Brain mechanism for reward enjoyment

Anhedonia is the inability to gain pleasure from typically pleasurable experiences. It is a common characteristic amongst many individuals who suffer from depression, schizophrenia and some other mental illnesses. However, what causes the condition still remains unclear. A new study in the journal Neuron reveals that neuroscientists from the University of North Carolina at the Chapel Hill School of Medicine may have literally enlightened the answer, which could pave the way for discovering new mental health therapies. Researchers manipulated the wiring of a specific population of brain cells deep in a portion of a midbrain area, which is known to promote behavioral responses to reward by using a combination of genetic engineering and laser technology. Leading researcher, Garret D. Stuber, PhD, assistant professor in the departments of Psychiatry and Cell and Molecular Physiology, and the UNC Neuroscience Center declared: \"For many years it\'s been known that dopamine neurons in the ventral midbrain, the ventral tegmental area, or VTA, are involved in reward processing and motivation. For example, they\'re activated during exposure to drugs of abuse and to naturally rewarding experiences. The major focus in our lab is to determine what other sorts of neural circuits or genetically defined neural populations might be modulating the activity of those neurons, whether it\'s increasing or decreasing their activity. In our study we found that activation of the nearby VTA GABAergic neurons directly inhibit the function of dopamine neurons, which is something that\'s never been shown before.\" Researchers previously tried to get an insight into the brain\'s inner workings by using drugs or electrical stimulation. However, techniques like those were unable to rapidly and specifically alter just one particular type of cell or one type of connection in contrast to optogenetics, a novel technique discovered about six years ago. The authors inserted a foreign gene into the genome of a transgenic animal in order to express a bacterial enzyme, which can cause DNA recombination only in GABA neurons, but not in dopamine cells. The animal was anesthetized and the team used a gene transfer method developed at UNC to transfer light-sensitive proteins (opsins) into the VTA to target GABA cells. The opsins were derived from algae or bacteria that require light in order to grow, as they enabled the researchers to excite or prevent the foreign opsins in GABA neurons by \'feeding\' light from a laser into brain tissue. The animals were subsequently assessed in different reward situations, that consisted of simple tasks, whereby the animals were trained to link a cue with a reward of sugar water from a bottle, or, they were rewarded by \"free licking,\" which meant they could drink as much as they wanted. The researchers then activated light laser beams for 5 seconds onto the genetically manipulated GABA neurons during the cue period followed by reward, whilst on another day, they activated the neurons during reward consumption, when the animals were actively engaged in drinking the sugar water. Stuber explained: \"And what we saw when we activated the cells during the cue period, or reward anticipation, it didn\'t do anything to the behavioral response at all; they showed no difference compared to non-stimulated animals. And when they were actively engaging with the sucrose, we did see we could disrupt their reward consumption when we activated those cells. They immediately disengaged from drinking, stopped drinking the sucrose solution. And when the stimulus stopped, they would then return back and continue to drink it again.\" The findings revealed that optical stimulation of GABA neurons during the \"free licking\" sessions, resulted in disruption of sucrose consumption with the animals stopping to drink. The team was able to monitor the GABA and dompamine neurons\' activity by using high-tech electrophysiology and cell chemistry measures and discovered a direct association between GABA activation and dopamine suppression.