TY - JOUR
T1 - Local accumbens in vivo imaging during deep brain stimulation reveals a strategy-dependent amelioration of hedonic feeding
AU - Wu, Hemmings
AU - Kakusa, Bina
AU - Neuner, Sophie
AU - Christoffel, Daniel J.
AU - Heifets, Boris D.
AU - Malenka, Robert C.
AU - Halpern, Casey H.
N1 - Funding Information:
ACKNOWLEDGMENTS. This study was supported by funds from K12NS080223 (to C.H.H.), K08MH110610 (to B.D.H.), and K99DK115985 (to D.J.C.), the Brain & Behavior Research Foundation (C.H.H. and D.J.C.), Neurosurgery Research and Education Foundation (C.H.H.), John A. Blume Foundation (C.H.H.), William Randolph Hearst Foundation (C.H.H.), and Stanford Medical Scholars Research Fellowship (C.H.H.), and start-up funds from Stanford’s Department of Neurosurgery (to C.H.H.).
Publisher Copyright:
© 2022 National Academy of Sciences. All rights reserved.
PY - 2022/1/4
Y1 - 2022/1/4
N2 - Impulsive overeating is a common, disabling feature of eating disorders. Both continuous deep brain stimulation (DBS) and responsive DBS, which limits current delivery to pathological brain states, have emerged as potential therapies. We used in vivo fiber photometry in wild-type, Drd1-cre, and A2a-cre mice to 1) assay subtype-specific medium spiny neuron (MSN) activity of the nucleus accumbens (NAc) during hedonic feeding of high-fat food, and 2) examine DBS strategy-specific effects on NAc activity. D1, but not D2, NAc GCaMP activity increased immediately prior to high-fat food approach. Responsive DBS triggered a GCaMP surge throughout the stimulation period and durably reduced high-fat intake. However, with continuous DBS, this surge decayed, and high-fat intake reemerged. Our results argue for a stimulation strategy-dependent modulation of D1 MSNs with a more sustained decrease in consumption with responsive DBS. This study illustrates the important role in vivo imaging can play in understanding effects of such novel therapies.
AB - Impulsive overeating is a common, disabling feature of eating disorders. Both continuous deep brain stimulation (DBS) and responsive DBS, which limits current delivery to pathological brain states, have emerged as potential therapies. We used in vivo fiber photometry in wild-type, Drd1-cre, and A2a-cre mice to 1) assay subtype-specific medium spiny neuron (MSN) activity of the nucleus accumbens (NAc) during hedonic feeding of high-fat food, and 2) examine DBS strategy-specific effects on NAc activity. D1, but not D2, NAc GCaMP activity increased immediately prior to high-fat food approach. Responsive DBS triggered a GCaMP surge throughout the stimulation period and durably reduced high-fat intake. However, with continuous DBS, this surge decayed, and high-fat intake reemerged. Our results argue for a stimulation strategy-dependent modulation of D1 MSNs with a more sustained decrease in consumption with responsive DBS. This study illustrates the important role in vivo imaging can play in understanding effects of such novel therapies.
KW - Deep brain stimulation
KW - Fiber photometry
KW - Hedonic feeding
KW - Nucleus accumbens
KW - Responsive neurostimulation
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U2 - 10.1073/pnas.2109269118
DO - 10.1073/pnas.2109269118
M3 - Article
C2 - 34921100
AN - SCOPUS:85122671594
SN - 0027-8424
VL - 119
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 1
M1 - e2109269118
ER -