The use of chemogenetic actuator ligands in nonhuman primate DREADDs-fMRI

Cushnie, Adriana K.; Bullock, Daniel; Manea, Ana M.G.; Tang, Wei; Zimmermann, Jan; Heilbronner, Sarah R.

doi:10.1016/j.crneur.2022.100072

Cited by 10 publications

(7 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Throughout this study, we used DCZ, a recently validated compound (Nagai et al, 2020) to activate the inhibitory DREADD receptors. This actuator is highly selective for DREADD receptors and enables precision targeting without concern for off-target effects on behavior or whole-brain functional connectivity (Upright and Baxter, 2020; Fujimoto et al, 2022; Cushnie et al, 2023). However, much of the initial and current research incorporating DREADDs uses clozapine-N-oxide (CNO; Armbruster et al, 2007; Grayson et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

“…To aid selective manipulation of DREADD-expressing cells and assess the causal influence of their projections across the brain, we used deschloroclozapine (DCZ). This actuating drug is proven to be inert and has no effect on whole-brain functional connectivity (Fujimoto et al, 2022; Cushnie et al, 2023) or on various types of behaviors (Nagai et al, 2020; Upright and Baxter, 2020; Mimura et al, 2021). DREADD-mediated inhibition of the amygdala increased the brain-wide rs-FC of this area, and specifically increased rs-FC between amygdala and frontal cortex.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation

Elorette,

Fujimoto,

Stoll

et al. 2023

Preprint

View full text Add to dashboard Cite

Measures of fMRI resting-state functional connectivity (rs-FC) are an essential tool for basic and clinical investigations of fronto-limbic circuits. Understanding the relationship between rs-FC and neural activity in these circuits is therefore vital. Here we introduced inhibitory designer receptors exclusively activated by designer drugs (DREADDs) into the macaque amygdala and activated them with a highly selective and potent DREADD agonist, deschloroclozapine. We evaluated the causal effect of activating the DREADD receptors on rs-FC and neural activity within circuits connecting amygdala and frontal cortex. Interestingly, activating the inhibitory DREADD increased rs-FC between amygdala and ventrolateral prefrontal cortex. Neurophysiological recordings revealed that the DREADD-induced increase in fMRI rs-FC was associated with increased local field potential coherency in the alpha band (6.5-14.5Hz) between amygdala and ventrolateral prefrontal cortex. Thus, our multi-disciplinary approach reveals the specific signature of neuronal activity that underlies rs-FC in fronto-limbic circuits.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation

Elorette,

Fujimoto,

Stoll

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…This might be a result of task-relevant cortical activity emerging, or remaining during the fixation period 21 . To estimate neural timescales at “rest”, work in anesthetized subjects or during sleep might be a viable alternative 9 , 38 , 39 , although these approaches come with their own disadvantages and confounds. We have previously shown that neural timescales estimated from fMRI data in anesthetized nonhuman primates replicated hierarchies derived from neuronal spiking data, although they did not perfectly match 9 .…”

Section: Discussionmentioning

confidence: 99%

Neural timescales reflect behavioral demands in freely moving rhesus macaques

Manea,

Maisson,

Voloh

et al. 2024

Nat Commun

Self Cite

View full text Add to dashboard Cite

Previous work demonstrated a highly reproducible cortical hierarchy of neural timescales at rest, with sensory areas displaying fast, and higher-order association areas displaying slower timescales. The question arises how such stable hierarchies give rise to adaptive behavior that requires flexible adjustment of temporal coding and integration demands. Potentially, this lack of variability in the hierarchical organization of neural timescales could reflect the structure of the laboratory contexts. We posit that unconstrained paradigms are ideal to test whether the dynamics of neural timescales reflect behavioral demands. Here we measured timescales of local field potential activity while male rhesus macaques foraged in an open space. We found a hierarchy of neural timescales that differs from previous work. Importantly, although the magnitude of neural timescales expanded with task engagement, the brain areas’ relative position in the hierarchy was stable. Next, we demonstrated that the change in neural timescales is dynamic and contains functionally-relevant information, differentiating between similar events in terms of motor demands and associated reward. Finally, we demonstrated that brain areas are differentially affected by these behavioral demands. These results demonstrate that while the space of neural timescales is anatomically constrained, the observed hierarchical organization and magnitude is dependent on behavioral demands.

show abstract

“…This might be a result of task-relevant cortical activity emerging or remaining during the fixation period. To estimate neural timescales at “rest”, work in anesthetized subjects or during sleep might be a viable alternative (for example, see Cushnie et al, 2023; Manea et al, 2022; Zilio et al, 2021), although these approaches come with their own disadvantages and confounds. We have previously shown that neural timescales estimated from fMRI data in anesthetized nonhuman primates replicated hierarchies derived from neuronal spiking data, although they did not perfectly match (Manea et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

Neural timescales reflect behavioral demands in freely moving rhesus macaques

Manea

Zilverstand

Hayden

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Previous work has demonstrated remarkably reproducible and consistent hierarchies of neural timescales across cortical areas at rest. The question arises how such stable hierarchies give rise to adaptive behavior that requires flexible adjustment of temporal coding and integration demands. Potentially, this previously found lack of variability in the hierarchical organization of neural timescales could be a reflection of the structure of the laboratory contexts in which they were measured. Indeed, computational work demonstrates the existence of multiple temporal hierarchies within the same anatomical network when the input structure is altered. We posit that unconstrained behavioral environments where relatively little temporal demands are imposed from the experimenter are an ideal test bed to address the question of whether the hierarchical organization and the magnitude of neural timescales reflect ongoing behavioral demands. To tackle this question, we measured timescales of local field potential activity while rhesus macaques were foraging freely in a large open space. We find a hierarchy of neural timescales that is unique to this foraging environment. Importantly, although the magnitude of neural timescales generally expanded with task engagement, the brain areas' relative position in the hierarchy was stable across the recording sessions. Notably, the magnitude of neural timescales monotonically expanded with task engagement across a relatively long temporal scale spanning the duration of the recording session. Over shorter temporal scales, the magnitude of neural timescales changed dynamically around foraging events. Moreover, the change in the magnitude of neural timescales contained functionally relevant information, differentiating between seemingly similar events in terms of motor demands and associated reward. That is, the patterns of change were associated with the cognitive and behavioral meaning of these events. Finally, we demonstrated that brain areas were differentially affected by these behavioral demands - i.e., the expansion of neural timescales was not the same across all areas. Together, these results demonstrate that the observed hierarchy of neural timescales is context-dependent and that changes in the magnitude of neural timescales are closely related to overall task engagement and behavioral demands.

show abstract

The use of chemogenetic actuator ligands in nonhuman primate DREADDs-fMRI

Cited by 10 publications

References 96 publications

The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation

The neural basis of resting-state fMRI functional connectivity in fronto-limbic circuits revealed by chemogenetic manipulation

Neural timescales reflect behavioral demands in freely moving rhesus macaques

Neural timescales reflect behavioral demands in freely moving rhesus macaques

Contact Info

Product

Resources

About