Muscarinic Attenuation of Mnemonic Rule Representation in Macaque Dorsolateral Prefrontal Cortex during a Pro- and Anti-Saccade Task

Major, Alex James; Vijayraghavan, Susheel; Everling, Stefan

doi:10.1523/jneurosci.2454-15.2015

Cited by 33 publications

(46 citation statements)

References 95 publications

(11 reference statements)

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“…However, it is still possible that baseline ACh levels differ strongly between anesthetized and awake animals, and thus switches from facilitation to inhibition occur at different application levels. Despite this, the overwhelming number of studies reported that ACh application results on increased activity in V1 (Sillito and Kemp, 1983 ; Sillito et al, 1985 ; Sato et al, 1987 ; Roberts et al, 2005 ; Zinke et al, 2006 ; Herrero et al, 2008 ; Goard and Dan, 2009 ; Kuo et al, 2009 ; Rodriguez et al, 2010 ; Soma et al, 2012 , 2013 ; Pinto et al, 2013 ), and in other cortical areas (McKenna et al, 1988 ; Metherate et al, 1988a , b ; Matsumura et al, 1990 ; Tremblay et al, 1990 ; Bhattacharyya et al, 2012 , 2013 ; Thiele et al, 2012 ; Yang et al, 2013 ; Major et al, 2015 ; Sun et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Muscarinic and Nicotinic Contribution to Contrast Sensitivity of Macaque Area V1 Neurons

Herrero

Gieselmann

Thiele

2017

Front. Neural Circuits

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Acetylcholine is a neuromodulator that shapes information processing in different cortical and subcortical areas. Cell type and location specific cholinergic receptor distributions suggest that acetylcholine in macaque striate cortex should boost feed-forward driven activity, while also reducing population excitability by increasing inhibitory tone. Studies using cholinergic agonists in anesthetized primate V1 have yielded conflicting evidence for such a proposal. Here we investigated how muscarinic or nicotinic receptor blockade affect neuronal excitability and contrast response functions in awake macaque area V1. Muscarinic or nicotinic receptor blockade caused reduced activity for all contrasts tested, without affecting the contrast where neurons reach their half maximal response (c50). The activity reduction upon muscarinic and nicotinic blockade resulted in reduced neuronal contrast sensitivity, as assessed through neurometric functions. In the majority of cells receptor blockade was best described by a response gain model (a multiplicative scaling of responses), indicating that ACh is involved in signal enhancement, not saliency filtering in macaque V1.

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Section: Discussionmentioning

confidence: 99%

Muscarinic and Nicotinic Contribution to Contrast Sensitivity of Macaque Area V1 Neurons

Herrero

Gieselmann

Thiele

2017

Front. Neural Circuits

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“…Blocking dopamine receptor D1, for instance, revealed an "inverted U" dose-response relationship because too little or too much receptor activity reduces persistent firing (Vijayraghavan et al, 2007), and both D1 and D2 receptors influence the representation of task rules during a delay (Ott et al, 2014). Similarly, acetylcholine has been implicated in the maintenance of persistent activity through its action on nicotinic (Yang et al, 2013;Sun et al, 2017) and muscarinic receptors (Krnjevic et al, 1971;Andrade, 1991;Egorov et al, 2002), although a recent study demonstrated that the decrease in activity caused by muscarinic blockers is not specific to delay activity (Major et al, 2015), just as we observed for NMDARs. Furthermore, a2A-adrenoceptors (Li et al, 1999; also impact on persistent firing, in part by acting on nonselective cation-permeable transient receptor potential channels (TRP channels) (Yan et al, 2009) and hyperpolarization activated cyclic nucleotide-gated potassium channels (M. Wang et al, 2007;Thuault et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

The Contribution of AMPA and NMDA Receptors to Persistent Firing in the Dorsolateral Prefrontal Cortex in Working Memory

et al. 2020

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Many tasks demand that information is kept online for a few seconds before it is used to guide behavior. The information is kept in working memory as the persistent firing of neurons encoding the memorized information. The neural mechanisms responsible for persistent activity are not yet well understood. Theories attribute an important role to ionotropic glutamate receptors, and it has been suggested that NMDARs are particularly important for persistent firing because they exhibit long time constants. Ionotropic AMPARs have shorter time constants and have been suggested to play a smaller role in working memory. Here we compared the contribution of AMPARs and NMDARs to persistent firing in the dlPFC of male macaque monkeys performing a delayed saccade to a memorized spatial location. We used iontophoresis to eject small amounts of glutamate receptor antagonists, aiming to perturb, but not abolish, neuronal activity. We found that both AMPARs and NMDARs contributed to persistent activity. Blockers of the NMDARs decreased persistent firing associated with the memory of the neuron's preferred spatial location but had comparatively little effect on the representation of the antipreferred location. They therefore decreased the information conveyed by persistent firing about the memorized location. In contrast, AMPAR blockers decreased activity elicited by the memory of both the preferred and antipreferred location, with a smaller effect on the information conveyed by persistent activity. Our results provide new insights into the contribution of AMPARs and NMDARs to persistent activity during working memory tasks.

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“…Most of our understanding of the physiological consequences of PFC neuromodulation has been accrued from microiontophoretic, local and systemic injection studies in the PFC of monkeys performing the oculomotor delayed response task. Recently, several groups have begun to explore the role of dopamine in other PFC-dependent functions, including top-down attention (Noudoost and Moore, 2011a ; Soltani et al, 2013 ), visuomotor associative learning (Puig and Miller, 2012 ) and WM for abstract rules in numerical cognition and controlled oculomotor behavior (Jacob et al, 2013 ; Ott et al, 2014 ; Major et al, 2015 ; Vijayraghavan et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Neuromodulation of Prefrontal Cortex in Non-Human Primates by Dopaminergic Receptors during Rule-Guided Flexible Behavior and Cognitive Control

Vijayraghavan

Major

Everling

2017

Front. Neural Circuits

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The prefrontal cortex (PFC) is indispensable for several higher-order cognitive and executive capacities of primates, including representation of salient stimuli in working memory (WM), maintenance of cognitive task set, inhibition of inappropriate responses and rule-guided flexible behavior. PFC networks are subject to robust neuromodulation from ascending catecholaminergic systems. Disruption of these systems in PFC has been implicated in cognitive deficits associated with several neuropsychiatric disorders. Over the past four decades, a considerable body of work has examined the influence of dopamine on macaque PFC activity representing spatial WM. There has also been burgeoning interest in neuromodulation of PFC circuits involved in other cognitive functions of PFC, including representation of rules to guide flexible behavior. Here, we review recent neuropharmacological investigations conducted in our laboratory and others of the role of PFC dopamine receptors in regulating rule-guided behavior in non-human primates. Employing iontophoresis, we examined the effects of local manipulation of dopaminergic subtypes on neuronal activity during performance of rule-guided pro- and antisaccades, an experimental paradigm sensitive to PFC integrity, wherein deficits in performance are reliably observed in many neuropsychiatric disorders. We found dissociable effects of dopamine receptors on neuronal activity for rule representation and oculomotor responses and discuss these findings in the context of prior studies that have examined the role of dopamine in spatial delayed response tasks, attention, target selection, abstract rules, visuomotor learning and reward. The findings we describe here highlight the common features, as well as heterogeneity and context dependence of dopaminergic neuromodulation in regulating the efficacy of cognitive functions of PFC in health and disease.

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Muscarinic Attenuation of Mnemonic Rule Representation in Macaque Dorsolateral Prefrontal Cortex during a Pro- and Anti-Saccade Task

Cited by 33 publications

References 95 publications

Muscarinic and Nicotinic Contribution to Contrast Sensitivity of Macaque Area V1 Neurons

Muscarinic and Nicotinic Contribution to Contrast Sensitivity of Macaque Area V1 Neurons

The Contribution of AMPA and NMDA Receptors to Persistent Firing in the Dorsolateral Prefrontal Cortex in Working Memory

Neuromodulation of Prefrontal Cortex in Non-Human Primates by Dopaminergic Receptors during Rule-Guided Flexible Behavior and Cognitive Control

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