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Berry, J. A.

Publications and source records attributed to Berry, J. A..

2 recordsLinked to original sources
bioRxiv2026

Proximity labelling of D1-like dopamine receptors reveals distinct cellular environments and uncovers trafficking proteins that regulate DA mediated behaviors in Drosophila

The neurotransmitter dopamine (DA) is central to synaptic regulation that support diverse behavioral functions, including both learning and forgetting. This multi-functional role of DA is due to receptor specific signaling in specific subcellular environments that remain uncharacterized. Here we utilized proximity labelling proteomics in human cells to characterize the proximal environments of two Drosophila D1-like DA receptors (Dop1R1 and Dop1R2) in basal and DA activation environments. While DA drives both receptors to recruit Beta-Arrestin 2, Dop1R1 alone showed ligand driven recruitment of G-protein Receptor Kinase 2/3, proximity to clathrin mediated endocytosis, and WASH complex mediated endosomal trafficking. Additionally, we show evidence that Dop1R1 and Dop1R2 reside in distinct domains at the cell surface. In vivo disruption of Drosophila orthologs of Dop1R proximal proteins revealed three trafficking proteins, Sec24AB, Krz, and CG13887, that regulate R1-mediated learning, starvation induced attraction to odors, and DA-mediated cAMP responses in memory circuits. In addition to revealing DA receptor trafficking proteins that support learning, our comparative characterization of the cellular environments D1-like receptors offers insights into how DA differentially regulates diverse behavioral and synaptic functions. For TOC only O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/728438v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@656e56org.highwire.dtl.DTLVardef@12f0084org.highwire.dtl.DTLVardef@cb05cdorg.highwire.dtl.DTLVardef@e9d623_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗
bioRxiv2025

Anesthesia-triggered dopaminergic bursts actively induce forgetting: a paradigm shift in understanding cold-shock amnesia

Retrograde memory loss, the inability to recall events preceding amnesia onset, is a well-documented consequence of anesthesia. Recent discoveries, pioneered by Drosophila research, have challenged the view that forgetting is a passive process, and have demonstrated that rather it is a highly active, well-regulated biological process. This work builds on this and makes a remarkable and unexpected discovery that anesthesia itself triggers a robust, widespread burst of activity in dopaminergic neurons. Here, we report that both cold-shock and CO2 anesthesia elicits strong activation in PAM and PPL1 dopaminergic neuron populations. This calcium activity is accompanied by robust synaptic release of dopamine. Strikingly, pharmacological experiments show that this response is input-driven, as it is completely abolished by Na+ channel blockers and dampened by nAChR antagonists. Using behavioral methods, crucially, we show that anesthesia-induced amnesia can be prevented by blocking activity in PAM and PPL1 neurons during anesthesia. Together, our findings reveal a previously unrecognized active mechanism by which anesthesia induces forgetting, mediated by rapid dopaminergic signaling. This paradigm-shifting discovery redefines how we think about anesthesia-induced amnesia and the biology of forgetting.

neuroscience↗