Since time immemorial, animals have sought rewarding stimuli that result in pleasant sensations. In the animal kingdom, the pursuit of rewards, such as water, food, and sex, among others, is closely linked to the survival of the individual and the species as a whole. The stimuli that lead to such actions are intrinsic or unconditioned stimuli (US). These stimuli lead to a natural pleasurable response, also known as the unconditioned response (UR). These stimuli are intrinsically present, while other stimuli must first be learned to result in a reward. We call these extrinsic or conditioned stimuli (CS), such as work that must be rewarded with money (conditioned response or CR). In order for an organism to form this connection, a CS normally occurs in conjunction with a US during a training phase. From a scientific perspective, reward seeking induces specific behaviors in an organism. We can therefore discern different functions for reward seeking. Dopamine has long been implicated in motivation, learning, and reward seeking. These behavioral processes are intimately linked to each other and it has been shown that different areas of the brain play a vital role in these processes. To further increase the complexity and confusion of the system, other pathways overlap with the dopaminergic system such as the serotonergic, cholinergic, GABAergic, orexinergic, and noradrenergic system. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay The interaction of anatomically distinct brain areas in the dopaminergic system gives rise to different types of learning and motivation phases. Ventral tegmental area and reward prediction error The ventral tegmental area (VTA) is a key area in the mesocorticolimbic dopaminergic system. The VTA receives input from sensory systems, and its dopaminergic neurons project to several other brain structures involved in motivation and learning, such as the core and shell of the nucleus accumbens and the prefrontal cortex. The VTA shows strong dopaminergic activity during reward-related learning in the form of phasic DA pulses. In the pioneering study by Schulz et al. (1997), it was shown that a significant increase in dopamine levels occurred in the VTA of the monkey brain during performance of a learning task initially after consumption of a reward. After the training phase, phasic dopamine impulses were already observed at the presentation of the first environmental cue (appearance of a light indicating to press the lever to obtain a reward), but phasic dopamine impulses decreased with consumption of the reward. On the other hand, it has generally been shown that elimination of dopamine signaling in the VTA and NAc (elimination of D2 receptors) is the basis of aversive learning. These phasic dopamine impulses are strongly related to reward-seeking behavior and learning. It is generally said that this pulsation of the DA neuron encodes a so-called “reward prediction error” (RPE). RPE is the actual value of a rewarding stimulus minus the expectation of the value of a rewarding stimulus. Therefore RPE can be divided into positive RPE, neutral RPE or negative RPE. A positive RPE indicates that the final reward was more pleasant than initially expected, which generally leads to learning, such that the environmental stimuli that lead to that reward are identified. A positive RPE can also originate from onesurprising positive reward. A neutral RPE indicates that the expected pleasant feeling of a reward was the same as the actual outcome. In a negative RPE, the reward was so to speak disappointing, i.e. the outcome was less satisfying. A negative RPE induces aversive learning to avoid future unpleasant or painful situations. Dorsal dopaminergic neurons in the VTA usually show decreased activation to noxious stimuli (foot shock), whereas increased activity can be observed in ventral dopaminergic neurons.neurons in the VTA. A foot shock was applied to the hind paw of anesthetized rats, and the activity of DA neurons in the dorsal and ventral VTA was recorded. In the figure above, we see an initial decrease in the activation of DA neurons in the dorsal VTA. A noxious stimulus inhibits this neural activity. In the figure below, there is a strong initial increase in DA neuron activation in the dorsal VTA. These neurons are excited by a noxious stimulus. Dopamine is not the only neurotransmitter that acts in the mesolimbic pathway. The mesolimbic dopamine pathway has been shown to be subject to cholinergic modulation and transient vanilloid 3 receptor potential in the VTA. Dopamine in the Nucleus Accumbens Core and Shell The Nucleus accumbens (NAc) is part of the mesolimbic pathway and receives input from the VTA. It is important to discern that the NAc core and NAc shell compute neural inputs for different types of learning. The NAc core also performs the RPE calculation while the NAc shell is involved in incentive salience. This can be confusing, as it appears that NAc shell activity usually shows high activity in incentive salience, whereas the NAc core is best studied with reward-related theories, although it is also active in incentive salience. Nucleus accumbens core measurements are represented by the bold black line, Nucleus accumbens shell measurements are represented by the bold gray line. DA neuron signaling was measured in the nucleus and shell of the Nucleus accumbens in mice during a lever pressing task. Peak values ​​are achieved by pressing the first lever (SLp) in the core and shell. As the mouse proceeds with the task, dopamine levels in the core rapidly drop to basal levels (with a smaller increase during the second lever press (TL0)), while dopamine signaling in the shell remains consistently elevated, exemplifying the its relevance in the incentive. salience. At the end of the task, dopamine signaling returned to baseline values. Dopamine in fear learning and extinctionThe amygdala is an indispensable component in fear learning and is necessary for the consolidation of memories associated with fear. It is also part of the mesolimbic pathway, as the VTA projects to the amygdala. Correct memory formation also involves other brain structures such as the hippocampus and the NAc. Fear conditioning is a very fast process in which a CS is paired with a shock US. For example, a sound (CS) occurs at the same time as a foot strike (US). Mice will show an aversive response to the foot shock, but initially the sound will not induce noticeable behavior in the mouse. After the training phase, the mouse will have established a connection between the sound and the foot shock (the sound predicts the foot shock), which will be sufficient to induce a fear response. The process of fear extinction describes the behavioral change of an animal to a CS, where the result is no fear response. This does not mean that the initial fear memory has been erased, but that the animal has adapted to its environmental situation (the RPE of the CS has become neutral)..