Noradrenergic Signaling Disengages Feedforward Transmission in the Nucleus Accumbens Shell

Manz, Kevin M.; Coleman, Benjamin C.; Grueter, Carrie A.; Shields, Brenda C.; Tadross, Michael R.; Grueter, Brad A.

doi:10.1523/jneurosci.2420-20.2021

Cited by 12 publications

(7 citation statements)

References 49 publications

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“…It seems, that the noradrenergic pathways innervating the striatal subfield, i.e. the NAcc shell, originating mainly from the A1 and A2 regions (Delfs et al 1998;Manz et al 2021), which could not be damaged by the unilateral administration of 6-OHDA into the left MFB, played a significant role in increasing the NA content in the ipsilateral STR. Thus, DES when administered in combination with L-DOPA could increase the level of NA, due to inhibition of its reuptake by NET at the terminals of the ascending noradrenergic pathways from regions A1 and A2, but it cannot be ruled out that L-DOPA itself could serve as a substrate for NA synthesis in these terminals, increasing the total NA pool in the ipsilateral STR.…”

Section: Impact Of Des and L-dopa On Motor Functionsmentioning

confidence: 99%

Behavioral and neurochemical interactions of the tricyclic antidepressant drug desipramine with L-DOPA in 6-OHDA-lesioned rats. Implications for motor and psychiatric functions in Parkinson’s disease

et al. 2022

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Rationale The pharmacological effects of antidepressants in modulating noradrenergic transmission as compared to serotonergic transmission in a rat model of Parkinson’s disease under chronic L-DOPA therapy are insufficiently explored. Objectives The aim of the present study was to investigate the effect of the tricyclic antidepressant desipramine administered chronically alone or jointly with L-DOPA, on motor behavior and monoamine metabolism in selected brain structures of rats with the unilateral 6-OHDA lesion. Methods The antiparkinsonian activities of L-DOPA and desipramine were assessed behaviorally using a rotation test and biochemically based on changes in the tissue concentrations of noradrenaline, dopamine and serotonin and their metabolites, evaluated separately for the ipsi- and contralateral motor (striatum, substantia nigra) and limbic (prefrontal cortex, hippocampus) structures of rat brain by HPLC method. Results Desipramine administered alone did not induce rotational behavior, but in combination with L-DOPA, it increased the number of contralateral rotations more strongly than L-DOPA alone. Both L-DOPA and desipramine + L-DOPA significantly increased DA levels in the ipsilateral striatum, substantia nigra, prefrontal cortex and the ipsi- and contralateral hippocampus. The combined treatment also significantly increased noradrenaline content in the ipsi- and contralateral striatum, while L-DOPA alone decreased serotonin level on both sides of the hippocampus. Conclusions The performed analysis of the level of monoamines and their metabolites in the selected brain structures suggests that co-modulation of noradrenergic and dopaminergic transmission in Parkinson’s disease by the combined therapy with desipramine + L-DOPA may have some positive implications for motor and psychiatric functions but further research is needed to exclude potential negative effects.

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Section: Impact Of Des and L-dopa On Motor Functionsmentioning

confidence: 99%

Behavioral and neurochemical interactions of the tricyclic antidepressant drug desipramine with L-DOPA in 6-OHDA-lesioned rats. Implications for motor and psychiatric functions in Parkinson’s disease

et al. 2022

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“…While norepinephrine’s role in sensory processing is understudied, recent work has begun to examine its role in reward-related tasks. In particular, recent evidence suggests that norepinephrine plays a role in modulating glutamatergic synapses in the nucleus accumbens, and that it might tune feedforward inhibition and impact reward-related circuitry as well as motivational states ( Manz et al, 2021 ). Animal studies have also suggested that norepinephrine is associated with the amount of effort required to perform a reward task (here, force exerted on a grip in order to receive a reward) and that this effort is distinct from reward sensitivity ( Varazzani et al, 2015 ; Borderies et al, 2020 ).…”

Section: Antidepressant Drugs and Predictive Processesmentioning

confidence: 99%

A Predictive Coding Framework for Understanding Major Depression

Gilbert

Wusinich

Zarate

2022

Front. Hum. Neurosci.

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Predictive coding models of brain processing propose that top-down cortical signals promote efficient neural signaling by carrying predictions about incoming sensory information. These “priors” serve to constrain bottom-up signal propagation where prediction errors are carried via feedforward mechanisms. Depression, traditionally viewed as a disorder characterized by negative cognitive biases, is associated with disrupted reward prediction error encoding and signaling. Accumulating evidence also suggests that depression is characterized by impaired local and long-range prediction signaling across multiple sensory domains. This review highlights the electrophysiological and neuroimaging evidence for disrupted predictive processing in depression. The discussion is framed around the manner in which disrupted generative predictions about the sensorium could lead to depressive symptomatology, including anhedonia and negative bias. In particular, the review focuses on studies of sensory deviance detection and reward processing, highlighting research evidence for both disrupted generative predictions and prediction error signaling in depression. The role of the monoaminergic and glutamatergic systems in predictive coding processes is also discussed. This review provides a novel framework for understanding depression using predictive coding principles and establishes a foundational roadmap for potential future research.

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“…PV tdT cells in the NAcc were visualized using Scientifica PatchVision software via 530 nm LED light. PV-FSIs were confirmed according to biophysical properties (capacitance, membrane resistance, and AMPAR decay kinetics) [11,17].…”

Section: Electrophysiologymentioning

confidence: 99%

“…For example, inhibition of NAc PV-FSIs increases impulsivity and decreases psychostimulant induced associative learning [14,15]. Studies from our lab and others indicate that feedforward glutamatergic synapses onto PV-FSIs exhibit multiple molecularly distinct modes of plasticity, each proceeding via Gprotein-coupled receptor (GPCR)-dependent mechanisms [10,11,16,17]. However, it is unknown whether endogenous opioid signaling, a neuromodulatory system critically involved in adaptive and pathological reward behavior, modulates PV-FSIembedded feedforward microcircuits.…”

Section: Introductionmentioning

confidence: 99%

“…Experience dependent plasticity of these inputs has been shown to underlie maladaptive motivational states [2][3][4][5][6][7]. NAcdependent motivational output is organized by networks of parvalbumin-expressing fast-spiking interneurons (PV-FSIs) that gate medium spiny neuron (MSN) output via feedforward inhibition [8][9][10][11][12][13]. For example, inhibition of NAc PV-FSIs increases impulsivity and decreases psychostimulant induced associative learning [14,15].…”

Section: Introductionmentioning

confidence: 99%

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Kappa opioid receptor modulation of excitatory drive onto nucleus accumbens fast-spiking interneurons

Coleman

Manz

Grueter

2021

Neuropsychopharmacol.

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The dynorphin/kappa opioid receptor (KOR) system within the nucleus accumbens (NAc) contributes to affective states. Parvalbumin fast-spiking interneurons (PV-FSIs), a key component of feedforward inhibition, participate in integration of excitatory inputs to the NAc by robustly inhibiting select populations of medium spiny output neurons, therefore greatly influencing NAc dependent behavior. How the dynorphin/KOR system regulates feedforward inhibition in the NAc remains unknown. Here, we elucidate the molecular mechanisms of KOR inhibition of excitatory transmission onto NAc PV-FSIs using a combination of wholecell patch-clamp electrophysiology, optogenetics, pharmacology, and a parvalbumin reporter mouse. We find that postsynaptic KOR stimulation induces long-term depression (LTD) of excitatory synapses onto PV-FSI by stimulating the endocytosis of AMPARs via a PKA and calcineurin-dependent mechanism. Furthermore, KOR regulation of PV-FSI synapses are input specific, inhibiting thalamic but not cortical inputs. Finally, following acute stress, a protocol known to elevate dynorphin/KOR signaling in the NAc, KOR agonists no longer inhibit excitatory transmission onto PV-FSI. In conclusion, we delineate pathway-specific mechanisms mediating KOR control of feedforward inhibitory circuits in the NAc and provide evidence for the recruitment of this system in response to stress.

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Noradrenergic Signaling Disengages Feedforward Transmission in the Nucleus Accumbens Shell

Cited by 12 publications

References 49 publications

Behavioral and neurochemical interactions of the tricyclic antidepressant drug desipramine with L-DOPA in 6-OHDA-lesioned rats. Implications for motor and psychiatric functions in Parkinson’s disease

Behavioral and neurochemical interactions of the tricyclic antidepressant drug desipramine with L-DOPA in 6-OHDA-lesioned rats. Implications for motor and psychiatric functions in Parkinson’s disease

A Predictive Coding Framework for Understanding Major Depression

Kappa opioid receptor modulation of excitatory drive onto nucleus accumbens fast-spiking interneurons

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