Dopamine D1 and D2 Receptors Make Dissociable Contributions to Dorsolateral Prefrontal Cortical Regulation of Rule-Guided Oculomotor Behavior

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

doi:10.1016/j.celrep.2016.06.031

Cited by 29 publications

(54 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Past studies have reported that drug-induced modulation of discharge characteristics, signal-to-noise ratio, and coding of task attributes can be different between cortical neuronal classes (Mountcastle et al, 1969;Jacob et al, 2013;Ma et al, 2015;Thiele et al, 2016). To ascertain whether cholinergic stimulation had differential effects on putative pyramidal neurons and interneurons defined by electrophysiological characteristics, we performed a similar analysis, whereby we classified prefrontal neurons (n ϭ 68; see Materials and Methods) as broad-spiking (putative pyramidal neurons) or narrow-spiking (putative nonpyramidal neurons; see Materials and Methods;Johnston et al, 2009).…”

Section: Effects Of Carbachol On Putative Pyramidal and Nonpyramidal mentioning

confidence: 99%

“…However, we cannot discount nicotinic involvement in carbachol's actions reported here. Although nicotinic receptor stimulation can augment working memory activity in PFC (Yang et al, 2013;Sun et al, 2017) and can improve cognitive performance (Terry et al, 2015), other studies have shown that low doses of nicotinic antagonist enhanced attentional performance in rodents (Hahn et al, 2011) and improved delayed match-to-sample performance in monkeys (Terry et al, 1999). In the physiological context, Yang et al (2013) showed that low-dose iontophoretic stimulation of ␣7 nicotinic receptors during oculomotor delayed responses increased macaque DLPFC neuronal excitability and improved memory period spatial tuning, whereas ␣7 receptor antagonist reduced delay period activity and spatial tuning.…”

Section: Effects Of Carbachol On Task Selectivity Of Dlpfc Neuronsmentioning

confidence: 99%

“…In addition, advancements in the design of cholinergic agonists allow researchers to dissociate the actions of specific receptor subtypes (Bubser et al, 2012;Ferreira-Vieira et al, 2016). Although cholinergic stimulation has shown some promise in improving cognitive performance in macaques (Buccafusco and Terry, 2004;Tsukada et al, 2004) and Alzheimer's disease patients (Bodick et al, 1997), its influence on local PFC neurophysiology has been less examined in primates (Inoue et al, 1983;Sawaguchi and Matsumura, 1985).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Cholinergic Overstimulation Attenuates Rule Selectivity in Macaque Prefrontal Cortex

Major¹,

Vijayraghavan

Everling

2017

J. Neurosci.

Self Cite

View full text Add to dashboard Cite

Acetylcholine is released in the prefrontal cortex (PFC) and is a key modulator of cognitive performance in primates. Cholinergic stimulation has been shown to have beneficial effects on performance of cognitive tasks, and cholinergic receptors are being actively explored as promising targets for ameliorating cognitive deficits in Alzheimer's disease. We hypothesized that cholinergic stimulation of PFC during performance of a cognitive task would augment neuronal activity and neuronal coding of task attributes. We iontophoretically applied the general cholinergic receptor agonist carbachol onto neurons in dorsolateral PFC (DLPFC) of male rhesus macaques performing rule-guided prosaccades and antisaccades, a well established oculomotor task for testing cognitive control. Carbachol application had heterogeneous effects on neuronal excitability, with both excitation and suppression observed in significant proportions. Contrary to our prediction, neurons with rule-selective activity exhibited a reduction in selectivity during carbachol application. Cholinergic stimulation disrupted rule selectivity regardless of whether it had suppressive or excitatory effects on these neurons. In addition, cholinergic stimulation excited putative pyramidal neurons, whereas the activity of putative interneurons remained unchanged. Moreover, cholinergic stimulation attenuated saccade direction selectivity in putative pyramidal neurons due to nonspecific increases in activity. Our results suggest excessive cholinergic stimulation has detrimental effects on DLPFC representations of task attributes. These findings delineate the complexity and heterogeneity of neuromodulation of cerebral cortex by cholinergic stimulation, an area of active exploration with respect to the development of cognitive enhancers. The neurotransmitter acetylcholine is known to be important for cognitive processes in the prefrontal cortex. Removal of acetylcholine from prefrontal cortex can disrupt short-term memory performance and is reminiscent of Alzheimer's disease, which is characterized by degeneration of acetylcholine-producing neurons. Stimulation of cholinergic receptors is being explored to create cognitive enhancers for the treatment of Alzheimer's disease and other psychiatric diseases. Here, we stimulated cholinergic receptors in prefrontal cortex and examined its effects on neurons that are engaged in cognitive behavior. Surprisingly, cholinergic stimulation decreased neurons' ability to discriminate between rules. This work suggests that overstimulation of acetylcholine receptors could disrupt neuronal processing during cognition and is relevant to the design of cognitive enhancers based on stimulating the cholinergic system.

show abstract

Section: Effects Of Carbachol On Putative Pyramidal and Nonpyramidal mentioning

confidence: 99%

Section: Effects Of Carbachol On Task Selectivity Of Dlpfc Neuronsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cholinergic Overstimulation Attenuates Rule Selectivity in Macaque Prefrontal Cortex

Major¹,

Vijayraghavan

Everling

2017

J. Neurosci.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Experimental and modelling studies of dopamine on persistent activity in working memory have focused on isolated local brain regions, generally in the lateral prefrontal cortex (Brunel and Wang 2001;Durstewitz et al 2000;Jacob et al 2016;Vijayraghavan et al 2016Vijayraghavan et al , 2007Wang et al 2019;Williams and Goldman-Rakic 1995), where it has been shown that dopamine can enhance persistent activity through its effects on the NMDA and GABA receptors (Seamans et al 2001a,b;Seamans and Yang 2004;Wang et al 2013). If the effects of dopamine are truly restricted to small areas of cortex, then dopamine seems unlikely to be able to engage the widespread distributed activity seen during active working memory.…”

Section: Introductionmentioning

confidence: 99%

A dopamine gradient controls access to distributed working memory in monkey cortex

Bliss

Ding

Jankovic-Rapan

et al. 2020

Preprint

View full text Add to dashboard Cite

SummaryDopamine is critical for working memory. However, its effects throughout the large-scale primate cortex are poorly understood. Here we report that dopamine receptor density per neuron, measured by receptor autoradiography in the macaque monkey cortex, displays a macroscopic gradient along the cortical hierarchy. We developed a connectome- and biophysically-based model for distributed working memory that incorporates multiple neuron types and a dopamine gradient. The model captures an inverted U-shaped dependence of working memory on dopamine. The spatial distribution of mnemonic persistent activity matches that observed in over 90 experimental studies. We show that dopamine filters out irrelevant stimuli by enhancing inhibition of pyramidal cell dendrites. The level of cortical dopamine can also determine whether memory encoding is through persistent activity or an internal synaptic state. Taken together, our work represents a cross-level understanding that links molecules, cell types, recurrent circuit dynamics and a core cognitive function distributed across the cortex.

show abstract

“…We refer to this paradigm as the asynchronous cue (AC) design. This version of the task is often used in primate experiments as well (e.g., Amador et al, 1998;Johnston et al, 2014;Koval et al, 2014;Vijayraghavan et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Inhibition failures and late errors in the antisaccade task: influence of cue delay

Aponte

Tschan

Stephan

et al. 2018

Journal of Neurophysiology

View full text Add to dashboard Cite

In the antisaccade task participants are required to saccade in the opposite direction of a peripheral visual cue (PVC). This paradigm is often used to investigate inhibition of reflexive responses as well as voluntary response generation. However, it is not clear to what extent different versions of this task probe the same underlying processes. Here, we explored with the Stochastic Early Reaction, Inhibition, and late Action (SERIA) model how the delay between task cue and PVC affects reaction time (RT) and error rate (ER) when pro- and antisaccade trials are randomly interleaved. Specifically, we contrasted a condition in which the task cue is presented prior to the PVC with a condition in which the PVC serves also as task cue. Summary statistics indicate that ER and RTs are reduced and contextual effects largely removed when the task is signaled before the PVC appears. The SERIA model accounts for RT and ER in both conditions, and better so than other candidate models. Modeling demonstrates that voluntary pro- and antisaccades are frequent in both conditions. Moreover, early task cue presentation results in better control of reflexive saccades leading to fewer fast antisaccade errors and more rapid correct prosaccades. Finally, high latency errors are shown to be prevalent in both conditions. In summary, SERIA provides an explanation for the differences in the delayed and non-delayed antisaccade task.

show abstract

Dopamine D1 and D2 Receptors Make Dissociable Contributions to Dorsolateral Prefrontal Cortical Regulation of Rule-Guided Oculomotor Behavior

Cited by 29 publications

References 50 publications

Cholinergic Overstimulation Attenuates Rule Selectivity in Macaque Prefrontal Cortex

Cholinergic Overstimulation Attenuates Rule Selectivity in Macaque Prefrontal Cortex

A dopamine gradient controls access to distributed working memory in monkey cortex

Inhibition failures and late errors in the antisaccade task: influence of cue delay

Contact Info

Product

Resources

About