult brain, little is known about their maturation. Here, we use retrograde labeling, light-sheet imaging, and automatic cell segmentation to quantify afferent projections to the mPFC from neonatal to adult age. We show that densities of ipsi- and contralateral prefrontal afferents change along development from a widespread bilateral distribution at neonatal age to a predominantly ipsilateral organization. Furthermore, myelination of interhemispheric prefrontal afferents starts only after the decline of neonatal contralateral projections and is followed by temporally elevated projection densities from limbic brain regions. Overall, these distinct developmental dynamics of prefrontal afferents might have major implications for the maturation of mPFC-dependent functional and behavioral outputs.

neuroscience↗

bioRxiv2024

Epigenetic repression of cFos supports sequential formation of distinct spatial memories

Expression of the immediate early gene cFos modifies the epigenetic landscape of activated neurons with downstream effects on synaptic plasticity. The production of cFos is inhibited by a long-lived isoform of another Fos family gene, {Delta}FosB. It has been speculated that this negative feedback mechanism may be critical for protecting episodic memories from being overwritten by new information. Here, we investigate the influence of {Delta}FosB inhibition on cFos expression and memory. Hippocampal neurons in slice culture produce more cFos on the first day of stimulation compared to identical stimulation on the following day. This downregulation affects all hippocampal subfields and requires histone deacetylation. Overexpression of {Delta}FosB in individual pyramidal neurons effectively suppresses cFos, indicating that accumulation of {Delta}FosB is the causal mechanism. Water maze training of mice over several days leads to accumulation of {Delta}FosB in granule cells of the dentate gyrus, but not in CA3 and CA1. Because the dentate gyrus is thought to support pattern separation and cognitive flexibility, we hypothesized that inhibiting the expression of {Delta}FosB would affect reversal learning, i.e., the ability to successively learn new platform locations in the water maze. The results indicate that pharmacological HDAC inhibition, which prevents cFos repression, impairs reversal learning, while learning and memory of the initial platform location remain unaffected. Our study supports the hypothesis that epigenetic mechanisms tightly regulate cFos expression in individual granule cells to orchestrate the formation of time-stamped memories.

neuroscience↗

bioRxiv2023

Neuronal FOS reports synchronized activity of presynaptic neurons

The immediate early gene FOS is frequently used as a marker for highly active neurons. Implicit in this use is the assumption that there is a correlation between neuronal spiking and FOS expression. Here we use optogenetic stimulation of hippocampal neurons to investigate the relation between spike frequency and FOS expression, and report several surprising observations. First, FOS expression is cell-type specific, spiking CA2 pyramidal neurons rarely express FOS. Second, FOS has a U-shaped dependence on frequency: Spiking at 0.1 Hz is more effective than high frequency spiking (50 Hz) while intermediate frequencies do not induce FOS. Third, the pathway from spiking to FOS is not cell-autonomous. Instead, transmitter release and metabotropic glutamate receptor (mGluR) activation are required and, at 0.1 Hz, FOS is induced independently of CREB/calcineurin/MEK pathways. We propose that FOS does not primarily encode a neurons own spike frequency but indicates repeated participation in highly synchronized activity, e.g. sharp wave ripples.

neuroscience↗

bioRxiv2020

Freeze-frame imaging of dendritic calcium signals with TubuTag

The extensive dendritic arbor of neurons is thought to be actively involved in the processing of information. Dendrites contain a rich diversity of ligand- and voltage-activated ion channels as well as metabotropic receptors. In addition, they are capable of releasing calcium from intracellular stores. Under specific conditions, large neurons produce calcium spikes that are locally restricted to a dendritic section. To investigate calcium signaling in dendrites, we introduce TubuTag, a genetically encoded calcium sensor anchored to the cytoskeleton. TubuTag integrates cytoplasmic calcium signals by irreversible photoconversion from green to red fluorescence when illuminated with violet light. To image the mm-long dendritic tree of pyramidal neurons at subcellular resolution, we used a custom two-photon microscope with a large field of view. As the read-out of fluorescence can be performed several hours after photoconversion, TubuTag will help investigating dendritic signal integration and calcium homeostasis in large populations of neurons.

neuroscience↗

bioRxiv2020

cFos ensembles in the dentate gyrus rapidly segregate over time and do not form a stable map of space

Transgenic cFos reporter mice are used to identify and manipulate neurons that store contextual information during fear learning. It is not clear, however, how spatial information acquired over several training days is integrated in the hippocampus. Using a water maze task, we observed that cFos expression patterns in the dentate gyrus are temporally unstable and shift daily. Surprisingly, cFos patterns did not get more stable with increasing spatial memory precision. Despite the fact that cFos was no longer expressed, optogenetic inhibition of neurons that expressed cFos on the first training day affected performance days later. Triggered by training, {Delta}FosB accumulates and provides a negative feedback mechanism that makes the cFos ensemble in the dentate gyrus dependent on the history of activity. Shifting cFos expression to a different set of granule cells every day may aid the formation of episodic memories.

neuroscience↗