Distinct neurochemical influences on fMRI response polarity in the striatum

Domenic H Cerri; Daniel L Albaugh; Lindsay R Walton; Brittany Katz; Tzu-Wen Wang; Tzu-Hao Harry Chao; Weiting Zhang; Randal J Nonneman; Jing Jiang; Sung-Ho Lee; Amit Etkin; Catherine N Hall; Garret D Stuber; Yen-Yu Ian Shih

doi:10.1038/s41467-024-46088-z

Distinct neurochemical influences on fMRI response polarity in the striatum

Nat Commun. 2024 Mar 1;15(1):1916. doi: 10.1038/s41467-024-46088-z.

Authors

Domenic H Cerri^#^{1

2

3}, Daniel L Albaugh^#^{1

2

3

4}, Lindsay R Walton^#^{1

2

3}, Brittany Katz^{1

2

3}, Tzu-Wen Wang^{1

2

3}, Tzu-Hao Harry Chao^{1

2

3}, Weiting Zhang^{1

2

3}, Randal J Nonneman^{1

2

3}, Jing Jiang^{5

6

7

8

9}, Sung-Ho Lee^{1

2

3}, Amit Etkin^{5

6

10}, Catherine N Hall^{11

12}, Garret D Stuber^{13

14

15}, Yen-Yu Ian Shih^{16

17

18}

Affiliations

¹ Center for Animal MRI, the University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
² Biomedical Research Imaging Center, the University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
³ Department of Neurology, the University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴ Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA, USA.
⁵ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
⁶ Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
⁷ Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
⁸ Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
⁹ Iowa Neuroscience Institute, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
¹⁰ Alto Neuroscience, Los Altos, CA, USA.
¹¹ Sussex Neuroscience, University of Sussex, Falmer, United Kingdom.
¹² School of Psychology, University of Sussex, Falmer, United Kingdom.
¹³ Center for Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, WA, USA.
¹⁴ Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.
¹⁵ Department of Pharmacology, University of Washington, Seattle, WA, USA.
¹⁶ Center for Animal MRI, the University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. shihy@unc.edu.
¹⁷ Biomedical Research Imaging Center, the University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. shihy@unc.edu.
¹⁸ Department of Neurology, the University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. shihy@unc.edu.

^# Contributed equally.

Abstract

The striatum, known as the input nucleus of the basal ganglia, is extensively studied for its diverse behavioral roles. However, the relationship between its neuronal and vascular activity, vital for interpreting functional magnetic resonance imaging (fMRI) signals, has not received comprehensive examination within the striatum. Here, we demonstrate that optogenetic stimulation of dorsal striatal neurons or their afferents from various cortical and subcortical regions induces negative striatal fMRI responses in rats, manifesting as vasoconstriction. These responses occur even with heightened striatal neuronal activity, confirmed by electrophysiology and fiber-photometry. In parallel, midbrain dopaminergic neuron optogenetic modulation, coupled with electrochemical measurements, establishes a link between striatal vasodilation and dopamine release. Intriguingly, in vivo intra-striatal pharmacological manipulations during optogenetic stimulation highlight a critical role of opioidergic signaling in generating striatal vasoconstriction. This observation is substantiated by detecting striatal vasoconstriction in brain slices after synthetic opioid application. In humans, manipulations aimed at increasing striatal neuronal activity likewise elicit negative striatal fMRI responses. Our results emphasize the necessity of considering vasoactive neurotransmission alongside neuronal activity when interpreting fMRI signal.

MeSH terms

Animals
Basal Ganglia
Corpus Striatum* / physiology
Dopaminergic Neurons
Humans
Magnetic Resonance Imaging* / methods
Neostriatum
Rats

Abstract

MeSH terms

Grants and funding