question: How is dopamine responsible for physical movement?
comment: This answer can be very complex so much detail will be lost in trying to ELI5 but the general premise holds true. For reasons unknown, certain regions in the brain are responsible for certain things. In this case, the top part of the brain ( specifically the primary motor cortex) has neurons that connect to various muscles in your legs. In order for you to move in a precise way, these neurons must fire in a specific order and at very precise time. There are many neurotransmitters that are involved, with dopamine being one. When dopamine binds to its specific receptor, a long and complex series of reactions occur which tell the neuron receiving the message to fire (to carry the message along). A single neuron communicates with hundreds to thousands of other neurons, so the message that dopamine sent gets spread very quickly to all neurons in the appropriate area. Certain Motor neurons receives the message and tell the specific muscle in your leg to contract. The order of which the neurons "get told to fire" impacts the order of which certain muscles contract, allowing you to do something such as walking smoothly. & #x200B; Your brain takes time to "figure out" which order the neurons should fire. ie. different neural pathways develop when you are a child in order to find the specific order required for walking. This is why young children learning to walk are extremely unstable and must practice in order to walk smoothly. The child's brain must "learn" which neurons should talk to which other neurons and in which order they should talk.
passages: Section::::Regulation.
   These models of the basal ganglia are thought to be relevant to the study of ADHD, Tourette syndrome, Parkinson's Disease, schizophrenia, OCD, 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.
   The function of the dopamine neurons in the "substantia nigra pars compacta" (SNc) is complex. Contrary to what was initially believed, SNc neurons do not directly stimulate movement: instead, it plays an indirect role by regulating the more direct role of the striatum, contributing to fine motor control, as has been confirmed in animal models with SNc lesions. Thus, electrical stimulation of the "substantia nigra" does not result in movement, but lack of pars compacta neurons has a large influence on movement, as evidenced by the symptoms of Parkinson's disease.
   The mesocortical pathway is primarily involved in the regulation of executive functions (e.g., attention, working memory, inhibitory control, planning, etc.), so it is particularly relevant to ADHD. The mesolimbic pathway regulates incentive salience, motivation, reinforcement learning, and fear, among other cognitive processes. 
   Regional distribution of DAT has been found in areas of the brain with established dopaminergic circuitry including: nigrostriatal, mesolimbic, and mesocortical pathways. The nuclei that make up these pathways have distinct patterns of expression. Gene expression patterns in the adult mouse show high expression in the substantia nigra pars compacta.
  
  DAT in the mesocortical pathway, labeled with radioactive antibodies, was found to be enriched in dendrites and cell bodies of neurons in the substantia nigra pars compacta and ventral tegmental area. This pattern makes sense for a protein that regulates dopamine levels in the synapse.
   In every type of animal that has been examined, dopamine has been seen to modify motor behavior. In the model organism, nematode "Caenorhabditis elegans", it reduces locomotion and increases food-exploratory movements; in flatworms it produces "screw-like" movements; in leeches it inhibits swimming and promotes crawling. Across a wide range of vertebrates, dopamine has an "activating" effect on behavior-switching and response selection, comparable to its effect in mammals.
   Loss of dopamine neurons in the SNc is one of the main pathological features of Parkinson's disease, leading to a marked reduction in dopamine function in this pathway. Depletion of neurons in this pathway lead to the symptomatic motor deficits of Parkinson's disease including tremors, rigidity, and postural imbalance.
  
  Section::::Anatomy.
  
  The following are considered part of the nigrostriatal pathway.
  
  Section::::Anatomy.:Substantia nigra pars compacta.
   The indirect pathway of the motor circuit is thought to project from the cortex, to the putamen, and to the thalamus and brainstem indirectly by passing through the external segment of the globus pallidus (GPe) then the subthalamic nucleus (STN) before looping back to the internal segment of the globus pallidus (GPi). The indirect pathway is responsible for the termination of movement. The indirect pathway inhibits unwanted movements by simultaneous increase in excitatory input to other GPi and SNr neurons. Similar to the direct pathway, the indirect pathway is regulated by striatal dopamine. D dopamine receptors inhibit transmission via the indirect pathway. D receptors inhibit striatal neurons in the indirect, inhibitory pathway. This inhibitory effect of dopamine on the indirect pathway serves the same function as its excitatory effects in the direct pathway in that it reduces basal ganglia output, leading to the disinhibition of motor neurons.
   Gross movement – such as locomotion and the movement of arms and legs – is generated in the motor cortex, divided into three parts: the primary motor cortex, found in the prefrontal gyrus and has sections dedicated to the movement of different body parts. These movements are supported and regulated by two other areas, lying anterior to the primary motor cortex: the premotor area and the supplementary motor area. The hands and mouth have a much larger area dedicated to them than other body parts, allowing finer movement; this has been visualised in a motor homunculus. Impulses generated from the motor cortex travel along the corticospinal tract along the front of the medulla and cross over (decussate) at the medullary pyramids. These then travel down the spinal cord, with most connecting to interneurons, in turn connecting to lower motor neurons within the grey matter that then transmit the impulse to move to muscles themselves. The cerebellum and basal ganglia, play a role in fine, complex and coordinated muscle movements. Connections between the cortex and the basal ganglia control muscle tone, posture and movement initiation, and are referred to as the extrapyramidal system.
   Through this pathway the basal ganglia is able to initiate voluntary movements by disinhibiting thalamic neurons that drive upper motor neurons. This process is regulated by dopamine secreted by the striatum onto the D dopamine receptor on the SNc. Dopamine excites striatal neurons in the direct pathway. Proper striatal dopamine release is integral in the suppression of the basal ganglia output, which is needed for increased activity of the thalamic neurons. This activity in thalamic nuclei is an integral component of voluntary movement.
  
  Section::::Basal ganglia circuits.:Indirect pathway.
   Section::::Muscle tone.
  
  Although muscles can be in a relaxed state, muscles have a general resting level of tension. This is termed muscle tone and is maintained by the motor neurons innervating the muscle. Its purpose is to maintain posture and assist in quicker movements, since if muscles were completely loose, then more neuronal firing would need to take place. 
   PMVc or F4 is often studied with respect to its role in the sensory guidance of movement. Neurons here are responsive to tactile stimuli, visual stimuli, and auditory stimuli. These neurons are especially sensitive to objects in the space immediately surrounding the body, in so-called peripersonal space. Electrical stimulation of these neurons causes an apparent defensive movement as if protecting the body surface. This premotor region may be part of a larger circuit for maintaining a margin of safety around the body and guiding movement with respect to nearby objects.
   Section::::Control of gait by the nervous system.:Subsection: Regulation by the Cerebellum.
  
  The cerebellum plays a major role in motor coordination. Regulation of gait by the cerebellum is referred to as “error/correction,” because the cerebellum responds to abnormalities in posture in order to coordinate proper movement. The cerebellum sends signals to the cerebral cortex and the brain stem in response to sensory signals received from the spinal cord. Efferent signals from these regions go to the spinal cord where motor neurons are activated to regulate gait.
  
  Section::::Control of gait by the nervous system.:Subsection: Regulation by the Spinal Cord.
   A subcortical loop exists within the brain linking upper motor neurons originating in the primary motor and pre-motor cortices and the brainstem, with the basal ganglia. These upper motor neurons eventually initiate movement by controlling the activity of lower motor neurons, located in the brainstem and spinal cord, and project out to innervate the muscles in the body. Upper motor neurons also modulate activity of local circuit neurons, whose synapses are a large input to these lower motor neurons, in turn affecting subsequent movement. Thus, the basal ganglia indirectly influence movement via regulation of the activity of the upper motor neurons, which ultimately determine activity of the lower motor neurons.
   Upper motor neurons release a neurotransmitter, acetylcholine, from their axon terminal knobs, which are received by nicotinic receptors of the alpha motor neurons. In turn, alpha motor neurons relay the stimulus.
  
  From there, acetylcholine is released from the axon terminal knobs of alpha motor neurons and received by postsynaptic receptors (Nicotinic acetylcholine receptors) of muscles, thereby relaying the stimulus to contract muscle fibers.
  
  Section::::Function.:Reflex arcs.
   The motor/adaptor complex is regulated by calcium ion levels. At high concentrations, calcium ions arrest mitochondrial transport by binding Miro, causing the complex to detach from the organelle. Considering that physiological factors such as activation of glutamate receptors in dendrites, action potentials in axons, and neuromodulators may elevate calcium ion levels, this regulatory mechanism likely serves to keep mitochondria in such areas to provide calcium ion buffering and active export and, thus, maintain homeostasis.
   Section::::Functions.:Cellular effects.:Storage, release, and reuptake.
   Section::::Regions of the brain involved in pre-movement.:Supplementary motor area (SMA) proper and the primary motor cortex (M1).
  
  Functions in:
  
  BULLET::::- Initiation of movement
  
  BULLET::::- Execution of movement
  
  Section::::Bereitschaftspotential.
   The spinal cord processes and interprets proprioception in a manner similar to how our visual system processes information. When a painting is viewed, the brain interprets the total visual field, as opposed to processing each individual pixel of information independently, and then derives an image. At any instant the spinal cord receives an ensemble of information from all receptors throughout the body that signals a proprioceptive “image” that represents time and space, and it computes which neurons to excite next based on the most recently perceived “images.” The importance of the CPG is not simply its ability to generate repetitive cycles, but also to receive, interpret, and predict the appropriate sequences of actions during any part of the step cycle, i.e., state dependence. The peripheral input then provides important information from which the probabilities of a given set of neurons being active at any given time can be finely tuned to a given situation during a specific phase of a step cycle. An excellent example of this is when a mechanical stimulus is applied to the dorsum of the paw of a cat. When the stimulus is applied during the swing phase, the flexor muscles of that limb are excited, and the result is enhanced flexion in order to step over the obstacle that created the stimulus. However, when the same stimulus is applied during stance, the extensors are excited. Thus, the functional connectivity between mechanoreceptors and specific interneuronal populations within the spinal cord varies according to the physiological state. Even the efficacy of the monosynaptic input from muscle spindles to the motor neuron changes readily from one part of the step cycle to another, according to whether a subject is running or walking.
   Findings have suggested that Purkinje cell dendrites release endocannabinoids that can transiently downregulate both excitatory and inhibitory synapses. The intrinsic activity mode of Purkinje cells is set and controlled by the sodium-potassium pump. This suggests that the pump might not be simply a homeostatic, "housekeeping" molecule for ionic gradients. Instead, it could be a computation element in the cerebellum and the brain. Indeed, a mutation in the - pump causes rapid onset dystonia parkinsonism; its symptoms indicate that it is a pathology of cerebellar computation. 
   Section::::Structures and molecular pathways involved.
  
  Activity-dependent plasticity of one form or another has been observed in most areas of the brain. In particular, it is thought that the reorganization of sensory and motor maps involves a variety of pathways and cellular structures related to relative activity.
   BULLET::::- Cholinergic interneurons release acetylcholine, which has a variety of important effects in the striatum. In humans, other primates, and rodents, these interneurons respond to salient environmental stimuli with stereotyped responses that are temporally aligned with the responses of dopaminergic neurons of the substantia nigra. The large aspiny cholinergic interneurons themselves are affected by dopamine through D5 dopamine receptors.
   Motor adaptation is primarily a function of the cerebellothalamic fiber pathway. The cerebellum oversees modification of routine motor programs in response to changes in the environment (e.g. walking uphill versus walking on a flat surface). It is experimentally shown that prolonged motor adaptation, such as walking over a period of weeks while wearing an ankle cast, is accompanied by long-term potentiation of cerebellothalamic synapses, thereby facilitating the influence of the cerebellum on the motor cortex.
  
  Section::::Clinical significance.
   Dopaminergic inputs from the VTA modulate the activity of GABAergic neurons within the nucleus accumbens. These neurons are activated directly or indirectly by euphoriant drugs (e.g., amphetamine, opiates, etc.) and by participating in rewarding experiences (e.g., sex, music, exercise, etc.).
   Progress in understanding the functions of the basal ganglia has been slow. The most popular hypotheses, broadly stated, propose that the basal ganglia play a central role in action selection. The action selection theory in its simplest form proposes that when a person or animal is in a situation where several behaviors are possible, activity in the basal ganglia determines which of them is executed, by releasing that response from inhibition while continuing to inhibit other motor systems that if activated would generate competing behaviors. Thus the basal ganglia, in this concept, are responsible for initiating behaviors, but not for determining the details of how they are carried out. In other words, they essentially form a decision-making system.
  