The cognitive basis of intracranial self-stimulation of midbrain dopamine neurons

Abstract

Recently there has been a reckoning in the dopamine field. This has suggested that the dopamine prediction error may function as a teaching signal, without endowing preceding events with value. We studied the cognitive basis of intracranial self-stimulation (ICSS), a setting where dopamine appears to be valuable. Physiological frequencies seen during reinforcement learning did not support robust ICSS or promote behavior that would indicate the stimulation was represented as a meaningful reward in a specific or general sense. This was despite demonstrating that this same physiologically-relevant signal could function as a teaching signal. However, supraphysiological frequencies supported robust ICSS where the stimulation was represented as a specific sensory event, which acted as a goal to motivate behavior. This demonstrates that dopamine neurons only support ICSS at supraphysiological frequencies, and in a manner that does not reflect our subjective experience with endogenous firing of dopamine neurons during reinforcement learning.

A novel hypothalamic-midbrain circuit for model-based learning

“…Normally, rats will not learn about the novel auditory cues because no new information can be attributed them as there is no change in reward identity or magnitude (i.e., blocking) 70 . However, during one of the rewards, we stimulated VTA DA terminals in LH as a prediction error by delivering blue light into LH (1-sec; 20Hz, 473nm, 14-16mW) 41, 42, 72 , to examine whether we could facilitate learning about one of the auditory cues (“unblocked”) while the other cue would serve as a control is not learned about (“blocked”). As we and others have previously shown that light alone in eYFP controls does not unblock learning using these parameters 30, 41, 42, 71 , we opted for a within-subjects blocking design where all rats had ChR2 infused into VTA DA neurons which allowed us to compare responding to unblocked and blocked cues in each rat.…”

Theoretical Considerations for Optimizing the Use of Optogenetics with Complex Behavior

“…Additional evidence suggests that stimulating the same neuronal population at different frequencies could influence different types of behavior. Recent research examined whether rats would press a lever to optogenetically self‐stimulate dopamine neurons in the ventral tegmental area (Millard et al., 2022). The findings indicate that rats pressed a lever for 50 Hz neuronal stimulation but not for 20 Hz stimulation, even though 50 Hz stimulation exceeds the physiological limits of the spiking capabilities of the neurons.…”

Rewarding Value or Prediction Error: Settling the debate over the role of dopamine in reward learning

“…It is incontrovertible that VTA DA stimulation acts as a reinforcing signal for actions and states (e.g., Olds & Milner, 1954; Wise, 1978; Schultz et al, 1997). Animals readily self-stimulate for, and frequent places where, electrical or optogenetic activation of VTA DA neurons occurred, and disrupting this activity prevents learning or reduces established reward-seeking responses (e.g., Carter et al, 2022; Corbett & Wise, 1980; Crow, 1972; Ilango et al, 2014; Pascoli et al, 2015; Phillips & Fibiger, 1973; Millard et al, 2022; Witten et al, 2010). An intuitive interpretation of these findings is that VTA DA activity constitutes an appetitive event that is intrinsically rewarding.…”