Dopamine modulation of prefrontal cortex activity is manifold and operates at multiple temporal and spatial scales

Abstract

While the function of dopamine in subcortical structures is largely limited to reward and movement, dopamine neurotransmission in the prefrontal cortex (PFC) is critical to a multitude of temporally and functionally diverse processes such as attention, working memory, behavioral flexibility, action selection, and stress adaptation. How does dopamine influence PFC computation of multiple temporally diverse functions? Here we find causation between sustained and burst patterns of phasic dopamine neuron activation and contemporaneous modulation of PFC neuronal activity at multiple spatio-temporal scales. These include a multidirectional and weak impact on individual PFC neuron rate activity and a robust influence on coordinated ensemble activity, gamma oscillations, and gamma-theta coupling that persisted for minutes. In addition, PFC network responses to burst pattern of dopamine firing were selectively strengthened in behaviorally active states. Thus, dopamine modulation of PFC is spatiotemporally diverse and is dictated by the pattern of dopamine neuron activation and behavioral state. These findings provide insight on the multiplex pattern of modulation by dopamine that may influence PFC computation of temporally diverse functions.

Neuromodulation in Psychiatric disorders: Experimental and Clinical evidence for reward and motivation network Deep Brain Stimulation: Focus on the medial forebrain bundle

“…These studies indicate the complexity of the regulation of dopamine neuron firing, which could be dependent on the type of stressors or severity of the stress and suggests that it is highly context‐dependent (Ungless et al., 2004; Valenti et al., 2012). Phasic optogenetic stimulation of VTA dopamine neurons was also reported to influence mPFC ensemble activity and behaviourally active states (grooming, rearing, locomotion), additionally enhancing beta‐activity at a transient time scale (milliseconds) and high gamma activity at a prolonged time scale (minutes; Lohani et al., 2019).…”

Dopamine transporter is a master regulator of dopaminergic neural network connectivity

“…However, as the experiments were performed in a cocktail of antagonists, future experiments will be necessary to provide more nuanced interpretations to the regulation of dopaminergic networks through simultaneous polypharmacy approaches of multiple targets that have been shown to alter network synchrony 142 . Importantly, while acute midbrain slices provide regional investigations into the regulatory mechanisms within each region, they do not account for active afferent input during behavioral state-dependent changes observed in freely behaving animals [143][144][145] . Therefore, future experiments will require in-vivo monitoring of network activity to determine whether and how dopaminergic networks of the SNC and VTA shift their topology to produce or respond to state-dependent changes.…”

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“…Neurons that exhibited short-latency excitatory responses to optogenetic stimulation were positively identified as PT neurons ( Figure 2D). All PT neurons exhibited action potential properties that are typical of cortical pyramidal neurons (Mitchell et al, 2007;Kaufman et al, 2010;Takahashi et al, 2015;Lohani et al, 2019) ( Figure 2-supplement 2). The proportion of PT neurons that exhibited short-latency responses to optogenetic activation and the latency of those evoked responses ( Table 2) were similar in Q175 and WT mice.…”