Dopamine Regulates Two Classes of Primate Prefrontal Neurons That Represent Sensory Signals

Abstract

The lateral prefrontal cortex (PFC), a hub of higher-level cognitive processing, is strongly modulated by midbrain dopamine (DA) neurons. The cellular mechanisms have been comprehensively studied in the context of short-term memory, but little is known about how DA regulates sensory inputs to PFC that precede and give rise to such memory activity. By preparing recipient cortical circuits for incoming signals, DA could be a powerful determinant of downstream cognitive processing. Here, we tested the hypothesis that prefrontal DA regulates the representation of sensory signals that are required for perceptual decisions. In rhesus monkeys trained to report the presence or absence of visual stimuli at varying levels of contrast, we simultaneously recorded extracellular single-unit activity and applied DA to the immediate vicinity of the neurons by micro-iontophoresis. We found that DA modulation of prefrontal neurons is not uniform but tailored to specialized neuronal classes. In one population of neurons, DA suppressed activity with high temporal precision but preserved signal/noise ratio. Neurons in this group had short visual response latencies and comprised all recorded narrow-spiking, putative interneurons. In a distinct population, DA increased excitability and enhanced signal/noise ratio by reducing response variability. These neurons had longer visual response latencies and were composed exclusively of broad-spiking, putative pyramidal neurons. By gating sensory inputs to PFC and subsequently strengthening the representation of sensory signals, DA might play an important role in shaping how the PFC initiates appropriate behavior in response to changes in the sensory environment.

Tonic effects of the dopaminergic ventral midbrain on the auditory cortex of awake macaque monkeys

“…This difference between the driven firing and the evoked response could be very well explained by the changes of the spontaneous firing that were also induced by the electrical stimulation. Our findings are compatible with the observations in the prefrontal cortex of rodents (Jacob et al 2013). This suggests that electrical stimulation of the dopaminergic ventral midbrain does not modify the synaptic weight of the suprathreshold lemniscal inputs to auditory cortex.…”

“…The most likely candidate is dopamine because it is known that increases of the level of this transmitter in cerebral cortex (Lavin et al 2005;Jacob et al 2013) or in auditory subcortical structures (Garcia-Cabezas et al 2007;Gittelman et al 2013) cause decreases in spontaneous firing on a timescale of Fig. 3 Effects of electrical stimulation of the dopaminergic ventral midbrain on auditory evoked potentials.…”

“…The two mechanisms may have different effects on auditory cortex when subjects are engaged in an auditory task in which different task elements have different salience. When salience-related changes of dopamine affect only the driven firing by decreasing the spontaneous firing, the width of the neurons' receptive field could be changed for auditory stimuli (Silver 2010;Wilson et al 2012;Jacob et al 2013). When the dopamine affects the evoked firing only, the strength of the neurons' response could be altered (Silver 2010;Wilson et al 2012;Jacob et al 2013).…”

Dopamine-Induced Dissociation of BOLD and Neural Activity in Macaque Visual Cortex

“…DA has been shown to improve the SNR in prefrontal cortex (PFC) and in sensory areas, including V1 [8,[14][15][16], thereby changing detection performance at the behavioral level [8,[16][17][18]. Increased neuronal activity in V1 has been shown to predict the timing of reward delivery, even when the cells were not driven by a visual stimulus [8,18], highlighting the importance of DA for extracting behaviorally relevant information [17,19].…”

“…The increase in neural activity upon systemic DA may be mediated by longrange interactions from higher-order regions (e.g., frontal regions) [5,15]. Large-scale interactions have been reported in other sensory modalities, including the visual, somatosensory, and auditory systems, suggesting that DA prepares the higherorder area for the processing of incoming sensory signals and promotes the readout of task-related information [14][15][16]. Manipulation of prefrontal D1 receptors increased the magnitude, reliability, and selectivity of neuronal responses in V4 [5], and similar mechanisms may play a role in V1.…”