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Gitelman's syndrome (GS), also referred to as familial hypokalaemia-

hypomagnesaemia syndrome, is an autosomal recessive renal tubular disorder


characterised by hypokalaemic metabolic alkalosis, hypomagnesaemia and
hypocalciuria. It is caused by a defect of the thiazide-sensitive sodium chloride co-
transporter at the distal tubule. This condition was previously confused with Bartter
syndrome. Documentation of hypocalciuria helps to differentiate GS from Bartter
syndrome. We report a 44-year-old woman who presented with a history of seizure
disorder and periodic paralysis. On investigation, she was found to have
hypokalaemic metabolic alkalosis, hypomagnesaemia, hypocalciuria,
hypoparathyroidism, hypocalcaemia and basal ganglia calcification, consistent with
GS. The atypical features in our case, namely basal ganglia calcification and
hypocalcaemia, prompted the writing of this case report.
PMID
23112035 [Indexed for MEDLINE]

skeletal muscles. The basal ganglia refine action signals from the cortex, thereby ensuring
that an appropriate motor plan is communicated to the muscles. Unlike the pyramidal
pathway, the basal ganglia process information indirectly in a set of loops, whereby they
receive input from the cortex and return it to the cortex via the thalamus. In that way the basal
ganglia modify the timing and amount of activity that leaves the cortex and travels down the
pyramidal pathway, amplifying activity that leads to a positive outcome and suppressing
activity that leads to a deleterious outcome in a particular situation.

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Much knowledge about the role of the basal ganglia in brain function has come from the
study of disorders that affect the different nuclei. Typically, such disorders lead to difficulty
with initiating wanted movements (as generally seen in Parkinson disease) or with
suppressing unwanted movements (as seen in Huntington disease).

Anatomy And Connections


Anatomically, the basal ganglia consist of parallel complementary pathways that process
motor, limbic, sensory, and associative information. The basal ganglia of the motor circuit
include the caudate nucleus and putamen (known collectively as the dorsal striatum), the
subthalamic nucleus, the globus pallidus externus and internus, and the substantia nigra pars
reticulata and pars compacta. The basal ganglia of the limbic circuit, which processes
information about motivation and emotion, include the nucleus accumbens (ventral striatum),
ventral pallidum, and ventral tegmentum. Sensory information and associative information
(which links details about previously unrelated items) are also processed through parallel
pathways involving these nuclei, providing input to be integrated into an action plan by the
basal ganglia.
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The major input nucleus of the basal ganglia is the striatum (collectively including the dorsal
and ventral divisions), which receives information from almost all areas of the cortex. The
dorsal striatum (upper region of the striatum) receives information from areas below the
cortex (e.g., the midbrain) via the thalamus. In the motor circuit the subthalamic nucleus
serves as an input nucleus, receiving information from the cortex and thalamus and
influencing the conventional route of basal ganglia outflow from the striatum to the output
nuclei of the thalamus. The output nuclei of the basal ganglia are the globus pallidus internus
and substantia nigra pars reticulata in the motor pathway and the ventral pallidum in the
limbic pathway. Information that exits the basal ganglia goes to the thalamus, primarily the
ventroanterior and ventromedial motor thalamic nuclei for the motor pathway and the
mediodorsal thalamic nucleus for the limbic pathway, and then is sent back to the appropriate
part of the cortex.

Neurochemicals
The majority of basal ganglia nuclei have projection neurons (neurons with axons that extend
into adjacentbrain areas) that utilize the inhibitory neurotransmitter gamma-aminobutyric
acid (GABA). As a result, inhibitory signals form the basis of most communication between
nuclei in the basal ganglia. Exceptions include the excitatory glutamate-releasing projections
of the subthalamic nucleus and the dopamine-releasing projection neurons from the
substantia nigra pars compacta.
The striatum, which serves as a gateway for the regulation of signals through the basal
ganglia during the learning of actions and the selection of desirable actions, has the most-
complex signaling architecture. In addition to receiving vast external excitatory input from
the cortex and thalamus, it also contains several types of interneurons (neurons that connect
sensory and motor circuits) and some of the highest levels in the brain of the neurochemicals
dopamine and acetylcholine. Collectively, these substances modulate the way in which
excitatory inputs are processed and contribute to the final output from the striatum.

Function: Movement Generation


In order to execute purposeful movements, a small number of motor plans in the brain need
to be promoted and integrated, while others that impair or stop the execution of the desired
movement must be suppressed. Action selection is facilitated by the nature of the parallel
pathways, the number of neurons involved in the processing of information as it progresses
through the basal ganglia, and the manner in which these neurons are arranged. The input and
output nuclei generally contain the largest and smallest numbers of neurons, respectively. As
information progresses through the basal ganglia, each neuron integratesinformation that has
been transmitted from many other neurons in preceding nuclei; hence, the signal becomes
increasingly focused and specific as it passes through the basal ganglia. The process of
determining which signals are promoted occurs early in the basal ganglia circuit—at the
striatum; the neuromodulator dopamine plays a key role in signal promotion.
Parallel pathways within the basal ganglia circuits facilitate signal promotion and signal
inhibition. Neighbouring pathways carrying information about elements of the same desired
movement successively amplify the promoted signal as it progresses through the basal
ganglia. More often, however, neighbouring pathways act to reduce unwanted signals,
ensuring that an accurate, precise, and optimized action plan is developed. In the absence of
action selection, all motor plans are promoted and many muscles around the body are
activated, leading to a failure to execute desired actions.

Cell Physiology
The brain encodes and transmits information between areas in the form of electrical impulses
called action potentials. The processing and relaying of information in the basal ganglia are
complex, because the majority of neurons release GABA when they fire action potentials,
generally inhibiting the activity of cells in the target areas. Therefore, a basic operating
principle of information progression through the basal ganglia is the removal of the net
inhibition imposed by output nuclei onto target areas in the thalamus and cortex, a process
known as disinhibition. The final behavioral outcome depends on the timing and
spatial dynamics of firing events in single neurons and groups of neurons (local networks) as
well as across parallel pathways (large networks).
The importance of the basal ganglia in generating movements is evident from the rate and
pattern of action potentials fired in neurons during the preparation for and execution of
movements. The majority of neurons alter their activity after the movement has started,
which supports the idea that the basal ganglia are able to fine-tune movements. Some neurons
in the basal ganglia, however, have precise roles in learning and the cueing of movement. For
instance, neurons in the striatum that manufacture acetylcholine show a dramatic pause in
their firing when a sensory signal (e.g., a flash of light or unusual sound) is associated with a
meaningful action (e.g., sitting or running). Such signals conversely cause dopamine neurons
in the substantia nigra pars compacta and ventral tegmental area to fire faster for a few
hundredths of a second, thereby releasing pulses of dopamine into the striatum. Together, the
timing of acetylcholine and dopamine release teaches the striatum which signals to pay
attention to (e.g., signals that lead to a rewarding outcome) and allows it to learn which action
recently performed led to the appearance of these signals. This results in the reinforcement of
specific pathways through the striatum, ensuring that desirable actions reoccur more
frequently in the future. Through this process, for example, a dog learns that a whistle from
its owner will lead to a treat after it performs the requested action of sitting.
Reinforcement occurs at the cellular level by strengthening synaptic inputs from the cortex
onto cells in the striatum through a mechanism called synaptic plasticity. Dopamine plays a
key role in this process and is essential for both strengthening synaptic inputs as well as
weakening synaptic inputs that code for unwanted and undesirable motor plans. Thus,
dopamine neurons act as gatekeepers, controlling which messages progress from the striatum
to other basal ganglia nuclei during the action-selection process. Furthermore, through the
activity of dopamine neurons, the basal ganglia also provide the motivation to perform
behaviours that are required to explore, interact with, and learn from one’s environment.

Basal Ganglia Dysfunction


Basal ganglia dysfunction leads to movement disorders and changes in behaviour. In some
cases, degeneration of a specific population of neurons is the underlying pathology of
neurological diseases. For example, a loss of more than 60 percent of dopamine neurons leads
to Parkinson disease, whereas loss of a smaller percentage of projection neurons in the
striatum underlies the pathology of Huntington disease. Although both Parkinson and
Huntington diseases are associated with movement disorders, the former is generally
characterized by hypokinesia (abnormally reduced range of movement) and the latter by
hyperkinesia (abnormally increased movement). Thus, symptoms are determined by both the
population of cells that is lost and the role that the cells played in action selection. In both
diseases, habitual (automatic) movements are more severely affected than goal-directed
movements (responding to cues). Some rehabilitation aids help convert habitual movements,
such as walking, into a goal-directed task by providing patients with a cue (e.g., a visual red
line projected from a walking cane that the patient needs to step over). The loss of a single
neuronal population has widespread consequences, because it changes the firing rate and
pattern throughout the basal ganglia parallel pathways and alters the number and form of
synaptic connections between neurons.

Basal ganglia dysfunction also can be accompanied by a nonmotor disorder. For


example, cognitivefunction (memory and reasoning) and motivation are impaired in both
Parkinson and Huntington disease. Alterations in dopamine function are also implicated
in attention deficit-hyperactivity disorder (ADHD), schizophrenia, Tourette syndrome,
and obsessive-compulsive disorderand following prolonged exposure to drugs and alcohol in
substance abuse. In nonmotor involvement, the cause of the dysfunction is complex and not
dependent on the loss of one neuronal population. Progress in the understanding of basal
ganglia function and dysfunction could lead to the development of novel therapies for both
motor and nonmotor disorders, particularly those associated with abnormal neurochemical
activity in the basal ganglia.
Louise C. Parr-BrownlieJohn N.J. Reynolds

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MORE ABOUT Basal ganglia

6 REFERENCES FOUND IN BRITANNICA ARTICLES

Assorted References

 major reference
 In human nervous system: Basal ganglia
 In human nervous system: Basal ganglia
 Huntington disease
 In Huntington disease
 neurological disease
 In nervous system disease: Basal ganglia and thalamus
 In nervous system disease: The basal ganglia
 vertebrate nervous systems
 In nervous system: Dominance of the cerebrum

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