Our brain has a language of its own. At the core of its complex functions is chemical communication occurring between and among neurons and astrocytes, which use an alphabet composed of a myriad secreted signaling molecules, including neurotransmitters, neuropeptides, hormones etc. Understanding the chemical language of the brain is a goal of fundamental importance, as many of these signaling molecules or the cellular receptors that relay their signals, are involved in diseases of the nervous system and are potential targets of pharmaceuticals that could restore physiological brain functions. Towards this goal, an important first step is to decipher the associations between animal behavior, neural activity, and the precise spatial and temporal dynamics of these secreted chemical neuromodulators.
To aid our understanding of neural communication, along with continuous improvements in neuroimaging technologies, a range of new molecular tools needs to be developed and deployed. Genetically encoded fluorescent sensors, such as the widely utilized calcium sensors GCaMPs, occupy the center stage, due to their ideal properties for in vivo imaging and their flexible combination with the most advanced imaging modalities.
Standing on the shoulders of these giants, recent developments by us and others led to the first genetically encoded indicators for dopamine (dLight1), a key neuromodulator best known for its roles in reward and motivation.
These ultrasensitive probes are built by engineering a single fluorescent protein (circularly permutated Green Fluorescent Protein) into G-protein coupled receptors (GPCRs).
Our team is interested in continuing the optimization and expansion of this neurotechnology toolbox, to shine a new light on the in vivo dynamics of diverse neuromodulatory molecules involved in neural communication. Our goal is to reveal previously hidden aspects of neural communication in intact living animals. Ultimately, the biological findings enabled by the new tools we propose to develop are expected to translate into new and improved therapeutic approaches for several neurological and neuropsychiatric disorders.
Within this context, we are pursuing the following overall objectives:
1) Development of novel high-quality sensors for chemical neuromodulators (i.e. monoamines, neuropeptides, neurohormones), optimized for in vitro and in vivo imaging with high sensitivity;
2) Deployment of these sensors in brain slices and awake behaving animals to investigate the spatial and temporal scales of neuromodulatory signals, as well as their relationship with neural circuit activity and animal behavior.
