To this end, we designed a synthetic optical probe that can report extracellular catecholamine dynamics with high spatial and temporal fidelity within a unique near infrared (nIR) spectral profile.
To understand how neuromodulation sculpts brain activity, we sought to develop new tools that can optically report modulatory neurotransmitter concentrations in the brain extracellular space (ECS) in a manner that is compatible with pharmacology and other available tools to image neural structure and activity. However, the spatial limitations of fast-scan cyclic voltammetry (FSCV) and spatial and temporal limitations of microdialysis narrow our ability to interpret how neuromodulators affect the plasticity or function of individual neurons and synapses. The absence of direct change in ionic flux across cell membranes, which is measurable using available tools such as electrophysiology or genetically encoded voltage indicators, has necessitated the use of methods borrowed from analytical chemistry such as microdialysis and amperometry to study the dynamics of neuromodulation. Thus, modulatory neurotransmitter activity extends beyond single synaptic partners and enables small numbers of neurons to modulate the activity of broader networks ( 20). In contrast, neuromodulators (catecholamines and neuropeptides) may diffuse beyond the synaptic cleft and act via extrasynaptically expressed metabotropic receptors ( 14– 19). 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).
Modulatory neurotransmission is thought to occur on a broader spatial scale than classic neurotransmission, the latter of which is largely mediated by synaptic release of the amino acids glutamate (GLU) and γ-aminobutyric acid (GABA) in the central nervous system. DA, in particular, is thought to play a critical role in learning ( 6), motivation ( 7, 8), and motor control ( 9), and aberrations in DA neurotransmission are implicated in a wide range of neurological and psychiatric disorders including Parkinson’s disease ( 10), schizophrenia ( 11), and addiction ( 12).
The catecholamines dopamine (DA) and norepinephrine (NE) are neuromodulators known to play an important role in learning and attention and are implicated in multiple brain disorders ( 1– 5).
#NINOX SWIR 640 MOVIE#
A representative movie from optogenetic stimulation (five pulses at 25 Hz, 1 mW mm 2) in dorsal striatum. A representative movie from single-pulse electrical stimulation (0.3 mA) in dorsal striatum. Nomifensine extends nIRCat response to ChR2 stimulation of dopaminergic terminals in the dorsal striatum. Effect of quinpirole on ChR2 evoked nIRCat response at the level of ROIs.įig. Data that confirm targeting of optogenetic stimulation of dopaminergic and glutamatergic inputs to the striatum.įig. Variability in effect of quinpirole and sulpiride on nIRCat response on spatially segregated ROIs within a field of view.įig. Intensity of nIRCat labeling at baseline does not predict site of ∆ F/ F hotspots.įig. Brain slice nIRCat loading protocol and schematic of visible and nIR fluorescence microscopy for imaging nIRCats in brain tissue.įig. Surface-immobilized single nIRCats are reversible upon repeat exposure to DA.įig. nIRCats are compatible with concentrations and conditions expected in brain tissue.įig. Supplementary material for this article is available at įig.
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