Optical imaging of prefrontal deficits induced by cocaine: neurons vs dopamine D2-receptor expressing neurons

Chelsea Pan; Kevin Clare

doi:10.1117/12.2544899

21 February 2020 Optical imaging of prefrontal deficits induced by cocaine: neurons vs dopamine D2-receptor expressing neurons

Chelsea Pan, Kevin Clare

Author Affiliations +

Proceedings Volume 11226, Neural Imaging and Sensing 2020; 112260V (2020) https://doi.org/10.1117/12.2544899
Event: SPIE BiOS, 2020, San Francisco, California, United States

Abstract

Deficits in the medial prefrontal cortex (mPFC) function play a crucial role in promoting compulsive cocaine use. This dysfunction might result from cocaine’s effects on neurons possibly including modification of the expression of the dopamine type 2 receptors (D2r). However, studies on D2r function have been hindered by relatively low receptor expression in mPFC and low detection sensitivity. To tackle this problem, we developed a workflow to optically image D2r through enhancing visualization of GFP fluorescence in a D2r-expressing transgenic mouse model. Two groups of animals were used: group 1 was treated daily by saline (0.1cc/100g, i.p.) and group 2 received cocaine (30mg/kg, i.p.) for 2 weeks. Following 1-day withdrawal, their brains were fixed and processed. The brain sections underwent immunostaining and ex vivo imaging using a confocal fluorescence microscope to capture co-registered fluorescence labeling of both neurons (NeuN) and D2r-expressing neurons (GFP). These images were montaged to cover a large field of view of the mPFC to quantify the changes in the count of neurons and D2r-expressing neurons. Our results show that chronic cocaine exposure results in 34.7%±5.7% decrease in neurons but a 44.7%±13.2% increase of D2r expressing neurons in the mPFC compared to saline treated group. Additionally, in-vivo Ca²⁺ imaging of D2r-expressing neurons in the mPFC revealed cocaine’s effects on the prefrontal response to the stimulation at the VTA. These changes might underlie the hypofrontality observed in human studies and exacerbate the loss of control associated with chronic cocaine use

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Chelsea Pan and Kevin Clare "Optical imaging of prefrontal deficits induced by cocaine: neurons vs dopamine D2-receptor expressing neurons", Proc. SPIE 11226, Neural Imaging and Sensing 2020, 112260V (21 February 2020); https://doi.org/10.1117/12.2544899

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