The article on Basal Ganglia in the wikipedia points to Dopamine being a neuromodulator. So I am going to spend some time today and try to understand what is a neuromodulator, how it is different from a neurotransmitter (with the hope of better understanding how dopamine and GABA play a role in the functioning of the Basil Ganglia).

Neuromodulation in Wikipedia

Define: neuromodulators

In Neuromodulation several classes of neurotransmitters regulate diverse populations of central nervous system neurons (one neuron uses different neurotransmitters to connect to several neurons). This is in contrast to direct synaptic transmission, in which one presynaptic neuron directly influences a postsynaptic partner (one neuronreaching one other neuron), neuromodulatory transmitters secreted by a small group of neurons diffuse through large areas of the nervous system, having an effect on multiple neurons. Examples of neuromodulators include dopamineserotoninacetylcholinehistamine and others.

A neuromodulator is a relatively new concept. It can be conceptualized as a neurotransmitter that is not reabsorbed by the pre-synaptic neuron or broken down into a metabolite. Such neuromodulators end up spending a significant amount of time in the CSF (cerebrospinal fluid), influencing (or modulating) the overall activity level of the brain.

The dopamine system

Origin: dopamine pathways:

Targets: Dopamine receptors at pathway terminations.

Effects: motor systemreward systemcognitionendocrinenausea

Via the dopamine receptors, D1-5, dopamine reduces the influence of the indirect pathway, and increases the actions of the direct pathway within the basal ganglia. Insufficient dopamine biosynthesis in the dopaminergic neurons can cause Parkinson’s disease, in which a person loses the ability to execute smooth, controlled movements.

Define: pathway

A neural pathway, or neural tract, connects one part of the nervous system with another and usually consists of bundles of elongated, myelin-insulated neurons, known collectively as white matter. Neural pathways serve to connect relatively distant areas of the brain or nervous system, compared to the local communication of grey matter.

Define: indirect pathway of movement

The indirect pathway of movement is a neuronal circuit through the basal ganglia and several associated nuclei within the central nervous system (CNS) which helps to prevent unwanted muscle contractions from competing with voluntary movements[1]. It operates in conjunction with the direct pathway of movement.

The indirect pathway passes through the caudateputamen, and globus pallidus, which are parts of the basal ganglia[2]. It traverses the subthalamic nucleus, a part of the diencephalon, and enters the substantia nigra, a part of the midbrain. In a resting individual, a specific region of the globus pallidus, known as the internus, and a portion of the substantia nigra, known as the pars reticulata, send spontaneous inhibitory signals to the ventrolateral nucleus of the thalamus, through the release of GABA, an inhibitory neurotransmitter[3]. Inhibition of the excitatory neurons within VL, which project to the motor regions of the cerebral cortices of the telencephalon, leads to a reduction of activity in the motor cortices, and a lack of muscular action[4].

When the pre-frontal region of the cerebral cortex, which is generally involved in decision making and planning, determines that motor activity be executed, it sends activating signals to the motor cortices. The motor cortices send activating signals to the direct pathway through the basal ganglia, which stops inhibitory outflow from parts of the globus pallidus internus and the substantia nigra pars reticulate. The net effect is to allow the activation of the ventrolateral nucleus of the thalamus which, in turn, sends activating signals to the motor cortices. These events amplify motor cortical activity that will eventually drive muscle contractions.

Simultaneously, in the indirect pathway, the motor cortices send activating signals to the caudate and putamen. The cells of the indirect pathway in the caudate and putamen that receive these signals are inhibitory and, once activated, they send inhibitory signals to the globus pallidus externus, reducing the activity in that nucleus. The globus pallidus externus normally sends inhibitory signals to the subthalamic nucleus. On activation of the indirect pathway, these inhibitory signals are reduced, which allows more activation of the subthalamic nucleus. Subthalamic nucleus cells can then send more activating signals to some parts of the globus pallidus internus and substantia nigra pars reticulata. Thus, parts of these two nuclei are driven to send more inhibitory signals to the ventrolateral nucleus of the thalamus, which prevents the development of significant activity in the motor cerebral cortices. This behavior prevents the activation of motor cortical areas that would compete with the voluntary movement.

Interruption or dysfunction of the indirect pathway of movement results in hyperkinesia, or dyskinesias, which are, in general, diseases which lead to the production of additional involuntary muscle activity.

Dopamine receptor

Dopamine receptors are implicated in many neurological processes, including motivation, pleasure, cognition, memory, learning, and fine motor control, as well as modulation of neuroendocrine signaling. Abnormal dopamine receptor signaling and dopaminergic nerve function is implicated in several neuropsychiatric disorders.[1] Thus, dopamine receptors are common neurologic drug targets; antipsychotics are often dopamine receptor antagonists while psychostimulants are typically indirect agonists of dopamine receptors.

Dopamine receptors control neural signaling that modulates many important behaviors, such as spatial working memory.[10] Although dopamine receptors are widely distributed in the brain, different areas have different receptor types densities, presumably reflecting different functional roles.

In humans, the pulmonary artery expresses D1, D2, D4, and D5 and receptor subtypes, which may account for vasorelaxive effects of dopamine in the blood.[11] In rats, D1-like receptors are present on the smooth muscle of the blood vessels in most major organs.[12] D4 receptors have been identified in the atria of rat and human hearts.[13] Dopamine increases myocardial contractility and cardiac output, without changing heart rate, by signaling through dopamine receptors.

Dopamine (DA) is a small-molecule neurotransmitter involved in the control of both motor and emotional behavior. Despite the large number of crucial functions it performs, this chemical messenger is found in a relatively small number of brain cells. In fact, while there are a total of 10 billion total cells in the cerebral cortex alone, there are only one million dopaminergic cells in the entire brain. – via Synaptic Transmission: A Four Step Process


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