Norepinephrine Drives Persistent Activity in Prefrontal Cortex via Synergistic α1 and α2 Adrenoceptors

Zhang, Zizhen; Matos, Steven Cordeiro; Jego, Sonia; Adamantidis, Antoine; Séguéla, Philippe

doi:10.1371/journal.pone.0066122

Cited by 86 publications

(93 citation statements)

References 71 publications

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“…These data signify that the ␣ 1 -AR affects the striatum by delaying firing initiation and enhancing continued firing. Recently, it has been reported that noradrenaline drives persistent activity in rat prefrontal cortex via ␣ 1 -and ␣ 2 -ARs (Zhang et al, 2013). Although, at this moment, the precise roles of ␣ 1 -AR in the striatum are unknown, the enhancement of the late and post phase firing increment by phenylephrine is consistent with these reports.…”

Section: Slow Decay and Firing Incrementsupporting

confidence: 76%

Adrenergic receptor-mediated modulation of striatal firing patterns

Ohta

Kohno

Arake

et al. 2016

Neuroscience Research

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Although noradrenaline and adrenaline are some of the most important neurotransmitters in the central nervous system, the effects of noradrenergic/adrenergic modulation on the striatum have not been determined. In order to explore the effects of adrenergic receptor (AR) agonists on the striatal firing patterns, we used optogenetic methods which can induce continuous firings. We employed transgenic rats expressing channelrhodopsin-2 (ChR2) in neurons. The medium spiny neuron showed a slow rising depolarization during the 1-s long optogenetic striatal photostimulation and a residual potential with 8.6-s half-life decay after the photostimulation. As a result of the residual potential, five repetitive 1-sec long photostimulations with 20-s onset intervals cumulatively increased the number of spikes. This 'firing increment', possibly relating to the timing control function of the striatum, was used to evaluate the AR modulation. The β-AR agonist isoproterenol decreased the firing increment between the 1st and 5th stimulation cycles, while the α-AR agonist phenylephrine enhanced the firing increment. Isoproterenol and adrenaline increased the early phase (0-0.5s of the photostimulation) firing response. This adrenergic modulation was inhibited by the β-antagonist propranolol. Conversely, phenylephrine and noradrenaline reduced the early phase response. β-ARs and α-ARs work in opposition controlling the striatal firing initiation and the firing increment.

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Section: Slow Decay and Firing Incrementsupporting

confidence: 76%

Adrenergic receptor-mediated modulation of striatal firing patterns

Ohta

Kohno

Arake

et al. 2016

Neuroscience Research

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“…As mentioned in the Introduction, working memory is under tight control of catecholamine signaling in the PFC. In general, activation of D1Rs and α2ARs in the PFC facilitates working memory, while activation of α1ARs impairs these processes (Arnsten and Li, 2005, Arnsten, 2007, Hains and Arnsten, 2008, Zhang et al, 2013). Our finding that D1Rs and α1ARs reside together in PFC dendrites provides a potential neuroanatomical substrate for some opposing actions of these receptors.…”

Section: Discussionmentioning

confidence: 99%

D1-dopamine and α1-adrenergic receptors co-localize in dendrites of the rat prefrontal cortex

2014

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Functional interactions between dopaminergic and noradrenergic systems occur in many brain areas, including the prefrontal cortex (PFC). Biochemical, electrophysiological and behavioral data indicate crosstalk between D1 dopamine receptor (D1R) and α1-adrenergic receptor (α1AR) signaling in the PFC. However, it is unknown whether these interactions occur within the same neurons, or between neurons expressing either receptor. In this study, we used electron microscopy immunocytochemistry to demonstrate that D1Rs and α1ARs co-localize in rat PFC neuronal elements, most prominently in dendrites (60–70%), but also significantly in axon terminals, unmyelinated axons and spines (~20–30%). Our data also showed that the ratio of plasma membrane-bound to intracellular α1ARs is significantly reduced in D1R-expressing dendrites. Similar results were obtained using either a pan-α1AR or a selective α1bAR antibody to label noradrenergic receptors. Thus, these results demonstrate that D1Rs and α1ARs co-localize in PFC dendrites, thereby suggesting that the catecholaminergic effects on PFC function may be driven, at least in part, by cell-autonomous D1R-α1AR interactions.

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“…This long lasting depolarized state of neurons is evoked by stimulation of Gq-coupled receptors (mGluRs, muscarine Ach, 5-HT receptors) (Zhang et al, 2013) that results in the activation of the IP3 pathway and release of Ca ++ ions from the endoplasmic reticulum (Fowler et al, 2007). Elevation of the intracellular Ca ++ concentration activates the calcium-activated non selective cation current (iCAN) (Haj-Dahmane and Andrade, 1998), possibly mediated by the transient receptors potential channels (TRPCs) of both the prefrontal and entorhinal neurons (Fowler et al, 2007; Zhang et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Induction and modulation of persistent activity in a layer V PFC microcircuit model

Papoutsi

Sidiropoulou

Cutsuridis

et al. 2013

Front. Neural Circuits

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Working memory refers to the temporary storage of information and is strongly associated with the prefrontal cortex (PFC). Persistent activity of cortical neurons, namely the activity that persists beyond the stimulus presentation, is considered the cellular correlate of working memory. Although past studies suggested that this type of activity is characteristic of large scale networks, recent experimental evidence imply that small, tightly interconnected clusters of neurons in the cortex may support similar functionalities. However, very little is known about the biophysical mechanisms giving rise to persistent activity in small-sized microcircuits in the PFC. Here, we present a detailed biophysically—yet morphologically simplified—microcircuit model of layer V PFC neurons that incorporates connectivity constraints and is validated against a multitude of experimental data. We show that (a) a small-sized network can exhibit persistent activity under realistic stimulus conditions. (b) Its emergence depends strongly on the interplay of dADP, NMDA, and GABAB currents. (c) Although increases in stimulus duration increase the probability of persistent activity induction, variability in the stimulus firing frequency does not consistently influence it. (d) Modulation of ionic conductances (Ih, ID, IsAHP, IcaL, IcaN, IcaR) differentially controls persistent activity properties in a location dependent manner. These findings suggest that modulation of the microcircuit's firing characteristics is achieved primarily through changes in its intrinsic mechanism makeup, supporting the hypothesis of multiple bi-stable units in the PFC. Overall, the model generates a number of experimentally testable predictions that may lead to a better understanding of the biophysical mechanisms of persistent activity induction and modulation in the PFC.

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Norepinephrine Drives Persistent Activity in Prefrontal Cortex via Synergistic α1 and α2 Adrenoceptors

Cited by 86 publications

References 71 publications

Adrenergic receptor-mediated modulation of striatal firing patterns

Adrenergic receptor-mediated modulation of striatal firing patterns

D1-dopamine and α1-adrenergic receptors co-localize in dendrites of the rat prefrontal cortex

Induction and modulation of persistent activity in a layer V PFC microcircuit model

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