Reward behavior is a key topic of focus for both behavior psychologists and neuroscientists. From the neuroscience perspective, reward behavior is initiated by the synaptic activity of certain neurotransmitters in reward-oriented areas of the brain. The central area of focus for reward behavior research is called the ventral tegmental area (VTA), located in the midbrain. The VTA has different inputs from and outputs to cortical areas and the limbic system. Dopamine is the neurotransmitter of focus in the brain’s reward pathway. Studying the neurobiology behind reward processing is crucial for understanding addiction, motivation, and aversion. With a better understanding of the VTA and its function, scientists and pharmacologists will find more efficient ways to tackle the negative consequences of the reward pathway. Although much research has been done on the VTA, more findings are bringing us closer to the full mechanism of reward processing.
In the study, “Optogenetic excitation in the ventral tegmental area of glutamatergic or cholinergic inputs from the laterodorsal tegmental area drives reward,” Dr. Steidl et. al studied the optogenetic excitation of LDTg cholinergic neurons and LDTg glutamatergic neurons. These two types of neurons are located in VTA, and they control reward processing. The experiment involved only ChAT-IRES-Cre mice that were Cre+, and the mice were all males. Using stereotactic injections, the researchers injected adeno-associated viruses into the mice. They then used a plane procedure to expose the mice to situations with light so that their LDTg neurons can be stimulated when exposed to light. There were two groups of mice, the ChAT-ChR2-eYFP and ChAT-eYFP mice. The researchers used a chamber with light and a chamber without light. They were trying to monitor how long each mouse from each group spent in the light chamber and non-light chamber. Those that spent more time in the light chamber are more rewarded, which means light stimulation is causing synapses at the VTA (ventral tegmental area). Mice with LDTg-cholinergic neurons activated spent longer durations in a light-paired chamber. Mice with LDTg-glutamatergic neurons activated took many visits to the light-paired chamber. So, the researchers determined that both neuronal inputs induced reward-seeking behavior in different ways. The activated glutamatergic neurons caused the mice to replicate the behavior that gave them a rewarding feeling. On the other hand, the activated cholinergic neurons caused the mice to remain longer in a state that gave them a rewarding feeling. The optogenetic activation of these particular neuronal inputs never caused avoidance from the stimulus, which was the light chamber. However, optogenetic methods cannot help discover if these different neuronal inputs are co-activated or selectively activated for various forms of rewards. The researchers concluded that LDTg-glutamatergic neurons are crucial for initial decision making to receive a reward, while LDTg-cholinergic neurons are essential for maintaining rewarding behavior. Both LDTg-cholinergic and glutamatergic neurons are a central element in the reward processing mechanism located in the VTA.
In the study, “The Lateral Preoptic Area: A Novel Regulator of Reward Seeking and Neuronal Activity in the Ventral Tegmental Area,” Dr. Gordon-Fennell et. al discovered that the lateral preoptic area (LPO) has both direct and indirection projections to the VTA that can modulate the activity of the VTA. The LPO is an unexplored region within the hypothalamus. By controlling the activity of the VTA, the LPO has control over reward processing. In past studies, LPO was found to be involved in causing preferential behavior and locomotor activity. In this study, the researchers used male Sprague Dawley rats. They tested reward behavior in these rats using operant self-administration of either cocaine or sucrose or reward-seeking behavior of the same two stimuli. The greater the intake or search for stimuli, the stronger the reward behavior as induced by the LPO activation. The LPO region was activated using bicuculline, which is a GABA antagonist and inhibited by using a mix of baclofen and muscimol, which are GABA agonists. The researchers conducted five different experiments in this study. Each experiment studied both self-administration and reward-seeking behavior. The researchers found that when the LPO was stimulated, the reward-seeking behavior of the mice increased. The reward-seeking was examined by removing the stimulus and then seeing if the mice continued to seek the stimulus through their behavior. The researchers also compared the reward-seeking behavior between two different stimuli: cocaine and sucrose. Both stimuli yielded increases in reward-seeking behavior when paired with LPO stimulation even though cocaine is more addictive by nature. LPO activation, however, did not increase the operant self-administration of the mice. When scientists administered punishment to LPO activated mice, the mice's behavior was not altered by the punishment and thus did not avoid the stimulus. This result was not the case for regular mice who avoided the stimulus after punishment. Lastly, the researchers studied the projections of LPO that synapsed in the VTA. Both GABA and glutamate projections from the LPO are located in the VTA. Furthermore, there are indirect pathways by which LPO affects the VTA. This study could not find the exact mechanism of LPO on VTA. However, they found that LPO stimulation causes inhibition of GABA neurons and the enhancement of dopamine neurons in the VTA. This means that the LPO stimulation causes reward behavior. This research study focuses on the LPO, one of many regions in the brain, which modifies the activity of VTA and thus controls reward behavior.
Both of these studies looked at neuronal inputs and how the outward behavior changed following neuronal changes. Dr. Steidl and his fellow researchers directly stimulated two different types of neurons located within the VTA to test their effect on reward processing. Likewise, Dr. Gordon-Fennell and his fellow researchers tested the stimulation of LPO on reward behavior and its connection to the reward pathway located in the VTA. The results of both studies added to the puzzle of the reward system mechanism. There are many elements of this complex mechanism. Both studies used different means of stimulation, means of assessing reward behaviors, and locations of interest in the brain. They both concluded that the VTA and the projections that activate it are the keys to understanding reward processing. Many more research projects are being done and need to be analyzed to reach the full picture of the reward processing mechanism.
Citations
Gordon-Fennell AG, Will RG, Ramachandra V, et al. The Lateral Preoptic Area: A Novel Regulator of Reward Seeking and Neuronal Activity in the Ventral Tegmental Area. Front Neurosci. 2020;13:1433. Published 2020 Jan 17. doi:10.3389/fnins.2019.01433
Steidl, S., Wang, H., Ordonez, M., Zhang, S., & Morales, M. (2016). Optogenetic excitation in the ventral tegmental area of glutamatergic or cholinergic inputs from the laterodorsal tegmental area drives reward. European Journal of Neuroscience, 45(4), 559-571. doi:10.1111/ejn.13436
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