Imaging Striatal Dopamine Release Using a Non-Genetically Encoded Near-Infrared Fluorescent Catecholamine Nanosensor

Abraham G. Beyene; Kristen Delevich; Jackson Travis Del Bonis-O’Donnell; David J. Piekarski; Wan Chen Lin; A. Wren Thomas; Sarah J. Yang; Polina Kosillo; Darwin Yang; Linda Wilbrecht; Markita P. Landry

The catecholamines dopamine and norepinephrine are neuromodulators known to play an important role in learning and attention and are implicated in multiple brain disorders. [1] [2] [3] [4] [5] Dopamine, in particular, is thought to play a critical role in learning 6 , motivation 7, 8 , and motor control 9 , and aberrations in dopamine neurotransmission are implicated in a wide range of neurological and psychiatric disorders including Parkinson's disease 10 , schizophrenia 11 , and addiction. 12 Neuromodulatory neurotransmission is thought to occur on a broader spatial scale than classic neurotransmission, which is largely mediated by synaptic release of the amino acids glutamate and γ-aminobutyric acid (GABA) in the central nervous system. In synaptic glutamatergic and GABAergic neurotransmission, neurotransmitter concentrations briefly rise in the synaptic cleft to mediate local communication between the pre-and postsynaptic neurons through the rapid activation of ligand-gated ion channels. 13 In contrast, neuromodulators (catecholamines, neuropeptides) may diffuse beyond the synaptic cleft and act via extrasynaptically-expressed metabotropic receptors. [14] [15] [16] [17] [18] [19] Thus, modulatory neurotransmitter activity extends beyond single synaptic partners and enables small numbers of neurons to modulate the activity of broader networks. 20 The absence of direct change in ionic flux across cell membranes, which is measurable using available tools like electrophysiology or genetically encoded voltage indicators (GEVIs), has necessitated the use of methods borrowed from analytical chemistry such as microdialysis and amperometry to study the dynamics of neuromodulation. However, spatial limitations of fast-scan cyclic voltammetry and spatial and temporal limitations of microdialysis currently make it difficult to interpret how neuromodulators affect the plasticity or function of target neural populations at behaviorally relevant spatiotemporal scales.