Dopamine Receptor Expression Among Local and Visual Cortex-Projecting Frontal Eye Field Neurons

Abstract

Dopaminergic modulation of prefrontal cortex plays an important role in numerous cognitive processes, including attention. The frontal eye field (FEF) is modulated by dopamine and has an established role in visual attention, yet the underlying circuitry upon which dopamine acts is not known. We compared the expression of D1 and D2 dopamine receptors (D1Rs and D2Rs) across different classes of FEF neurons, including those projecting to dorsal or ventral extrastriate cortex. First, we found that both D1Rs and D2Rs are more prevalent on pyramidal neurons than on several classes of interneurons and are particularly prevalent on putatively long-range projecting pyramidals. Second, higher proportions of pyramidal neurons express D1Rs than D2Rs. Third, overall a higher proportion of inhibitory neurons expresses D2Rs than D1Rs. Fourth, among inhibitory interneurons, a significantly higher proportion of parvalbumin+ neurons expresses D2Rs than D1Rs, and a significantly higher proportion of calbindin+ neurons expresses D1Rs than D2Rs. Finally, compared with D2Rs, virtually all of the neurons with identified projections to both dorsal and ventral extrastriate visual cortex expressed D1Rs. Our results demonstrate that dopamine tends to act directly on the output of the FEF and that dopaminergic modulation of top-down projections to visual cortex is achieved predominately via D1Rs.

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

“…We studied the pattern of adrenergic receptor expression across different layers and different classes of neurons in the FEF. Since evidence points to coexpression and cooperativity of dopamine receptors and adrenergic receptors in the PFC (Montezinho et al, 2006;Mitrano et al, 2014), we hypothesize that α1 and β1 adrenergic receptors might be expressed more heavily on long-range projecting pyramidal neurons, whereas α2 and β2 adrenergic receptors might be expressed more heavily on GABAergic interneurons, similar to patterns of dopamine expression in the FEF that have been found in previous studies (Mueller et al, 2018(Mueller et al, , 2020.…”

“…than either neurogranin+ or RP+ general pyramidal neuron classes across all four adrenergic receptor subtypes. The disproportionately high rate of adrenergic receptor expression among long-range projecting pyramidal neurons mirrors what was found for dopamine receptors in macaque FEF (Mueller et al, 2018(Mueller et al, , 2020. However, unlike dopamine receptors, which had higher rates of expression of D1Rs compared to D2Rs (Mueller et al, 2020), all four adrenergic receptor subtypes are expressed in very similar proportions on longrange pyramidal neurons.…”

“…The disproportionately high rate of adrenergic receptor expression among long-range projecting pyramidal neurons mirrors what was found for dopamine receptors in macaque FEF (Mueller et al, 2018(Mueller et al, , 2020. However, unlike dopamine receptors, which had higher rates of expression of D1Rs compared to D2Rs (Mueller et al, 2020), all four adrenergic receptor subtypes are expressed in very similar proportions on longrange pyramidal neurons. Although dopamine has been shown to modulate the influence of FEF neurons on visual signals (Noudoost and Moore, 2011a;Mueller et al, 2020), the role of noradrenaline is much less-understood.…”

“…In fact, in spite of the wealth of evidence demonstrating FEF neurons contribute significantly to fundamental components of cognition, no previous work has examined the laminar and cell-type distribution of adrenergic receptors in this area of any model organism. We recently reported high levels of D1 and D2 dopamine receptor expression in pyramidal neurons, particularly long-range pyramidal neurons in the FEF (Mueller et al, 2020). Other work has shown a colocalization of D1 dopamine receptors and α1 adrenergic receptors in the PFC (Mitrano et al, 2014;reviewed in Xing et al, 2016).…”

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

“…In our large-scale model, VIP/CR cells selectively disinhibited the dendrites of cells selective to the target stimulus, allowing target-related activity to flow through the cortical network. D1 receptors in monkey cortex are more strongly expressed on SST/CB neurons than other interneuron types (Mueller et al 2019), and application of dopamine to a frontal cortex slice increases inhibition to the dendrite, and decreases inhibition to the soma of pyramidal cells (Gao et al 2003). We found that, as long as local cortical areas (or potentially cortico-subcortical loops) are capable of maintaining persistent activity, then shifting the balance of inhibition from the soma to the dendrite can allow for maintenance of an active representation of a stimulus in persistent activity, while shielding it from distracting input from sensory areas.…”