Biology subjects

Guo, M. Y.

Publications and source records attributed to Guo, M. Y..

4 recordsLinked to original sources

bioRxiv2026

Local control of dopamine release in nucleus accumbens gates opioid withdrawal aversion

The opioid crisis has emphasized the need for more effective treatments for opioid use disorder (OUD)1-3, which is characterized by habitual opioid use to avoid withdrawal symptoms4,5. Both physical and affective symptoms contribute to opioid withdrawal yet whether different neural mechanisms mediate these different symptom domains and contribute distinctly to opioid relapse is unknown. While neurons expressing mu opioid receptors (MORs) gate opioids reinforcing effects6-8 by increasing dopamine (DA) release in nucleus accumbens (NAc), sharp decreases in NAc DA release are associated with withdrawal9-11, the cellular and circuit mechanisms of which are unknown. Here we describe an unusual population of evolutionarily-conserved MOR+ neurons in the NAc expressing the transcription factor Tshz1. Increased activity in these neurons is required for withdrawal aversion learning. Deletion of MORs in Tshz1 neurons prevented withdrawal-induced decreases in DA release and affective aversion, but not physical symptoms associated with withdrawal. Pharmacological activation of mGluR8, which is preferentially expressed in Tshz1 neurons, reduced withdrawal aversion. Thus, by dissociating the circuit mechanisms contributing to the physical and affective components of opioid withdrawal focusing on the critical role of Tshz1 neurons, we have identified a novel druggable target with therapeutic potential for treating key OUD withdrawal symptoms.

neuroscience↗

bioRxiv2025

Opponent regulation of striatal output pathways by dopamine and serotonin

Classic theories propose opponent functions for striatal dopamine (DA) and serotonin (5-hydroxytryptamine; 5HT), with DA promoting approach and 5HT promoting patience or avoidance. How these neuromodulators regulate downstream circuits to achieve such antagonistic effects remains mysterious. Here, we mapped striatal 5HT receptor expression and recorded from genetically-identified striatal neurons to demonstrate that DA and 5HT selectively activate distinct populations of striatal neurons to exert opponent control over striatal output.

neuroscience↗

bioRxiv2023

Striatal integration of inverse dopamine and serotonin signals gates learning

The neuromodulators dopamine (DA) and serotonin (5-hydroxytryptamine; 5HT) are powerful regulators of associative learning1-9. Similarities in the activity and connectivity of these neuromodulatory systems have inspired competing models of how DA and 5HT interact to drive the formation of new associations10-13. However, these hypotheses have yet to be tested directly because it has not been possible to precisely interrogate and manipulate multiple neuromodulatory systems in a single subject. Here, we establish a double transgenic mouse model enabling simultaneous genetic access to the brains DA and 5HT systems. Anterograde axon tracing revealed the nucleus accumbens (NAc) to be a putative hotspot for the integration of convergent DA and 5HT signals. Simultaneous recordings of DA and 5HT input activity in the NAc posterior medial shell revealed that DA axons are excited by rewards while 5HT axons are inhibited. Optogenetically blunting DA and 5HT reward responses simultaneously blocked learning about a reward-predictive cue. Optogenetically reproducing both DA and 5HT responses to reward, but not either one alone, was sufficient to drive the acquisition of new associations. Altogether, these results demonstrate that striatal integration of inverse DA and 5HT signals is a crucial mechanism gating associative learning.

neuroscience↗

bioRxiv2019

The Medicago truncatula HKT family: Ion transport properties and regulation of expression upon abiotic stresses and symbiosis

Soil salinity is one of the most important abiotic stresses affecting plant growth. In legumes, symbiotic nitrogen fixation in nodules is affected by salt stress, and salinity tolerance is variable among species. Genes from the High affinity K+ Transporter (HKT) family are known to play crucial roles in salt stress tolerance in different plant species. In legumes these transporters are still very poorly characterized.. Here we study the HKT transporter family from the model legume Medicago trunacatula, which is moderately tolerant to salinity. The genome of this species comprises five HKT genes, hereafter named MtHKT1;1 to MtHKT1;5. Phylogenetic analysis indicated that the MtHKT polypeptides belong to HKT subfamily 1. Three members (MtHKT1;2, MtHKT1;4 and MtHKT1;5) of the Medicago truncatula family were cloned and expressed in Xenopus oocytes. Their electrophysiological properties revealed a permeability 10 times higher for Na+ than for K+ and varying rectification properties. Expression analyses of the three MtHKT genes under different biotic and abiotic conditions suggested that MtHKT1;5 is the main transporter from this family in the root, the three genes sharing a decrease of expression in drought and salt stress conditions in non inoculated plants as well as plants inoculated with rhizobia. In the shoot, the three MtHKT would be present at similar levels independently on the applied stresses. Based on biomass and ion content analysis, the nodule appeared as the most sensitive organ to the applied salt and drought stresses. The level of expression of the three MtHKT genes was strongly decreased by both stresses in the nodule.

plant biology↗