Here we design and optimize a genetically encoded fluorescent indicator, iAChSnFR, for the ubiquitous neurotransmitter acetylcholine, based on a bacterial periplasmic binding protein. iAChSnFR shows large fluorescence changes, rapid rise and decay kinetics, and insensitivity to most cholinergic drugs. iAChSnFR revealed large transients in a variety of slice andin vivopreparations in mouse, fish, fly and worm. iAChSnFR will be useful for the study of acetylcholine in all animals.

Serotonin (5-HT) is a phylogenetically conserved monoamine neurotransmitter modulating a variety of processes in the brain. To directly visualize the dynamics of 5-HT, we developed a genetically encoded G PC R - A ctivation- B ased 5-HT (GRAB _5-HT ) sensor with high sensitivity, selectivity, and spatiotemporal resolution. GRAB _5-HT , detected 5-HT release in multiple physiological and pathological conditions in both flies and mice, and thus provides new insights into the dynamics and mechanisms of 5-HT signaling.

Serotonin-mediated intercellular communication has been implicated in myriad human behaviors and diseases, yet how serotonin communicates and how the communication is regulated remain unclear due to limitations of available monitoring tools. Here, we report a method multiplexing genetically encoded sensor-based imaging and fast-scan cyclic voltammetry, enabling simultaneous recordings of synaptic, perisynaptic, proximate and distal extrasynaptic serotonergic transmission. Employing this method alongside a genetically encoded sensor-based image analysis program (GESIAP), we discovered that heterogeneous firing patterns of serotonergic neurons create various transmission modes in the mouse raphe nucleus and amygdala, encoding information of firing pulse frequency, number, and synchrony using neurotransmitter quantity, releasing synapse count, and synaptic and/or volume transmission. During tonic and low-frequency phasic activities, serotonin is confined within synaptic clefts due to efficient retrieval by perisynaptic transporters, mediating synaptic transmission modes. Conversely, during high-frequency, especially synchronized phasic activities, or when transporter inhibition, serotonin may surpass transporter capacity, and escape synaptic clefts through 1‒3 outlet channels, leading to volume transmission modes. Our results elucidate a mechanism of how channeled synaptic enclosures, synaptic properties, and transporters collaborate to define the coding principles of activity pattern-dependent serotonergic transmission modes.

Fouling exists in almost every circulating cooling water system. It greatly harms to the operation of the system. According to their formation, fouling can be classified into crystallization fouling, particulate fouling, chemical reaction fouling, corrosion fouling, biological fouling, condensation fouling and mixed fouling. There are many factors influence fouling, and the main factors include the fluid temperature, flow rate, heat-transfer surface temperature and so on. The formation of fouling involves origin, transport, adhesion, exfoliation and aging stage. Due to difference of the formation mechanism and applicable conditions, fouling models are also different. Two typical models were introduced in the paper.