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How neuromodulatory transmitters diffuse into the extracellular space remains an unsolved fundamental biological question, despite wide acceptance of the volume transmission model. Here, we report development of a method combining genetically encoded fluorescent sensors with high-resolution imaging and analysis algorithms which permits the first direct visualization of neuromodulatory transmitter diffusion at various neuronal and non-neuronal cells. Our analysis reveals that acetylcholine and monoamines diffuse at individual release sites with a spread length constant of ∼0.75 μm. These transmitters employ varied numbers of release sites, and when spatially close-packed release sites coactivate they can spillover into larger subcellular areas. Our data indicate spatially restricted (i.e., nonvolume) neuromodulatory transmission to be a prominent intercellular communication mode, reshaping current thinking of control and precision of neuromodulation crucial for understanding behaviors and diseases.

Depressive disorders are a common and debilitating form of mental illness with significant impacts on individuals and society. Despite the high prevalence, the underlying causes and mechanisms of depressive disorders are still poorly understood. Neurochemical systems, including serotonin, norepinephrine, and dopamine, have been implicated in the development and perpetuation of depressive symptoms. Current treatments for depression target these neuromodulator systems, but there is a need for a better understanding of their role in order to develop more effective treatments. Monitoring neurochemical dynamics during depressive symptoms is crucial for gaining a better a understanding of their involvement in depressive disorders. Genetically encoded sensors have emerged recently that offer high spatial–temporal resolution and the ability to monitor neurochemical dynamics in real time. This review explores the neurochemical systems involved in depression and discusses the applications and limitations of current monitoring tools for neurochemical dynamics. It also highlights the potential of genetically encoded sensors for better characterizing neurochemical dynamics in depression‐related behaviors. Furthermore, potential improvements to current sensors are discussed in order to meet the requirements of depression research. [ABSTRACT FROM AUTHOR]

In this issue of Cell Chemical Biology , Elleman et al. 1 introduce a transformative chemical approach to control neuronal activity with high spatial and temporal resolution. The authors present STX-bpc, a potent neurotoxin that naturally inhibits voltage-gated sodium channels (Na V s), complementing available optogenetic methods for manipulating neuronal activity, cellular communication, and behavior. In this issue of Cell Chemical Biology , Elleman et al.1 introduce a transformative chemical approach to control neuronal activity with high spatial and temporal resolution. The authors present STX-bpc, a potent neurotoxin that naturally inhibits voltage-gated sodium channels (Na V s), complementing available optogenetic methods for manipulating neuronal activity, cellular communication, and behavior. [ABSTRACT FROM AUTHOR]

Many neurodegenerative and neuropsychiatric diseases and other brain disorders are accompanied by impairments in high‐level cognitive functions including memory, attention, motivation, and decision‐making. Despite several decades of extensive research, neuroscience is little closer to discovering new treatments. Key impediments include the absence of validated and robust cognitive assessment tools for facilitating translation from animal models to humans. In this review, we describe a state‐of‐the‐art platform poised to overcome these impediments and improve the success of translational research, the Mouse Translational Research Accelerator Platform (MouseTRAP), which is centered on the touchscreen cognitive testing system for rodents. It integrates touchscreen‐based tests of high‐level cognitive assessment with state‐of‐the art neurotechnology to record and manipulate molecular and circuit level activity in vivo in animal models during human‐relevant cognitive performance. The platform also is integrated with two Open Science platforms designed to facilitate knowledge and data‐sharing practices within the rodent touchscreen community, touchscreencognition.org and mousebytes.ca. Touchscreencognition.org includes the Wall, showcasing touchscreen news and publications, the Forum, for community discussion, and Training, which includes courses, videos, SOPs, and symposia. To get started, interested researchers simply create user accounts. We describe the origins of the touchscreen testing system, the novel lines of research it has facilitated, and its increasingly widespread use in translational research, which is attributable in part to knowledge‐sharing efforts over the past decade. We then identify the unique features of MouseTRAP that stand to potentially revolutionize translational research, and describe new initiatives to partner with similar platforms such as McGill's M3 platform (m3platform.org). [ABSTRACT FROM AUTHOR]