Mesocorticolimbic system The
mesocorticolimbic system (
mesocorticolimbic circuit) refers to both the
mesocortical and
mesolimbic pathways. Both pathways originate at the ventral tegmental area (VTA) which is located in the midbrain. Through separate connections to the prefrontal cortex (mesocortical) and ventral striatum (mesolimbic), the mesocorticolimbic projection has a significant role in learning, motivation, reward, memory and movement. Dopamine receptor subtypes, D1 and D2 have been shown to have complementary functions in the mesocorticolimbic projection, facilitating learning in response to both positive and
negative feedback. Both pathways of the mesocorticolimbic system are associated with
ADHD,
schizophrenia and
addiction.
Mesocortical pathway The
mesocortical pathway projects from the ventral tegmental area to the prefrontal cortex (
VTA →
Prefrontal cortex). This pathway is involved in cognition and the regulation of
executive functions (e.g., attention, working memory,
inhibitory control, planning, etc.) This intricate neural circuit serves as a crucial communication route within the brain, facilitating the transmission of dopamine, a neurotransmitter associated with reward, motivation, and cognitive control. The prefrontal cortex, being a central hub for executive functions, relies on the input from the mesocortical pathway to modulate and fine-tune cognitive processes essential for goal-directed behavior and decision-making. Dysregulation of the neurons in this pathway has been connected to ADHD. The mesolimbic pathway is involved with
incentive salience,
motivation, reinforcement learning, fear and other cognitive processes. In animal studies, depletion of dopamine in this pathway, or lesions at its site of origin, decrease the extent to which an animal is willing to go to obtain a reward (e.g., the number of lever presses for nicotine or time searching for food).
Nigrostriatal pathway The
nigrostriatal pathway is involved in behaviors relating to movement and motivation. The transmission of dopaminergic neurons to the
dorsal striatum particularly plays a role in reward and motivation while movement is influenced by the transmission of dopaminergic neurons to the substantia nigra. The nigrostriatal pathway is associated with conditions such as Huntington's disease, Parkinson's disease, ADHD, Schizophrenia, and Tourette's Syndrome. Huntington's disease, Parkinson's disease, and Tourette's Syndrome are conditions affected by motor functioning while schizophrenia and ADHD are affected by reward and motivation functioning. This pathway also regulates associated learning such as classical conditioning and operant conditioning.
Tuberoinfundibular pathway The
tuberoinfundibular pathway transmits dopamine from the
hypothalamus to the
pituitary gland. This neural circuit plays a pivotal role in the regulation of hormonal balance and, specifically, in modulating the secretion of prolactin from the pituitary gland, which is responsible for breast milk production in females. Hyperprolactinemia is an associated condition caused by an excessive amount of prolactin production that is common in pregnant women. After childbirth, the tuberoinfundibular pathway resumes its role in regulating prolactin levels. The decline in estrogen levels postpartum contributes to the restoration of dopaminergic inhibition, preventing sustained hyperprolactinemia in non-pregnant and non-nursing individuals.
Cortico-basal ganglia-thalamo-cortical loop The dopaminergic pathways that project from the
substantia nigra pars compacta (SNc) and
ventral tegmental area (VTA) into the
striatum (i.e., the nigrostriatal and mesolimbic pathways, respectively) form one component of a sequence of pathways known as the
cortico-basal ganglia-thalamo-cortical loop. The nigrostriatal component of the loop consists of the SNc, giving rise to both inhibitory and excitatory pathways that run from the striatum into the
globus pallidus, before carrying on to the thalamus, or into the
subthalamic nucleus before heading into the
thalamus. The dopaminergic neurons in this circuit increase the magnitude of phasic firing in response to positive reward error, that is when the reward exceeds the expected reward. These neurons do not decrease phasic firing during a negative reward prediction (less reward than expected), leading to hypothesis that serotonergic, rather than dopaminergic neurons encode reward loss. Dopamine phasic activity also increases during cues that signal negative events, however dopaminergic neuron stimulation still induces place preference, indicating its main role in evaluating a positive stimulus. From these findings, two hypotheses have developed, as to the role of the basal ganglia and nigrostriatal dopamine circuits in action selection. The first model suggests a "critic" which encodes value, and an actor which encodes responses to stimuli based on perceived value. However, the second model proposes that the actions do not originate in the basal ganglia, and instead originate in the cortex and are selected by the basal ganglia. This model proposes that the direct pathway controls appropriate behavior and the indirect suppresses actions not suitable for the situation. This model proposes that tonic dopaminergic firing increases the activity of the direct pathway, causing a bias towards executing actions faster. These models of the basal ganglia are thought to be relevant to the study of
OCD,
ADHD,
Tourette syndrome,
Parkinson's disease,
schizophrenia, and
addiction. For example,
Parkinson's disease is hypothesized to be a result of excessive inhibitory pathway activity, which explains the slow movement and cognitive deficits, while Tourettes is proposed to be a result of excessive excitatory activity resulting in the tics characteristic of Tourettes. ==Regulation==