Contribution of Ionotropic Glutamatergic Receptors to Excitability and Attentional Signals in Macaque Frontal Eye Field

Abstract Top-down attention, controlled by frontal cortical areas, is a key component of cognitive operations. How different neurotransmitters and neuromodulators flexibly change the cellular and network interactions with attention demands remains poorly understood. While acetylcholine and dopamine are critically involved, glutamatergic receptors have been proposed to play important roles. To understand their contribution to attentional signals, we investigated how ionotropic glutamatergic receptors in the frontal eye field (FEF) of male macaques contribute to neuronal excitability and attentional control signals in different cell types. Broad-spiking and narrow-spiking cells both required N-methyl-D-aspartic acid and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor activation for normal excitability, thereby affecting ongoing or stimulus-driven activity. However, attentional control signals were not dependent on either glutamatergic receptor type in broad- or narrow-spiking cells. A further subdivision of cell types into different functional types using cluster-analysis based on spike waveforms and spiking characteristics did not change the conclusions. This can be explained by a model where local blockade of specific ionotropic receptors is compensated by cell embedding in large-scale networks. It sets the glutamatergic system apart from the cholinergic system in FEF and demonstrates that a reduction in excitability is not sufficient to induce a reduction in attentional control signals.

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Cell class-specific modulation of attentional signals by acetylcholine in macaque frontal eye field

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1905413116 ◽

2019 ◽

Vol 116 (40) ◽

pp. 20180-20189 ◽

Cited By ~ 7

Author(s):

Miguel Dasilva ◽

Christian Brandt ◽

Sascha Gotthardt ◽

Marc Alwin Gieselmann ◽

Claudia Distler ◽

...

Keyword(s):

Attentional Control ◽

Nicotinic Receptors ◽

Neuronal Excitability ◽

Cell Types ◽

Frontal Eye Field ◽

Attentional Deficits ◽

Control Signals ◽

Eye Field ◽

High Level ◽

Muscarinic And Nicotinic Receptors

Attention is critical to high-level cognition, and attentional deficits are a hallmark of cognitive dysfunction. A key transmitter for attentional control is acetylcholine, but its cellular actions in attention-controlling areas remain poorly understood. Here we delineate how muscarinic and nicotinic receptors affect basic neuronal excitability and attentional control signals in different cell types in macaque frontal eye field. We found that broad spiking and narrow spiking cells both require muscarinic and nicotinic receptors for normal excitability, thereby affecting ongoing or stimulus-driven activity. Attentional control signals depended on muscarinic, not nicotinic receptors in broad spiking cells, while they depended on both muscarinic and nicotinic receptors in narrow spiking cells. Cluster analysis revealed that muscarinic and nicotinic effects on attentional control signals were highly selective even for different subclasses of narrow spiking cells and of broad spiking cells. These results demonstrate that cholinergic receptors are critical to establish attentional control signals in the frontal eye field in a cell type-specific manner.

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Illuminating the Neural Circuits Underlying Orienting of Attention

Vision ◽

10.3390/vision3010004 ◽

2019 ◽

Vol 3 (1) ◽

pp. 4 ◽

Cited By ~ 1

Author(s):

Michael Posner ◽

Cristopher Niell

Keyword(s):

Animal Models ◽

Superior Colliculus ◽

Large Scale ◽

Neural Circuits ◽

Cell Types ◽

Local Networks ◽

Sensory Stimuli ◽

Cortical Areas ◽

Large Scale Networks ◽

Human Neuroimaging

Human neuroimaging has revealed brain networks involving frontal and parietal cortical areas as well as subcortical areas, including the superior colliculus and pulvinar, which are involved in orienting to sensory stimuli. Because accumulating evidence points to similarities between both overt and covert orienting in humans and other animals, we propose that it is now feasible, using animal models, to move beyond these large-scale networks to address the local networks and cell types that mediate orienting of attention. In this opinion piece, we discuss optogenetic and related methods for testing the pathways involved, and obstacles to carrying out such tests in rodent and monkey populations.

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Oxytocin modulates the intrinsic dynamics between attention-related large scale networks

10.1101/371971 ◽

2018 ◽

Cited By ~ 1

Author(s):

Fei Xin ◽

Feng Zhou ◽

Xinqi Zhou ◽

Xiaole Ma ◽

Yayuan Geng ◽

...

Keyword(s):

Attentional Control ◽

Large Scale ◽

Functional Integration ◽

Network Dynamics ◽

Resting State Fmri ◽

Neural Systems ◽

Functional Dynamics ◽

Fmri Study ◽

N 93 ◽

Large Scale Networks

AbstractAttention and salience processing have been linked to the intrinsic between- and within-network dynamics of large scale networks engaged in internal (default mode network, DN) and external attention allocation (dorsal attention, DAN, salience network, SN). The central oxytocin (OXT) system appears ideally organized to modulate widely distributed neural systems and to regulate the switch between internal attention and salient stimuli in the environment. The current randomized placebo (PLC) controlled between-subject pharmacological resting-state fMRI study in N = 187 (OXT, n = 94; n = 93; single-dose intranasal administration) healthy male and female participants employed an independent component analysis (ICA) approach to determine the modulatory effects of OXT on the within- and between-network dynamics of the DAN-SN-DN triple network system. OXT increased the functional integration between subsystems within SN and DN and increased functional segregation of the DN with the SN and DAN engaged in attentional control. Whereas no sex differences were observed, OXT effects on the DN-SN interaction were modulated by autism traits. Together, the findings suggest that OXT may facilitate efficient attentional allocation towards social cues by modulating the intrinsic functional dynamics between DN components engaged in social processing and large-scale networks involved in external attentional demands (SN, DAN).

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Biophysical Support for Functionally Distinct Cell Types in the Frontal Eye Field

Journal of Neurophysiology ◽

10.1152/jn.90272.2008 ◽

2009 ◽

Vol 101 (2) ◽

pp. 912-916 ◽

Cited By ~ 23

Author(s):

Jeremiah Y. Cohen ◽

Pierre Pouget ◽

Richard P. Heitz ◽

Geoffrey F. Woodman ◽

Jeffrey D. Schall

Keyword(s):

Action Potentials ◽

Cell Types ◽

Frontal Eye Field ◽

Subcortical Structures ◽

Brain Areas ◽

Visual Neurons ◽

Distinct Cell ◽

Eye Field ◽

And Function ◽

Different Cell Types

Numerous studies have described different functional cell types in the frontal eye field (FEF), but the reliability of the distinction between these types has been uncertain. Studies in other brain areas have described specific differences in the width of action potentials recorded from different cell types. To substantiate the functionally defined cell types encountered in FEF, we measured the width of spikes of visual, movement, and visuomovement types of FEF neurons in macaque monkeys. We show that visuomovement neurons had the thinnest spikes, consistent with a role in local processing. Movement neurons had the widest spikes, consistent with their role in sending eye movement commands to subcortical structures such as the superior colliculus. Visual neurons had wider spikes than visuomovement neurons, consistent with their role in receiving projections from occipital and parietal cortex. These results show how structure and function of FEF can be linked to guide inferences about neuronal architecture.

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Corrigendum: Frontal eye field, where art thou? Anatomy, function, and non-invasive manipulation of frontal regions involved in eye movements and associated cognitive operations

Frontiers in Integrative Neuroscience ◽

10.3389/fnint.2014.00088 ◽

2014 ◽

Vol 8 ◽

Cited By ~ 2

Author(s):

Marine Vernet ◽

Romain Quentin ◽

Lorena Chanes ◽

Andres Mitsumasu ◽

Antoni Valero-Cabre

Keyword(s):

Eye Movements ◽

Frontal Eye Field ◽

Non Invasive ◽

Cognitive Operations ◽

Eye Field

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Frontal eye field, where art thou? Anatomy, function, and non-invasive manipulation of frontal regions involved in eye movements and associated cognitive operations

Frontiers in Integrative Neuroscience ◽

10.3389/fnint.2014.00066 ◽

2014 ◽

Vol 8 ◽

Cited By ~ 28

Author(s):

Marine Vernet ◽

Romain Quentin ◽

Lorena Chanes ◽

Andres Mitsumasu ◽

Antoni Valero-CabrÃ©

Keyword(s):

Eye Movements ◽

Frontal Eye Field ◽

Non Invasive ◽

Cognitive Operations ◽

Eye Field

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Intracellular Properties of Deep-Layer Pyramidal Neurons in Frontal Eye Field of Macaque Monkeys

Frontiers in Synaptic Neuroscience ◽

10.3389/fnsyn.2021.725880 ◽

2021 ◽

Vol 13 ◽

Author(s):

Charlotte Piette ◽

Marie Vandecasteele ◽

Clémentine Bosch-Bouju ◽

Valérie Goubard ◽

Vincent Paillé ◽

...

Keyword(s):

Pyramidal Neurons ◽

Deep Layer ◽

Brain Slices ◽

Cell Types ◽

Frontal Eye Field ◽

Visual Responses ◽

Biophysical Properties ◽

Eye Field

Although many details remain unknown, several positive statements can be made about the laminar distribution of primate frontal eye field (FEF) neurons with different physiological properties. Most certainly, pyramidal neurons in the deep layer of FEF that project to the brainstem carry movement and fixation signals but clear evidence also support that at least some deep-layer pyramidal neurons projecting to the superior colliculus carry visual responses. Thus, deep-layer neurons in FEF are functionally heterogeneous. Despite the useful functional distinctions between neuronal responses in vivo, the underlying existence of distinct cell types remain uncertain, mostly due to methodological limitations of extracellular recordings in awake behaving primates. To substantiate the functionally defined cell types encountered in the deep layer of FEF, we measured the biophysical properties of pyramidal neurons recorded intracellularly in brain slices issued from macaque monkey biopsies. Here, we found that biophysical properties recorded in vitro permit us to distinguish two main subtypes of regular-spiking neurons, with, respectively, low-resistance and low excitability vs. high-resistance and strong excitability. These results provide useful constraints for cognitive models of visual attention and saccade production by indicating that at least two distinct populations of deep-layer neurons exist.

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Composition and Topographic Organization of Signals Sent From the Frontal Eye Field to the Superior Colliculus

Journal of Neurophysiology ◽

10.1152/jn.2000.83.4.1979 ◽

2000 ◽

Vol 83 (4) ◽

pp. 1979-2001 ◽

Cited By ~ 214

Author(s):

Marc A. Sommer ◽

Robert H. Wurtz

Keyword(s):

Superior Colliculus ◽

Visual Analysis ◽

Sampling Bias ◽

Frontal Eye Field ◽

Visual Responses ◽

Topographic Organization ◽

Specific Subset ◽

Cognitive Operations ◽

Eye Field ◽

Movement Field

The frontal eye field (FEF) and superior colliculus (SC) contribute to saccadic eye movement generation, and much of the FEF's oculomotor influence may be mediated through the SC. The present study examined the composition and topographic organization of signals flowing from FEF to SC by recording from FEF neurons that were antidromically activated from rostral or caudal SC. The first and most general result was that, in a sample of 88 corticotectal neurons, the types of signals relayed from FEF to SC were highly diverse, reflecting the general population of signals within FEF rather than any specific subset of signals. Second, many neurons projecting from FEF to SC carried signals thought to reflect cognitive operations, namely tonic discharges during the delay period of a delayed-saccade task (delay signals), elevated discharges during the gap period of a gap task (gap increase signals), or both. Third, FEF neurons discharging during fixation were found to project to the SC, although they did not project preferentially to rostral SC, where similar fixation neurons are found. Neurons that did project preferentially to the rostral SC were those with foveal visual responses and those pausing during the gap period of the gap task. Many of the latter neurons also had foveal visual responses, presaccadic pauses in activity, and postsaccadic increases in activity. These two types of rostral-projecting neurons therefore may contribute to the activity of rostral SC fixation neurons. Fourth, conduction velocity was used as an indicator of cell size to correct for sampling bias. The outcome of this correction procedure suggested that among the most prevalent neurons in the FEF corticotectal population are those carrying putative cognitive-related signals, i.e., delay and gap increase signals, and among the least prevalent are those carrying presaccadic burst discharges but lacking peripheral visual responses. Fifth, corticotectal neurons carrying various signals were biased topographically across the FEF. Neurons with peripheral visual responses but lacking presaccadic burst discharges were biased laterally, neurons with presaccadic burst discharges but lacking peripheral visual responses were biased medially, and neurons carrying delay or gap increase signals were biased dorsally. Finally, corticotectal neurons were distributed within the FEF as a function of their visual or movement field eccentricity and projected to the SC such that eccentricity maps in both structures were closely aligned. We conclude that the FEF most likely influences the activity of SC neurons continuously from the start of fixation, through visual analysis and cognitive manipulations, until a saccade is generated and fixation begins anew. Furthermore, the projection from FEF to SC is highly topographically organized in terms of function at both its source and its termination.

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