A new perspective on the brain's "Reward Molecule"

Research aimed at understanding how learning and memory processes are shaped in the brain has gained increasing significance in the field of neuroscience. A research team including Assist. Prof. Muhammet İkbal Alp, Vice Director of the Health Sciences and Technologies Research Institute at Istanbul Medipol University, and SABITA researcher Çağatay Aydın comprehensively evaluated existing studies examining how dopamine regulates learning and memory processes in different regions of the brain. The review study entitled“Dopaminergic Reciprocal Circuits for Learning and Memory”was published in the journal Neurobiology of Disease.

The study consolidated current experimental findings demonstrating that dopamine signals can produce distinct and sometimes even opposing effects depending on the brain region in which they are activated and the phase of learning during which they emerge. The research proposes a new conceptual framework that may contribute to understanding the mechanisms underlying neuropsychiatric disorders such as Alzheimer’s disease, schizophrenia, anxiety disorders, and post-traumatic stress disorder.

A NEW PERSPECTIVE ON THE ROLE OF DOPAMINE IN LEARNING
The research focuses on the dopamine system, which plays a critical role in the brain’s reward, motivation, and learning processes. In particular, the study comprehensively examined how dopamine signals originating from the brain region known as the ventral tegmental area (VTA) influence centres associated with learning and memory, including the prefrontal cortex, hippocampus, and amygdala.

For many years, scientists believed that dopamine functioned primarily as a “reward signal”. However, the new study demonstrates that dopamine is not solely associated with the sensation of reward; rather, it operates as a far more complex system that determines which information will be stored in memory, which behaviours will be suppressed, and which memories will be updated.

The researchers describe this mechanism as a “phase-by-target” model, namely a framework operating according to the phase of learning and the target brain region. Accordingly, dopamine assumes different functions in different regions of the brain. While it facilitates the encoding of new information into memory within the hippocampus, it regulates attention and behavioural control in the prefrontal cortex and enables the restructuring of fear- and reward-related memories in the amygdala.

THE SAME DOPAMINE SIGNAL CAN PRODUCE DIFFERENT OUTCOMES 
One of the study’s most striking findings was the collective evaluation of research demonstrating that the same dopamine signal can generate completely opposing behavioural outcomes in different neural circuits of the brain. According to the reviewed studies, certain signals strengthen fear memory, whereas others suppress fear responses.

Particularly noteworthy are the findings concerning fear learning and fear extinction processes. The researchers state that dopamine strengthens threat perception in certain neural circuits while supporting the sense of safety in others. This phenomenon may help explain why post-traumatic stress disorder and anxiety disorders become more persistent in some individuals.

The study also indicated that experimental findings demonstrating the important role of dopamine in the brain’s process of learning stimuli perceived as safe were evaluated. In particular, dopamine activity within the prefrontal cortex was reported to facilitate the brain’s acquisition of “absence of danger” information. It was emphasised that disruption of this mechanism may lead to excessive anxiety and fear responses.

THE EFFECT OF DOPAMINE ON MEMORY FORMATION
The study also addressed in detail the effects of dopamine signals reaching the hippocampus on memory formation. The findings demonstrated that dopamine plays a critical role particularly in the encoding of novel, attention-grabbing, or emotionally significant information into memory.

Experiments evaluated within the study showed that increasing dopamine activity in the hippocampus strengthens contextual memory. Dopamine was reported to play a decisive role particularly in spatial learning and the retention of environmental information in memory. According to the researchers, dopamine assists the brain in determining which information is “important” and supports the transfer of such information into long-term memory.

The study additionally noted that findings indicating dopamine’s influence not only on memory formation but also on memory consolidation were evaluated. It was stated that memory replay processes occurring during sleep are likewise supported by dopamine, thereby contributing to the permanence of learned information.

A CRITICAL ROLE IN DECISION-MAKING AND BEHAVIOURAL CONTROL
The research also includes important evaluations concerning dopamine’s effects on the prefrontal cortex. It was stated that maintaining balanced dopamine levels in the prefrontal cortex, one of the brain regions responsible for decision-making, attention management, and working memory, is critical for cognitive performance.

According to the research, excessively elevated dopamine levels may increase impulsive behaviours, whereas insufficient dopamine activity may lead to attention deficits, difficulty in decision-making, and loss of cognitive flexibility. The study emphasised that this condition may be associated with the cognitive impairments observed particularly in disorders such as schizophrenia and attention deficit/hyperactivity disorder.

The researchers also note that the timing of dopamine signals is of great importance. It was stated that dopamine activity occurring at the appropriate moment supports learning, whereas inappropriate timing may negatively affect memory performance.

CIRCUITS EXAMINED THROUGH OPTICAL AND GENETIC METHODS
The study comprehensively evaluated data obtained through optogenetic and chemogenetic methods, which have become increasingly widespread in neuroscience research in recent years. Through these techniques, researchers are able to control specific nerve cells using light or chemical methods, thereby examining in greater detail the role of different brain circuits in learning processes.

The experimental findings obtained through these methods were collectively analysed in order to comparatively evaluate the effects of dopamine circuits on learning, memory, fear, reward, and behavioural control. In this way, it was demonstrated that many findings previously considered independent from one another could be explained within a common framework.

A NEW APPROACH FOR NEUROPSYCHIATRIC DISORDERS
The research indicates that disruptions in dopamine circuits may produce significant consequences not only in terms of basic neuroscience but also from a clinical perspective. The study evaluated existing findings suggesting that irregularities in the dopamine system may directly affect learning and memory processes in disorders such as Alzheimer’s disease, schizophrenia, depression, anxiety disorders, and post-traumatic stress disorder.

According to the researchers, current treatment approaches generally focus on increasing or decreasing dopamine levels in a broad and non-specific manner. However, the proposed model evaluates studies demonstrating that each region of the brain responds differently to dopamine signals within a common framework, thereby paving the way for the development of more targeted treatment strategies. This approach is considered capable of contributing to the future development of personalised neuropsychiatric treatments.

PROVIDING A NEW FRAMEWORK FOR THE LITERATURE
One of the study’s most significant contributions lies in its reassessment of existing research concerning dopamine’s role in learning and memory processes beyond the conventional one-dimensional “reward system” perspective. The review consolidates findings indicating that dopamine functions as a multilayered “teaching signal” governing different phases of learning across distinct regions of the brain.

The “phase-by-target” model proposed by the researchers aims to explain within a common framework numerous findings that had previously appeared contradictory in the literature. The study evaluates existing scientific evidence demonstrating that dopamine is not associated solely with the sensation of reward but also plays a decisive role in processes such as memory formation, fear regulation, behavioural selection, and the updating of memories.

In this respect, the study offers a holistic perspective on the existing literature concerning learning and memory mechanisms while also presenting new evaluations regarding the biological processes underlying neuropsychiatric disorders. The findings addressed in the research are considered capable of guiding future targeted treatment strategies and new neuroscience studies.