Distinct prestimulus and poststimulus activation of VTA neurons correlates with stimulus detection

Abstract

Dopamine neurons of the ventral tegmental area (VTA) signal the occurrence of a reward-predicting conditioned stimulus (CS) with a subsecond duration increase in post-CS firing rate. Important theories about reward-prediction error and reward expectancy have been informed by the substantial number of studies that have examined post-CS phasic VTA neuron activity. On the other hand, the role of VTA neurons in anticipation of a reward-predicting CS and analysis of prestimulus spike rate rarely has been studied. We recorded from the VTA in rats during the 3-choice reaction time task, which has a fixed-duration prestimulus period and a difficult-to-detect stimulus. Use of a stimulus that was difficult to detect led to behavioral errors, which allowed us to compare VTA activity between trials with correct and incorrect stimulus-guided choices. We found a sustained increase in firing rate of both putative dopamine and GABA neurons during the pre-CS period of correct and incorrect trials. The poststimulus phasic response, however, was absent on incorrect trials, suggesting that the stimulus-evoked phasic response of dopamine neurons may relate to stimulus detection. The prestimulus activation of VTA neurons may modulate cortical systems that represent internal states of stimulus expectation and provide a mechanism for dopamine neurotransmission to influence preparatory attention to an expected stimulus.

Cognitive Neurostimulation: Learning to Volitionally Sustain Ventral Tegmental Area Activation

“…Although a dichotomized view of dopamine neuron physiology as either tonic or phasic has guided the field for many years, converging evidence across methodologies (Fiorillo et al, 2003; Howe et al, 2013; Totah et al, 2013) suggests a third type of dopamine response profile: a sustained, ramping signal evident during anticipation of reward. This ramping signal is distinct from rapid phasic responses, but also differs from tonic signals theorized to reflect a summation of prior phasic events (Niv et al, 2007) or spontaneous firing (Goto et al, 2007); instead, it appears more consistent with sustained excitatory inputs.…”

“…We predicted that volitional cognitive strategies—distinct from responses to external incentives—would correspond to a sustained temporal profile of activation, paralleling non-transient changes in animals during anticipation of extrinsic reward and cues (Fiorillo et al, 2003; Howe et al, 2013; Totah et al, 2013). Blood oxygen level-dependent (BOLD) fMRI signal increases in the midbrain, including VTA, have been shown to correlate with striatal dopamine release (Schott et al, 2008).…”

Mechanisms of motivation–cognition interaction: challenges and opportunities

“…Interestingly, recent evidence from microdialysis has demonstrated tonic dopamine efflux correlated with long-term average reward rates selectively in PFC terminal regions, but not the nucleus accumbens (St Onge, Ahn, Phillips, & Floresco, 2012). Other work has shown tonic dopamine release, as well as sustained firing of dopamine neurons, under conditions related to anticipatory, sustained motivated behaviors (Fiorillo, Tobler, & Schultz, 2003; Howe, Tierney, Sandberg, Phillips, & Graybiel, 2013; Totah, Kim, & Moghaddam, 2013). These dopamine-mediated effects of sustained motivation on response vigor are just beginning to be examined in humans (Beierholm et al, 2013).…”

Reward Anticipation Dynamics during Cognitive Control and Episodic Encoding: Implications for Dopamine

“…Reward anticipation prior to target in Chiew and Braver’s Early Incentive condition (Experiment 2) and object encoding in Stanek et al’s Late Epoch both correspond to the timescale associated with prolonged, ramp-like DA responses during reward anticipation: 2–8 s (Fiorillo et al, 2003; Howe et al, 2013; Totah et al, 2013). In contrast, reward anticipation prior to target in Chiew and Braver’s Late Incentive condition (Experiment 2) and object encoding in Stanek et al’s (submitted) Early Epoch both correspond to the timescale for phasic DA following reward cue (<500 ms; Schultz et al, 1997).…”