Biology subjects

Elorette, C.

Publications and source records attributed to Elorette, C..

4 recordsLinked to original sources

bioRxiv2023

Pharmacological modulation of dopamine D1 and D2 receptors reveals distinct neural networks related to probabilistic learning in non-human primates.

The neurotransmitter dopamine (DA) has a multifaceted role in healthy and disordered brains through its action on multiple subtypes of dopaminergic receptors. How modulation of these receptors influences learning and motivation by altering intrinsic brain-wide networks remains unclear. Here we performed parallel behavioral and resting-state functional MRI experiments after administration of two different DA receptor antagonists in macaque monkeys. Systemic administration of SCH-23390 (D1 antagonist) slowed probabilistic learning when subjects had to learn new stimulus-reward associations and diminished functional connectivity (FC) in cortico-cortical and fronto-striatal connections. By contrast, haloperidol (D2 antagonist) improved learning and broadly enhanced FC in cortical connections. Further comparisons between the effect of SCH-23390/haloperidol on behavioral and resting-state FC revealed specific cortical and subcortical networks associated with the cognitive and motivational effects of DA manipulation, respectively. Thus, we reveal distinct brain-wide networks that are associated with the dopaminergic control of learning and motivation via DA receptors. Significance StatementD1 and D2 receptors are heavily implicated in cognitive and motivational processes, as well as in a number of psychiatric disorders. Despite this, little is known about how selective manipulation of these different receptors impacts cognition through changing activity across brain-wide intrinsic networks. Here, we examined the acute behavioral and brain-wide effects of D1 and D2 receptor-selective antagonists, SCH-23390 and haloperidol, in macaques performing a probabilistic learning task. SCH administration diminished, and haloperidol improved, animals task performance. Mirroring these effects on behavior, SCH reduced, and haloperidol increased, the resting-state functional connectivity across brain-wide networks, most notably in the cortico-striatal areas. Thus, our results highlight the opposing effects of D1 and D2 receptor modulation on the brain and behavior.

neuroscience↗

bioRxiv2023

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

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.

neuroscience↗

bioRxiv2023

High-throughput sequencing of macaque basolateral amygdala projections reveals dissociable connectional motifs with frontal cortex

The basolateral amygdala (BLA) projects widely across the macaque frontal cortex1-4, and amygdalo-frontal projections are critical for optimal emotional responding5 and decision- making6. Yet, little is known about the single-neuron architecture of these projections: namely, whether single BLA neurons project to multiple parts of the frontal cortex. Here, we use MAPseq7 to determine the projection patterns of over 3000 macaque BLA neurons. We found that one-third of BLA neurons have two or more distinct targets in parts of frontal cortex and of subcortical structures. Further, we reveal non-random structure within these branching patterns such that neurons with four targets are more frequently observed than those with two or three, indicative of widespread networks. Consequently, these multi-target single neurons form distinct networks within medial and ventral frontal cortex consistent with their known functions in regulating mood and decision-making. Additionally, we show that branching patterns of single neurons shape functional networks in the brain as assessed by fMRI-based functional connectivity. These results provide a neuroanatomical basis for the role of the BLA in coordinating brain-wide responses to valent stimuli8 and highlight the importance of high- resolution neuroanatomical data for understanding functional networks in the brain.

neuroscience↗

bioRxiv2021

Resting-state fMRI-based screening of deschloroclozapine in rhesus macaques predicts dosage-dependent behavioral effects

Chemogenetic techniques such as Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) enable transient, reversible, and minimally invasive manipulation of neural activity in vivo. Their development in non-human primates is essential for uncovering neural circuits contributing to cognitive functions and their translation to humans. One key issue that has delayed the development of chemogenetic techniques in primates is the lack of an accessible drug-screening method. Here, we utilize resting-state functional MRI (rs-fMRI), a non-invasive neuroimaging tool, to assess the impact of deschloroclozapine (DCZ) on brain-wide resting-state functional connectivity in seven rhesus macaques without DREADDs. We found that systemic administration of 0.1 mg/kg DCZ did not alter the resting-state functional connectivity. Conversely, 0.3 mg/kg of DCZ was associated with a prominent increase in functional connectivity that was mainly confined to the connections of frontal regions. Additional behavioral tests confirmed a negligible impact of 0.1 mg/kg DCZ on socio-emotional behaviors as well as on reaction time in a probabilistic learning task. 0.3 mg/kg DCZ did, however, slow responses in the probabilistic learning task, suggesting attentional or motivational deficits associated with hyperconnectivity in fronto-temporo-parietal networks. Our study highlights both the excellent selectivity of DCZ as a DREADD actuator, and the side-effects of its excess dosage. The results demonstrate the translational value of rs-fMRI as a drug-screening tool to accelerate the development of chemogenetics in primates.

neuroscience↗