Tonic versus phasic DA release in the nucleus accumbens is differentially regulated by pathways that selectively alter DA neuron spontaneous activity and burst firing

Biological and Psychological Perspectives of Resilience: Is It Possible to Improve Stress Resistance?

“…DA neurons in the VTA mediate susceptibility and resilience in CSDS-induced behavioral abnormalities. VTA DA neurons exhibit low frequency tonic firing and high frequency phasic firing in vivo (Grace et al, 2003 ). Induction of phasic, but not tonic, firing by optogenetic stimulation in VTA DA neurons results in a susceptible phenotype in mice undergoing subthreshold CSDS, as indicated by social avoidance and decreased sucrose consumption.…”

Developmental Pathology, Dopamine, and Stress: A Model for the Age of Onset of Schizophrenia Symptoms

“…Based on evidence of cortical modulation of subcortical DA activity, a model of DA functioning in schizophrenia has been proposed (Grace 1991, 1993) that is compatible with both the hyper- and/or hypodopaminergic functioning and reduced glutamate activity at the NMDA receptor suggested in this disorder. This model posits that there are two modes by which DA is released in the striatum: phasic DA release, which is the transient high-amplitude release that results when the DA cell fires bursts of action potentials (burst firing) in response to behaviorally relevant stimuli; and tonic DA release, which is dependent on slow tonic DA neuron spike firing (Grace et al 2003), is proposed to be modulated by corticostriatal glutamatergic input, and largely drives extracellular DA concentrations. It is thought that because of its transient nature and rapid removal from the synaptic cleft by the DA transporter, phasic DA release contributes little to baseline extrasynaptic DA levels and is not likely to trigger compensatory mechanisms within the DA system (figure 2A).…”

“…Research suggests that exposure to a chronic stressor may result in a decrease or downregulation of the tonic activity of VTA DA neurons (e.g., chronic cold stressor; Moore et al 2001 b ); such an effect should result in decreased tonic DA levels in the nucleus accumbens (Grace et al 2003). Thus, it is possible that exposure of patients to chronic stress, including the stress that is likely to be associated with experiencing certain schizophrenia symptoms, could further exacerbate the subcortical DA dysregulation that is proposed to occur in this disorder.…”