Differences in Noradrenaline Receptor Expression Across Different Neuronal Subtypes in Macaque Frontal Eye Field

Abstract

Cognitive functions such as attention and working memory are modulated by noradrenaline receptors in the prefrontal cortex (PFC). The frontal eye field (FEF) has been shown to play an important role in visual spatial attention. However, little is known about the underlying circuitry. The aim of this study was to characterize the expression of noradrenaline receptors on different pyramidal neuron and inhibitory interneuron subtypes in macaque FEF. Using immunofluorescence, we found broad expression of noradrenaline receptors across all layers of the FEF. Differences in the expression of different noradrenaline receptors were observed across different inhibitory interneuron subtypes. No significant differences were observed in the expression of noradrenaline receptors across different pyramidal neuron subtypes. However, we found that putative long-range projecting pyramidal neurons expressed all noradrenaline receptor subtypes at a much higher proportion than any of the other neuronal subtypes. Nearly all long-range projecting pyramidal neurons expressed all types of noradrenaline receptor, suggesting that there is no receptor-specific machinery acting on these long-range projecting pyramidal neurons. This pattern of expression among long-range projecting pyramidal neurons suggests a mechanism by which noradrenergic modulation of FEF activity influences attention and working memory.

Modulation of Spatial Memory Deficit and Hyperactivity in Dopamine Transporter Knockout Rats via α2A-Adrenoceptors

“…It directly stimulates postsynaptic α2A-adrenoceptor in the central nervous system and thereby enhances NE neurotransmission (47,48). The α2A-adrenoceptors are most densely represented in the PFC (30,49). Guanfacine acts directly on postsynaptic alpha-2A adrenoceptors in the PFC and has beneficial effects on regulating PFC functions (50,51).…”

Noradrenergic alpha-2a Receptor Stimulation Enhances Prediction Error Signaling in Anterior Cingulate Cortex and Striatum

“…Guanfacine’s behavioral effects might relate to overall firing rate changes in ACC or dlPFC based on studies indicating Guanfacine increases excitability in prefrontal pyramidal neurons (Wang et al, 2007; Barth et al, 2008; Kawaura et al, 2014). Since α2A adrenoceptors are likely differentially expressed in pyramidal neurons and interneurons (Kawaguchi and Shindou, 1998; Wang et al, 2013; Liu et al, 2014; Xing et al, 2016; Lee et al, 2020) we first split the neurons into narrow and broad spiking (NS and BS) neurons. Previous work has shown that fast spiking interneurons have faster (narrower) spike-width (Ardid et al, 2015; Oemisch et al, 2019), and that neurons with narrower spike-width suppress multiunit activity consistent with being inhibitory (Boroujeni et al, 2021).…”

Unilateral Oculomotor Nerve Palsy Associated With Primary Hypothyroidism: Two Case Reports

“…Both cases had significantly reduced levels of T3 at the presentation. One of the important functions of T3 is to enhance the response of β-adrenergic receptors [16]. We know that alpha and beta receptors are distributed both internally and externally in the eye.…”

“…The interaction between α2 and β1 receptors in the upper eyelid retractor muscle may be important in controlling the position of the upper eyelid and may explain the impairment of eyelid coaptation in hypothyroidism. Damage to certain elements of the sympathetic nervous system can inhibit this muscle and cause the phenomenon of eyelid ptosis, which has similarities to Horner's syndrome caused by sympathetic neuropathy [16,17].…”