A novel approach to map induced activation of neuronal networks using chemogenetics and functional neuroimaging in rats: A proof-of-concept study on the mesocorticolimbic system

Roelofs, Theresia J. M.; Verharen, Jeroen P. H.; Tilborg, Geralda A. F. van; Boekhoudt, Linde; Toorn, Annette van der; Jong, Johannes de; Luijendijk, Mieneke C. M.; Otte, Willem M.; Adan, Roger A.H.; Dijkhuizen, Rick M.

doi:10.1016/j.neuroimage.2017.05.021

Cited by 45 publications

(62 citation statements)

References 39 publications

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“…DREADDs stimulation not only induced activation in the mesocorticolimbic regions but also drove BOLD response alterations at the whole‐brain level. In contrast to the altered neural activity, the functional connectivity remained stable after CNO injection (Roelofs et al, ). Although the authors reasoned that neural network activity and functional connectivity are not closely related, care must be taken when interpreting the lack of functional connectivity changes.…”

Section: Dreadds Combined With Imaging Techniquesmentioning

confidence: 99%

“…These local injections of the viral constructs allow spatial control of the DREADDs expression. Furthermore, the production of functional (Boender et al, 2014;Foldi, Milton, & Oldfield, 2017;Roelofs et al, 2017).…”

Section: Dreadds Development and Characterisationmentioning

confidence: 99%

“…CNO can be administered via different routes, including systemic injection (Alexander et al, 2009), intracerebral injection (Mahler et al, 2014), intracerebroventricular injection (Nakajima et al, 2016), in food or drinking water (Cassataro et al, 2014), or in eye drops (Keenan, Fernandez, Shumway, Zhao, & Hattar, 2017). Several studies found that the effects of CNO became apparent after 5-10 min, peaked after 45-50 min and lasted for at least 1-6 hr (Alexander et al, 2009;Roelofs et al, 2017;Vardy et al, 2015). Given this activation time course, the DREADD technology is usually preferred over optogenetics when neuronal activity must be sustainably manipulated over longer time periods.…”

Section: Dreadds Development and Characterisationmentioning

confidence: 99%

“…The CBF was significantly suppressed at the implantation site upon CNO administration, whereas the CBF remained constant in other brain areas . In a proof-of-concept study on the mesocorticolimbic system in rats, Roelofs et al expressed (Roelofs et al, 2017). Although the authors reasoned that neural network activity and functional connectivity are not closely related, care must be taken when interpreting the lack of functional connectivity changes.…”

Section: Dreadds Combined With Mrimentioning

confidence: 99%

“…Additionally, projection‐specific DREADDs expression can be obtained using Cre‐recombinase expressing canine adenovirus. This Cre‐recombinase expressing canine adenovirus is preferentially retrogradely transported to the neuronal somas, where it can interact with the Cre‐dependent DREADDs constructs to express the DREADDs (Boender et al, ; Foldi, Milton, & Oldfield, ; Roelofs et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Combining designer receptors exclusively activated by designer drugs and neuroimaging in experimental models: A powerful approach towards neurotheranostic applications

Peeters

Missault

Keliris

et al. 2020

British J Pharmacology

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The combination of chemogenetics targeting specific brain cell populations with in vivo imaging techniques provides scientists with a powerful new tool to study functional neural networks at the whole‐brain scale. A number of recent studies indicate the potential of this approach to increase our understanding of brain function in health and disease. In this review, we discuss the employment of a specific chemogenetic tool, designer receptors exclusively activated by designer drugs, in conjunction with non‐invasive neuroimaging techniques such as PET and MRI. We highlight the utility of using this multiscale approach in longitudinal studies and its ability to identify novel brain circuits relevant to behaviour that can be monitored in parallel. In addition, some identified shortcomings in this technique and more recent efforts to overcome them are also presented. Finally, we discuss the translational potential of designer receptors exclusively activated by designer drugs in neuroimaging and the promise it holds for future neurotheranostic applications.

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Section: Dreadds Combined With Imaging Techniquesmentioning

confidence: 99%

Section: Dreadds Development and Characterisationmentioning

confidence: 99%

Section: Dreadds Development and Characterisationmentioning

confidence: 99%

Section: Dreadds Combined With Mrimentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Combining designer receptors exclusively activated by designer drugs and neuroimaging in experimental models: A powerful approach towards neurotheranostic applications

Peeters

Missault

Keliris

et al. 2020

British J Pharmacology

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Memantine treatment does not affect compulsive behavior or frontostriatal connectivity in an adolescent rat model for quinpirole-induced compulsive checking behavior

et al. 2022

Self Cite

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Rationale Compulsivity often develops during childhood and is associated with elevated glutamate levels within the frontostriatal system. This suggests that anti-glutamatergic drugs, like memantine, may be an effective treatment. Objective Our goal was to characterize the acute and chronic effect of memantine treatment on compulsive behavior and frontostriatal network structure and function in an adolescent rat model of compulsivity. Methods Juvenile Sprague–Dawley rats received repeated quinpirole, resulting in compulsive checking behavior (n = 32; compulsive) or saline injections (n = 32; control). Eight compulsive and control rats received chronic memantine treatment, and eight compulsive and control rats received saline treatment for seven consecutive days between the 10th and 12th quinpirole/saline injection. Compulsive checking behavior was assessed, and structural and functional brain connectivity was measured with diffusion MRI and resting-state fMRI before and after treatment. The other rats received an acute single memantine (compulsive: n = 12; control: n = 12) or saline injection (compulsive: n = 4; control: n = 4) during pharmacological MRI after the 12th quinpirole/saline injection. An additional group of rats received a single memantine injection after a single quinpirole injection (n = 8). Results Memantine treatment did not affect compulsive checking nor frontostriatal structural and functional connectivity in the quinpirole-induced adolescent rat model. While memantine activated the frontal cortex in control rats, no significant activation responses were measured after single or repeated quinpirole injections. Conclusions The lack of a memantine treatment effect in quinpirole-induced compulsive adolescent rats may be partly explained by the interaction between glutamatergic and dopaminergic receptors in the brain, which can be evaluated with functional MRI.

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Multimodal methods to help interpret resting-state fMRI

Zhou

Jiang

Man

et al. 2023

Advances in Resting-State Functional MRI

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A novel approach to map induced activation of neuronal networks using chemogenetics and functional neuroimaging in rats: A proof-of-concept study on the mesocorticolimbic system

Cited by 45 publications

References 39 publications

Combining designer receptors exclusively activated by designer drugs and neuroimaging in experimental models: A powerful approach towards neurotheranostic applications

Combining designer receptors exclusively activated by designer drugs and neuroimaging in experimental models: A powerful approach towards neurotheranostic applications

Memantine treatment does not affect compulsive behavior or frontostriatal connectivity in an adolescent rat model for quinpirole-induced compulsive checking behavior

Multimodal methods to help interpret resting-state fMRI

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