Comparing phasic dopamine dynamics in the striatum, nucleus accumbens, amygdala, and medial prefrontal cortex

Abstract

Midbrain dopaminergic neurons project to and modulate multiple highly interconnected modules of the basal ganglia, limbic system, and frontal cortex. Dopamine regulates behaviors associated with action selection in the striatum, reward in the nucleus accumbens (NAc), emotional processing in the amygdala, and executive functioning in the medial prefrontal cortex (mPFC). The multifunctionality of dopamine likely occurs at the individual synapses, with varied levels of phasic dopamine release acting on different receptor populations. This study aimed to characterize specific aspects of stimulation-evoked phasic dopamine transmission, beyond simple dopamine release, using in vivo fixed potential amperometry with carbon fiber recording microelectrodes positioned in either the dorsal striatum, NAc, amygdala, or mPFC of anesthetized mice. To summarize results, the present study found that the striatum and NAc had increased stimulation-evoked phasic dopamine release, faster dopamine uptake (leading to restricted dopamine diffusion), weaker autoreceptor functioning, greater supply levels of available dopamine, and increased dopaminergic responses to DAT blockade compared to the amygdala and mPFC. Overall, these findings indicate that phasic dopamine may have different modes of communication between striatal and corticolimbic regions, with the first being profuse in concentration, rapid, and synaptically confined and the second being more limited in concentration but longer lasting and spatially dispersed. An improved understanding of regional differences in dopamine transmission can lead to more efficient treatments for disorders related to dopamine dysfunction. K E Y W O R D Samperometry, amygdala, autoreceptors, dopamine, nucleus accumbens, phasic, prefrontal cortex, striatum, uptake | INTRODUC TI ONNeural modules involved in emotion, reward, executive functions, and action selection are all regulated by the same chemical signal, bursts of dopamine, which originate from neuronal firing deep within the midbrain (Schultz, 2010). Dopaminergic axons from the midbrain are distributed to multiple brain regions in two independent, parallel circuits, the nigrostriatal and mesocorticolimbic dopamine pathways, each projecting to many highly interconnected modules of the basal ganglia, limbic system, and frontal cortex. The modules and their interconnecting feedback networks make up larger systems termed the motor, motivational, and associative corticostriatal loops, independent neural networks

Risky Decision-Making Predicts Dopamine Release Dynamics in Nucleus Accumbens Shell

“…MFB stimulation successfully induced dopamine efflux in all subjects. Additionally, the range of baseline dopamine release in the NACs (0.62 ± 0.08 µM) and the percent increase in intra-NAC dopamine release following nomifensine administration (322.53 ± 60.48 %) were similar to previous studies Holloway et al, 2019). Analyses revealed significantly elevated dopamine release in risk-taking rats relative to risk averse rats (t(17) = 3.85, p < .001; Figure 6 A -C).…”

Indirect and Direct Cannabinoid Agonists Differentially Affect Mesolimbic Dopamine Release and Related Behaviors

“…Dopamine autoreceptor sensitivity: Autoreceptor sensitivity was analyzed across pretreatment conditions as previously described [76,78,79]As seen in Figure 3C, there was not a main effect of drug pretreatment on autoreceptor sensitivity, F(2,50) = 1.66, p = .20, ηp 2 = .06.…”

“…Coronal sections of each brain were sliced at -30°C using a cryostat, and electrode placements were identified using a light microscope and marked on coronal diagrams [69]. Following the experiment, in vitro electrode calibration occurred by recording in solutions of dopamine (0.2 µM -1.2 µM) via a flow injection system [75][76][77], which allowed for the conversion of current measurements to dopamine concentrations.…”

“…DAR sensitivity was assessed by applying a pair of test stimuli (T1 and T2), with a varying number of conditioning pre-pulses prior to T2. Autoreceptor-mediated inhibition of evoked dopamine release was expressed in terms of the percent change between test stimulations (T2/T1x100) for each set of pre-pulses[76,78,79]. A two-way mixed ANOVA was used to assess the impact of pretreatment (AA-5-HT, ACEA, or vehicle) and number of pre-pulses on percent inhibition.…”

Midbrain dopaminergic inputs gate amygdala intercalated cell clusters by distinct and cooperative mechanisms

“…Phasic activity of midbrain dopaminergic neurons may signal unexpected rewards or aversive events such as noxious stimuli and these activity patterns shape DA release in target structures (Brischoux et al, 2009; Bromberg-Martin et al, 2010). Phasic stimulation (> 20 Hz) of VTA neurons increases DA release in forebrain structures, including amygdala, and affects behavior (Holloway et al, 2018; Tsai et al, 2009). In our hands, phasic but not tonic stimulation of midbrain dopaminergic inputs to dm-ITCs depressed sIPSC, suggesting that released DA modulates inhibitory transmission.…”