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Gonzalez, L. S.

Publications and source records attributed to Gonzalez, L. S..

2 recordsLinked to original sources

Ventral striatal dopamine encodes unique properties of visual stimuli in mice

The mesolimbic dopamine system is an evolutionarily conserved set of brain circuits that plays a role in attention, appetitive behavior, and reward processing. In this circuitry, ascending dopaminergic projections from the ventral midbrain innervate targets throughout the limbic forebrain, such as the ventral striatum/nucleus accumbens (NAc). Dopaminergic signaling in the NAc has been widely studied for its role in behavioral reinforcement, reward prediction error encoding, and motivational salience. Less well characterized is the role of dopaminergic neurotransmission in the response to surprising or alerting sensory events. To address this, we used the genetically encoded dopamine sensor dLight1 and fiber photometry to explore the ability of striatal dopamine release in to encode the properties of salient sensory stimuli in mice, such as threatening looming discs. Here, we report that NAc lateral shell (LNAc) dopamine release encodes the rate and magnitude of environmental luminance changes rather than visual stimulus threat level. This encoding is highly sensitive, as LNAc dopamine could be evoked by light intensities that were imperceptible to human experimenters. We also found that light-evoked dopamine responses are wavelength-dependent at low irradiances, independent of the circadian cycle, robust to previous exposure history, and involve multiple phototransduction pathways. Thus, we have further elaborated the mesolimbic dopamine systems ability to encode visual information in mice, which is likely relevant to a wide body of scientists employing light sources or optical methods in behavioral research involving rodents.

neuroscience↗

Single Cell Transcriptomics identifies a WNT7A-FZD5 Signaling Axis that maintains Fallopian Tube Stem Cells in Patient-derived Organoids

Despite its significance to reproduction, fertility, sexually transmitted infections and various pathologies, the fallopian tube (FT) is relatively understudied. Strong evidence points to the FT as the tissue-of-origin of high grade serous ovarian cancer (HGSOC), the most fatal gynaecological malignancy. HGSOC precursor lesions arise specifically in the distal FT (fimbria) which is reported to be enriched in stem-like cells. Investigation of the role of FT stem cells in health and disease has been hampered by a lack of characterization of FT stem cells and lack of models that recapitulate stem cell renewal and differentiation in vitro. Using optimized organoid culture conditions to address these limitations, we found that FT stem cell renewal is highly dependent on WNT/{beta}-catenin signaling and engineered endogenous WNT/{beta}-catenin signaling reporter organoids to biomark, isolate and characterize putative FT stem cells. Using functional approaches as well as bulk and single cell transcriptomic analyses, we show that an endogenous hormonally-regulated WNT7A-FZD5 signaling axis is critical for self-renewal of human FT stem cells, and that WNT/{beta}-catenin pathway-activated FT cells form a distinct transcriptomic cluster of cells enriched in ECM remodelling and integrin signaling pathways. In addition, we find that the WNT7A-FZD5 signaling axis is dispensable for mouse oviduct regeneration. Overall, we provide a deep characterization of FT stem cells and their molecular requirements for self-renewal, paving the way for mechanistic work investigating the role of stem cells in FT health and disease. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=165 SRC="FIGDIR/small/502319v3_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@124d8a0org.highwire.dtl.DTLVardef@9f92borg.highwire.dtl.DTLVardef@c57b33org.highwire.dtl.DTLVardef@11b5bec_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗