Dopamine's Reach Into the Primate Parietal Attention Network

Dopamine's role in attention has mostly been studied in the frontal lobe. A Newcastle University team went looking for it in the parietal cortex instead, delivering the drug directly onto the very neurons they were recording from in awake macaques.

Ask a neuroscientist where dopamine acts on attention and the answer will usually start with the frontal lobe. 

Decades of work on the prefrontal cortex and basal ganglia have built solid, clinically useful models linking dopamine to executive control and motor function — models detailed enough to inform treatment for Parkinson's disease, ADHD and schizophrenia. 

The posterior parietal cortex (PPC) has had a much quieter role in that story, despite sitting at the centre of the fronto-parietal networks that support selective attention.

Part of the reason is a species gap in the evidence. In rodents, dopaminergic innervation of parietal areas is sparse, which has made the region a low priority for dopamine research built largely on rodent models. 

Primates are different: tracing studies have shown that macaque PPC carries dopamine transporter-immunoreactive axons at a density comparable to prefrontal cortex, and human imaging work has found dense dopamine receptor expression in the same region, with drugs targeting those receptors and transporters measurably affecting parietal activity in clinical populations. The anatomy and the pharmacology both pointed somewhere that hadn't been tested directly at the level of single neurons.

Testing it directly is not straightforward. 

It means delivering dopamine, or a receptor-selective drug, to a small, specific patch of cortex in an awake, behaving animal, while recording the electrical activity of the very neurons receiving the drug — and doing this cleanly enough to rule out the recording method itself as the source of any effect. 

A research team at Newcastle University's Biosciences Institute, working with collaborators at Ruhr University Bochum and Monash University, set out to do exactly this in macaque intraparietal sulcus, a core part of PPC, while the animals performed a spatial attention task.

They recorded from 88 single- and multi-units while iontophoretically applying either dopamine itself or SCH23390, a selective antagonist of the D1 dopamine receptor, directly into the cortical tissue around the recording site. Fifty-nine units were tested with dopamine, twenty-nine with the antagonist, and — critically — a separate set of control recordings used pH-matched saline to check that the act of applying current and fluid near a neuron wasn't itself distorting the signal.

The results were clear on that point: saline controls showed no systematic effect on firing, which meant the drug effects that did appear could be attributed to the drugs. Dopamine reduced firing rates across the population, following an inverted U-shaped relationship with dose — moderate ejection currents produced the strongest inhibition, a pattern already familiar from dopamine's effects in prefrontal cortex. SCH23390 reduced firing too, but along a simple monotonic curve rather than an inverted U, implying the two drugs act through at least partly distinct mechanisms. Both drugs also increased gain variability — a measure of trial-to-trial excitability fluctuation independent of mean firing rate — and both reduced the pupillary light reflex, a physiological readout that extended the effect beyond the cortical circuit being recorded from. 

Roughly half of the units modulated by drug application were also modulated by attention itself, giving the first direct electrophysiological evidence that dopamine shapes activity in a primate attention network outside the frontal lobe.

Getting a drug and a recording electrode into the same few cubic micrometres of living cortex, repeatedly, across two animals and many sessions, is an engineering problem as much as a neuroscience one. The team built its own electrode-pipettes for the job: a sharpened tungsten wire, 125 micrometres in diameter and 75 millimetres long, threaded through a three-barrel borosilicate glass capillary alongside the drug-filled channels used for iontophoresis. The wire — supplied by Advent Research Materials, UK — was electrolytically etched to a fine point, then the glass was drawn down around it on a microelectrode puller, with the assembly secured by filling the central barrel with superglue. 

The paper notes, in passing, why that last step mattered: without it, the free length of tungsten wire inside the glass could resonate with small movements of the animal, introducing noise into an otherwise clean recording.

That detail is worth dwelling on, as our own reading rather than a finding the paper sets out to make. It's a reminder that a combined iontophoresis-and-recording electrode, however carefully designed on paper, is ultimately a hand-built object assembled from a handful of very ordinary materials — glass capillary, epoxy, a length of metal wire — and that its electrical cleanliness depends on getting the mechanical details of that assembly right before the pharmacology ever begins. 

The broader result here — that dopamine's reach extends into parietal cortex, and does so through at least two pharmacologically distinct pathways — adds a primate parietal chapter to a story about neuromodulation of attention that has mostly been told from the frontal lobe. 

It also serves as a useful reminder that in systems neuroscience, the instrument and the experiment are rarely separable: a result this specific, about dose-response curves and gain variability in single cortical units, rests on an apparatus built from parts trusted enough not to think about, until something goes wrong.

Source

Title: Dopamine influences attentional rate modulation in Macaque posterior parietal cortex
Journal: Scientific Reports
Authors: Jochem van Kempen, Christian Brandt, Claudia Distler, Mark A. Bellgrove, Alexander Thiele
Published: 28 April 2022
DOI: 10.1038/s41598-022-10634-w

Abstract: Cognitive neuroscience has made great strides in understanding the neural substrates of attention, but our understanding of its neuropharmacology remains incomplete. Although dopamine has historically been studied in relation to frontal functioning, emerging evidence suggests…