Molecular-Level Functional Magnetic Resonance Imaging of Dopaminergic Signaling

Abstract

We demonstrate a technique for mapping brain activity that combines molecular specificity and spatial coverage using a neurotransmitter sensor detectable by magnetic resonance imaging (MRI). This molecular functional MRI (fMRI) method yielded time-resolved volumetric measurements of dopamine release evoked by reward-related lateral hypothalamic brain stimulation of rats injected with the neurotransmitter sensor. Peak dopamine concentrations and release rates were observed in the anterior nucleus accumbens core. Substantial dopamine transients were also present in more caudal areas. Dopamine-release amplitudes correlated with the rostrocaudal stimulation coordinate, suggesting participation of hypothalamic circuitry in modulating dopamine responses. This work provides a foundation for development and application of quantitative molecular fMRI techniques targeted toward numerous components of neural physiology.

Calcium-dependent molecular fMRI using a magnetic nanosensor

“…The magnitude of the average observed response was 13 ± 2%, comparable to the chemical stimulation paradigms of Figure 3, but here the response was evoked within seconds and peaked near the stimulus offset time (Figure 4c). This onset profile is similar to that reported previously using a closely-related stimulation paradigm in conjunction with a dopamine-sensitive MRI contrast agent 24 , reflecting the possibility that activation of MFB dopamine fibers contributes substantially to the observed calcium response.…”

“…Stimulation parameters chosen for the experiments were within range of previous studies 24,25 , and suitable for evoking robust self-stimulation behavior in a standard operant paradigm (Supplementary Figure S7), demonstrating their relevance to naturalistic behavior and its underlying neurophysiology. To measure calcium responses to the stimulation, MaCaReNas were infused into dorsal striatum and then imaged using a block design paradigm 26 in conjunction with T 2 -weighted spin echo echo planar imaging performed with a frame rate of 0.25 Hz, which is characteristic also of conventional hemodynamic fMRI.…”

Cross-hemispheric dopamine projections have functional significance

“…Dopamine transients have been studied extensively (1-13, 31-35); however, previous measurements were restricted to a single hemisphere, including those using a magnetic resonance imaging-compatible dopamine reporter (42), and few microdialysis experiments performed bilateral measurements (43). In the present work, we measured spontaneous dopamine efflux with millisecond time resolution in both hemispheres simultaneously and found synchronicity in release.…”

Flower-like gold nanostructures electrodeposited on indium tin oxide (ITO) glass as a SERS-active substrate for sensing dopamine

“…Thus, the sensitive and selective detection of abnormal dopamine level in biological fluid is very important in the early detection of several diseases such as schizophrenia, Huntington's and Parkinson's disease [1][2][3]. Common detection methods for neurotransmitters are based on electrochemistry [4][5][6][7][8], chromatography coupled to spectrometry [9][10][11][12][13], fluorescence [14][15][16] or surfaceenhanced Raman scattering [17][18][19][20][21].…”