Serotonergic Suppression of Mouse Prefrontal Circuits Implicated in Task Attention

Tian, Michael K.; Schmidt, Eric F.; Lambe, Evelyn K.

doi:10.1523/eneuro.0269-16.2016

Cited by 18 publications

(23 citation statements)

References 110 publications

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“…We have reported that the inactivation of excitatory neurons in the medial PFC inhibits the formation and retrieval of cocaine-associated memories [54]. An application of 5-HT inhibits pyramidal neurons through the activation of several types of 5-HT receptors including 5-HT 1A [55]. Anatomically, DRN 5-HT neurons strongly innervate the PFC [23].…”

Section: Discussionmentioning

confidence: 99%

The Role of Dorsal Raphe Serotonin Neurons in the Balance between Reward and Aversion

Nagai

Takayama

Nishitani

et al. 2020

IJMS

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Background: Reward processing is fundamental for animals to survive and reproduce. Many studies have shown the importance of dorsal raphe nucleus (DRN) serotonin (5-HT) neurons in this process, but the strongly correlative link between the activity of DRN 5-HT neurons and rewarding/aversive potency is under debate. Our primary objective was to reveal this link using two different strategies to transduce DRN 5-HT neurons. Methods: For transduction of 5-HT neurons in wildtype mice, adeno-associated virus (AAV) bearing the mouse tryptophan hydroxylase 2 (TPH2) gene promoter was used. For transduction in Tph2-tTA transgenic mice, AAVs bearing the tTA-dependent TetO enhancer were used. To manipulate the activity of 5-HT neurons, optogenetic actuators (CheRiff, eArchT) were expressed by AAVs. For measurement of rewarding/aversive potency, we performed a nose-poke self-stimulation test and conditioned place preference (CPP) test. Results: We found that stimulation of DRN 5-HT neurons and their projections to the ventral tegmental area (VTA) increased the number of nose-pokes in self-stimulation test and CPP scores in both targeting methods. Concomitantly, CPP scores were decreased by inhibition of DRN 5-HT neurons and their projections to VTA. Conclusion: Our findings indicate that the activity of DRN 5-HT neurons projecting to the VTA is a key modulator of balance between reward and aversion.

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Section: Discussionmentioning

confidence: 99%

The Role of Dorsal Raphe Serotonin Neurons in the Balance between Reward and Aversion

Nagai

Takayama

Nishitani

et al. 2020

IJMS

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“…Exploitation would be governed by low tonic 5-HT in mPFC and orbitofrontal cortex, whereas exploration would be induced when 5-HT levels are high in either area. Potential cellular mechanisms for this effect have been described by Tian et al. (2016) .…”

Section: Main Textmentioning

confidence: 99%

Neuromodulation of Attention

Thiele

Bellgrove

2018

Neuron

300

298

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Attention is critical to high-level cognition and attention deficits are a hallmark of neurologic and neuropsychiatric disorders. Although years of research indicates that distinct neuromodulators influence attentional control, a mechanistic account that traverses levels of analysis (cells, circuits, behavior) is missing. However, such an account is critical to guide the development of next-generation pharmacotherapies aimed at forestalling or remediating the global burden associated with disorders of attention. Here, we summarize current neuroscientific understanding of how attention affects single neurons and networks of neurons. We then review key results that have informed our understanding of how neuromodulation shapes these neuron and network properties and thereby enables the appropriate allocation of attention to relevant external or internal events. Finally, we highlight areas where we believe hypotheses can be formulated and tackled experimentally in the near future, thereby critically increasing our mechanistic understanding of how attention is implemented at the cellular and network levels.

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“…The deepest layer of prefrontal cortex, layer 6, is emerging as a key player in attentional control (Zikopoulos and Barbas, 2006 ; Béhuret et al, 2015 ; Wimmer et al, 2015 ). This layer sends extensive projections to thalamic nuclei (Mercer et al, 2005 ; Watts and Thomson, 2005 ; West et al, 2006 ; Zikopoulos and Barbas, 2006 ; Thomson, 2010 ) and to local circuit interneurons in cerebral cortex (Olsen et al, 2012 ; Tian et al, 2016 ). The corticothalamic connections are critical for top-down control of attentional processes (Miller and Cohen, 2001 ; Alitto and Usrey, 2003 ; Sherman, 2007 ; Wallace and Bertrand, 2013 ) and the corticocortical connections mediate cortical gain control (Olsen et al, 2012 ; Kim et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Opposing Cholinergic and Serotonergic Modulation of Layer 6 in Prefrontal Cortex

Sparks

Tian

Sargin

et al. 2018

Front. Neural Circuits

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Prefrontal cortex is a hub for attention processing and receives abundant innervation from cholinergic and serotonergic afferents. A growing body of evidence suggests that acetylcholine (ACh) and serotonin (5-HT) have opposing influences on tasks requiring attention, but the underlying neurophysiology of their opposition is unclear. One candidate target population is medial prefrontal layer 6 pyramidal neurons, which provide feedback modulation of the thalamus, as well as feed-forward excitation of cortical interneurons. Here, we assess the response of these neurons to ACh and 5-HT using whole cell recordings in acute brain slices from mouse cortex. With application of exogenous agonists, we show that individual layer 6 pyramidal neurons are bidirectionally-modulated, with ACh and 5-HT exerting opposite effects on excitability across a number of concentrations. Next, we tested the responses of layer 6 pyramidal neurons to optogenetic release of endogenous ACh or 5-HT. These experiments were performed in brain slices from transgenic mice expressing channelrhodopsin in either ChAT-expressing cholinergic neurons or Pet1-expressing serotonergic neurons. Light-evoked endogenous neuromodulation recapitulated the effects of exogenous neurotransmitters, showing opposing modulation of layer 6 pyramidal neurons by ACh and 5-HT. Lastly, the addition of 5-HT to either endogenous or exogenous ACh significantly suppressed the excitation of pyramidal neurons in prefrontal layer 6. Taken together, this work suggests that the major corticothalamic layer of prefrontal cortex is a substrate for opposing modulatory influences on neuronal activity that could have implications for regulation of attention.

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Serotonergic Suppression of Mouse Prefrontal Circuits Implicated in Task Attention

Abstract: Visual Abstract

Cited by 18 publications

References 110 publications

The Role of Dorsal Raphe Serotonin Neurons in the Balance between Reward and Aversion

The Role of Dorsal Raphe Serotonin Neurons in the Balance between Reward and Aversion

Neuromodulation of Attention

Opposing Cholinergic and Serotonergic Modulation of Layer 6 in Prefrontal Cortex

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