Transgenic neuromodulation tools have transformed the field of neuroscience over the past two decades by enabling targeted manipulation of neuronal populations and circuits with unprecedented specificity. Chemogenetic and optogenetic neuromodulation systems are among the most widely used and allow targeted control of neuronal activity through the administration of a selective compound or light, respectively. Innovative genetic targeting strategies are utilized to transduce specific cells to express transgenic receptors and opsins capable of manipulating neuronal activity. These allow mapping of neuroanatomical projection sites and link cellular manipulations with brain circuit functions and behavior. As these tools continue to expand knowledge of the nervous system in preclinical models, developing translational applications for human therapies is becoming increasingly possible. However, new strategies for implementing and monitoring transgenic tools are needed for safe and effective use in translational research and potential clinical applications. A major challenge for such applications is the need to track the location and function of chemogenetic receptors and opsins in vivo, and new developments in positron emission tomography (PET) imaging techniques offer promising solutions. The goal of this review is to summarize current research combining transgenic tools with PET for in vivo mapping and manipulation of brain circuits and to propose future directions for translational applications.
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http://dx.doi.org/10.1016/j.pbb.2021.173147 | DOI Listing |
Physiol Behav
December 2024
School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, PR China; The Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, The School of Life Science and Technology, Southeast University, 2 Sipailou Road, Nanjing, PR China. Electronic address:
Social isolation profoundly impacts motivated behavior and neural plasticity. While the effects of acute and chronic social isolation have been extensively studied, the consequences of intermittent isolation during adulthood, particularly relevant to modern lifestyles, remain poorly understood. This study investigated the impact of intermittent social isolation (ISI) on social behavior and brain activation in adult male mice.
View Article and Find Full Text PDFNeurobiol Learn Mem
December 2024
Department of Psychology, The University of Texas at Austin, Austin TX 78712, United States; Department of Neurology, The University of Texas at Austin, Austin TX 78712, United States; Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin TX 78712, United States. Electronic address:
The ability to choose between options that differ in their risks and rewards depends on brain regions within the mesocorticolimbic circuit and regulation of their activity by neurotransmitter systems. Dopamine neurotransmission in particular plays a critical role in modulating such risk-taking behavior; however, the contribution of other major modulatory neurotransmitters, such as acetylcholine, is not as well-defined, especially for decision making in which the risk associated with more rewarding outcomes involves adverse consequences. Consequently, the goal of the current experiments was to examine how cholinergic signaling influences decision making involving risk of explicit punishment.
View Article and Find Full Text PDFCurr Opin Neurobiol
December 2024
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Developmental Biology, Washington University School of Medicine, Saint Louis, MO 63110, USA; Brain Immunology and Glia Center, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address:
Critical periods are brief windows of heightened neural circuit plasticity that allow circuits to permanently reset their structure and function to facilitate robust organismal behavior. Understanding the cellular and molecular mechanisms that instruct critical period timing is of broad clinical interest, as altered developmental plasticity is linked to multiple neurodevelopmental disorders. While intrinsic, neuronal mechanisms shape both neural circuit remodeling and critical period timing, recent data indicate that signaling from astrocytes and surrounding glia can both promote and limit critical period plasticity.
View Article and Find Full Text PDFCell Rep
December 2024
Institute of Neuroscience, Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China; University of Chinese Academy of Sciences, Beijing 100049, China; Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 201210, China. Electronic address:
In the dorsal striatum (DS), the direct- and indirect-pathway striatal projection neurons (dSPNs and iSPNs) play crucial opposing roles in controlling actions. However, it remains unclear whether and how dSPNs and iSPNs provide distinct and specific contributions to decision-making, a process transforming sensory inputs to actions. Here, we perform causal interrogations on the roles of dSPNs and iSPNs in the posterior DS (pDS) in auditory-guided decision-making.
View Article and Find Full Text PDFCell Rep
December 2024
Center for Theoretical Neuroscience and Mortimer B Zuckerman Mind Brain Behavior Institute, Columbia University, New York City, NY 10027, USA; Department of Neuroscience, Swartz Program in Theoretical Neuroscience, Kavli Institute for Brain Science, College of Physicians and Surgeons and Mortimer B. Zuckerman Mind Brain Behavior Institute, Columbia University, New York City, NY 10027, USA.
Sensory systems use context to infer meaning. Accordingly, context profoundly influences neural responses to sensory stimuli. However, a cohesive understanding of the circuit mechanisms governing contextual effects across different stimulus conditions is still lacking.
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