Dopamine Modulation of Prefrontal Cortex Activity Is Manifold and Operates at Multiple Temporal and Spatial Scales

Lohani, Sweyta; Martig, Adria K.; Deisseroth, Karl; Witten, Ilana B.; Moghaddam, Bita

doi:10.1016/j.celrep.2019.03.012

Cited by 68 publications

(49 citation statements)

References 85 publications

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“…It is estimated that one DA neuron provides input to several thousand neurons in the striatum and vice-versa, any given individual striatal neuron is influenced by DA released from more than one hundred DA projections. The DA neuronal system is often described in terms of DA release (tonic or phasic) and several models have tried to explain how multiple functions can be effectively impacted by different temporal DA release patterns ( Eshel et al., 2015 ; Berke, 2018 ; Lohani et al., 2019 ; Mohebi et al., 2019 ). DA neurons are intrinsic pacemakers, with a slow (2–4 Hz) rhythmic activity associated with a tonic feed-forward control on DA receptor activation.…”

Section: Section 1: Dopamine Receptorsmentioning

confidence: 99%

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Martel¹,

McArthur²

2020

Front. Pharmacol.

170

125

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Dopamine receptors are widely distributed within the brain where they play critical modulator roles on motor functions, motivation and drive, as well as cognition. The identification of five genes coding for different dopamine receptor subtypes, pharmacologically grouped as D1- (D1 and D5) or D2-like (D2S, D2L, D3, and D4) has allowed the demonstration of differential receptor function in specific neurocircuits. Recent observation on dopamine receptor signaling point at dopamine—glutamate-NMDA neurobiology as the most relevant in schizophrenia and for the development of new therapies. Progress in the chemistry of D1- and D2-like receptor ligands (agonists, antagonists, and partial agonists) has provided more selective compounds possibly able to target the dopamine receptors homo and heterodimers and address different schizophrenia symptoms. Moreover, an extensive evaluation of the functional effect of these agents on dopamine receptor coupling and intracellular signaling highlights important differences that could also result in highly differentiated clinical pharmacology. The review summarizes the recent advances in the field, addressing the relevance of emerging new targets in schizophrenia in particular in relation to the dopamine – glutamate NMDA systems interactions.

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Section: Section 1: Dopamine Receptorsmentioning

confidence: 99%

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Martel¹,

McArthur²

2020

Front. Pharmacol.

170

125

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“…In vivo, dopaminergic inputs from VTA was shown to modulate firing patterns and local field potential (LFP) oscillatory activity in PFC. [30] Activation of dopamine receptor-D1 positive PFC neurons also activates its burst firing, as indicated by higher firing rate and lower inter-spike intervals (ISIs). [31] To examine whether our hMO-hFO could recapitulate key in vivo electrophysiological features, we recorded and analyzed the spontaneous firing in hFOs and acoustically-fused hFO-hMO assembloids by calcium imaging.…”

Section: )[22]mentioning

confidence: 99%

Controllable Fusion of Human Brain Organoids Using Acoustofluidics

Cai

et al. 2020

Preprint

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The fusion of human organoids holds promising potential in modeling physiological and pathological processes of tissue genesis and organogenesis. However, current fused organoid models face challenges of high heterogeneity and variable reproducibility, which may stem from the random fusion of heterogeneous organoids. Thus, we developed a simple and versatile acoustofluidic method to improve the standardization of fused organoid models via a controllable spatial arrangement of organoids. By regulating dynamic acoustic fields within a hexagonal acoustofluidic device, we can rotate, transport, and fuse one organoid with another in a contact-free, label-free, and minimal-impact manner. As a proof-of-concept to model ventral tegmentum (VTA)-prefrontal cortex (PFC) projection, we acoustically fused human forebrain organoids (hFOs) and human midbrain organoids (hMOs) with the controllable alignment of neuroepithelial buds. We characterized the successful development of fused assembloids via robust tyrosine hydroxylase (TH) neuron projection, accompanied by an increase of firing rates and synchrony of excitatory neurons. Moreover, we found that our controllable fusion can promote neuron projection (e.g., range, length, and density), projection maturation (e.g., higher firing rate and synchrony), and neural progenitor cell (NPC) division in the assembloids. Thus, our acoustofluidic method would facilitate the standardization and robustness of organoid-based disease models and tissue engineering.

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“…Moreover, results of a recent electrochemical study [39] show that optically induced dopamine release in the nucleus accumbens continued to rise as the pulse frequency was increased from 40-50 pulses s −1 . Poor frequency-following fidelity was found by Lohani and colleagues in midbrain dopamine neurons optically stimulated at 100 pulses s −1 [40], suggesting that the upper limit on the induced firing rate lies at a significantly lower pulse frequency.…”

Section: Supporting Informationmentioning

confidence: 99%

“…The form and parameters of this function for eICSS of the MFB were described by Solomon et al [14]. In the absence of analogous data for oICSS, we have assumed the same functional form but have tuned the parameters to accommodate the power-frequency trade-off data reported here and results of prior studies [37–40].…”

Section: Supporting Informationmentioning

confidence: 99%

“…In contrast, midbrain dopamine neurons are directly activated substrate in the current study. Not only do these neurons have more limited frequency-following abilities than their MFB counterparts [38, 40], their activation is due to optical excitation of a relatively slow opsin [36] rather than to electrical excitation of voltage-sensitive membrane channels. As we show below, it is likely that the highest pulse frequencies employed in the present study did not always succeed in driving reward intensity to its maximum, particularly in the vehicle condition.…”

Section: Supporting Informationmentioning

confidence: 99%

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The effect of dopamine transporter blockade on optical self-stimulation: behavioral and computational evidence for parallel processing in brain reward circuitry

Trujillo-Pisanty

Conover

Solis

et al. 2019

Preprint

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The neurobiological study of reward was launched by the discovery of intracranial self-stimulation (ICSS). Subsequent investigation of this phenomenon provided the initial link between reward-seeking behavior and dopaminergic neurotransmission. We re-evaluated this relationship by psychophysical, pharmacological, optogenetic, and computational means. In rats working for direct, optical activation of midbrain dopamine neurons, we varied the strength and opportunity cost of the stimulation and measured time allocation, the proportion of trial time devoted to reward pursuit. We found that the dependence of time allocation on the strength and cost of stimulation was similar formally to that observed when electrical stimulation of the medial forebrain bundle served as the reward. When the stimulation is strong and cheap, the rats devote almost all their time to reward pursuit; time allocation falls off as stimulation strength is decreased and/or its opportunity cost is increased. A 3D plot of time allocation versus stimulation strength and cost produces a surface resembling the corner of a plateau (the “reward mountain”). We show that dopamine-transporter blockade shifts the mountain along both the strength and cost axes in rats working for optical activation of midbrain dopamine neurons. In contrast, the same drug shifted the mountain uniquely along the opportunity-cost axis when rats worked for electrical MFB stimulation in a prior study. Dopamine neurons are an obligatory stage in the dominant model of ICSS, which positions them at a key nexus in the final common path for reward seeking. This model fails to provide a cogent account for the differential effect of dopamine transporter blockade on the reward mountain. Instead, we propose that midbrain dopamine neurons and neurons with non-dopaminergic, MFB axons constitute parallel limbs of brain-reward circuitry that ultimately converge on the final-common path for the evaluation and pursuit of rewards. Author summary To succeed in the struggle for survival and reproductive success, animals must make wise choices about which goals to pursue and how much to pay to attain them. How does the brain make such decisions and adjust behaviour accordingly? An animal model that has long served to address this question entails delivery of rewarding brain stimulation. When the probe is positioned appropriately in the brain, rats will work indefatigably to trigger such stimulation. Dopamine neurons play a crucial role in this phenomenon. The dominant model of the brain circuitry responsible for the reward-seeking behavior treats these cells as a gateway through which the reward-generating brain signals must pass. Here, we challenge this idea on the basis of an experiment in which the dopamine neurons were activated selectively and directly. Mathematical modeling of the results argues for a new view of the structure of brain reward circuitry. On this view, the pathway(s) in which the dopamine neurons are embedded is one of a set of parallel channels that process reward s...

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Dopamine Modulation of Prefrontal Cortex Activity Is Manifold and Operates at Multiple Temporal and Spatial Scales

Cited by 68 publications

References 85 publications

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Dopamine Receptor Subtypes, Physiology and Pharmacology: New Ligands and Concepts in Schizophrenia

Controllable Fusion of Human Brain Organoids Using Acoustofluidics

The effect of dopamine transporter blockade on optical self-stimulation: behavioral and computational evidence for parallel processing in brain reward circuitry

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