Basal Ganglia- Wilson Flashcards
What is the function of the basal ganglia?
involved in motor gating
- selecting the appropriate motor function to be executed
- inhibiting other possible choices (suppressing unwanted activity)
The basal ganglia is important in initiating and stopping what kind of motor function?
voluntary
What is meant by ‘gating’, the function of the basal ganglia?
- the brain has millions of motor programs from which to choose
- there has to be a method for figuring out which function of the body should be performed and which ones should not at a given time
In order to execute a motor program what are the steps needed to be taken by the nervous system AKA the basal ganglia/ gate keeper?
- select the program
- stop the current program
- load the program
- while inhibiting the execution of other programs
What occurs when there is lesion to the basal ganglia?
hemiballism: very ballistic movements that are expressed
these violent movements are controlled by neuroleptic (drugs) which are not selective to the diseased side of basal ganglia thus you develop a parkinson’s type tremor and bradykinesia
there is probably a vascular event affecting the function of the basal ganglia (subthalamus)
Diseases of the basal ganglia result in hypokinetic and hyperkinetic disorders. What are examples of hypokinetic disorders and what are its characteristics?
Parkinson’s disease
- bradykinesia (akinesia)
- rigidity
Diseases of the basal ganglia result in hypokinetic and hyperkinetic disorders. What are examples of hyperkinetic disorders and what are its characteristics?
Huntington’s chorea
- dyskinesia (dystonia)
- hypotonia
Describe the circuits in the basal ganglia.
the circuits in the BG are antagonist
some turn on some turn off
as long as these circuits are balanced we get normal movements like you and I and no unwanted movement
Basal ganglia, caudate nucleus, and putamen have very high levels of acetylcholine relative to dopamine in what type of disease of the basal ganglia? What pathway is overactive?
hypokinetic (Parkinson’s disease)
the indirect pathway is the dominant way through which information is streaming through the basal ganglia; direct pathway is suppressed
Basal ganglia, caudate nucleus, and putamen have very high levels of dopamine compared to acetylcholine in what type of disease of the basal ganglia? What pathway is overactive?
hyperkinetic (dyskinesia)
taking a lot of cocaine and hyperkinetic diseases amphetamines can artificially produce this type of imbalance
-the direct pathway is overactive; could be due to diseases suppressing the indirect pathways or drugs like cocaine causing direct pathway to be overactive
What is the topographic definition of the basal ganglia?
part of the deep cerebral nuclei embedded in white matter of the cerebral cortex
the subcortical nuclei of the basal ganglia includes:
- caudate nuclei (extends throughout all the layers of the cerebral cortex); runs in the lateral wall of the lateral ventricle; head near the frontal lobe, body near the parietal/occipital region, and tail in the temporal lobe
- putamen
- globus pallidus
- amygdala: important role in the limbic system; located at the tail of the caudate nucleus in temporal lobe region
Which nuclei in the basal ganglia is not discussed as functionally part of the basal ganglia?
amygdala (part of the limbic system)
Where is the caudate nucleus found?
in the lateral wall of the lateral ventricle OR medial to the anterior limb of the internal capsule
Where is the lenticular/lentiform nucleus found?
on the lateral side of both the anterior and posterior limbs of the internal capsule
Where is the putamen located?
is the lateral portion of the lenticular nucleus
looks just like the caudate nucleus and they both together are often called the striatum
Where is globus pallidus located?
medial to putamen in the lenticular/lentiform nucleus
What does the lenticular/lentiform nucleus consist of?
- putamen- most lateral
- globus pallidus (external segment)
- globus pallidus (internal segment)-most medial
What structures are associated with the functional definition of basal ganglia?
1) Striatum:
-caudate nucleus
-putamen
just separated by the internal capsule
2) Globus Pallidus:
- internal segment
- external segment
3) Substantia Nigra: dark substance of the brain (filled with neuromelanin which are waste products); gets darker as you get older and older
- pars compacta: compact cells filled with neuromelanin
- pars reticulata: few neurons
4) Subthalamus
Where is the substantia nigra located?
in the midbrain ventral to the crus cerebri
What is the cerebral peduncle made up of?
- substantia nigra
- crus cerebri
What is the difference between the pars compacta and pars reticulata of the substantia nigra?
pars compacta: dense with cells that used NT dopamine; they will stain for tyrosine hydroxylase
pars reticulata: sparse area btw crus cerebri and pars compacta; mostly dendrites and cells which are large and GABAergic (inhibitory); similar to globus pallidus
Where is the subthalamus located?
just underneath the thalamus
What separates the globus pallidus internal segment and the substantia nigra pars reticulata?
the internal capsule
What are the input nuclei of the functional basal ganglia? Which nuclei receive inputs for the basal ganglia?
- caudate nucleus
- putamen
AKA the striatum
What are the output nuclei of the functional basal ganglia? Which nuclei send outputs from the basal ganglia?
- globus pallidus (internal segment)
- substantia nigra (pars reticulata)
Histologically the globus pallidus internal segment and substantia nigra pars reticulata look identical.
FACTS
Describe the input/output organization of the basal ganglia.
- Descending motor information goes from the cerebral cortex
- to the input nuclei of the basal ganglia
- to the output nuclei of basal ganglia then to the VA/VL(central motor relay nuclei of the thalamus) which would then send information
- to the motor areas of cortex (motor and premotor cortex AKA area 4 and 6 respectively)
this information determines which movements will be executed and those that will not be executed
all areas are sending motor requests to the basal ganglia and its processes through this block like circuits
The neuronal activity of which component of the direct pathway of the basal ganglia circuit will determine movement?
thalamus
neurons start to spike at a faster rate (increased thalamic activity) –> movement will occur
decreased neuronal activity of the thalamus–> lack of movement
What is prove that the caudate nucleus and putamen are really a singular structure?
rodents lack an internal capsule, therefore, the putamen and caudate are singular structure: the (neo)striatum
in mammals with an internal capsule, the caudate (medially) and putamen (laterally) will still fuse rostrally
The striatum has a mosaic organization. Explain.
when the human striatum is stained histochemically for acetylcholinesterase at least 2 compartments can be identified: patch (dark) and matrix (white)
The patch/matrix can be distinguished:
- anatomically
- biochemically
- pharmacologically
- behaviorally
Where does the striatum receive input from?
- (essentially) all areas of cortex (whether visual or auditory)
a. glutaminergic
b. excitatory - substantia nigra
a. pars compacta
b. dopaminergic - thalamus, intralaminar nuclei (central median nucleus and parafascicular nucleus)
The largest part of the striatum receives input from the motor areas of the cortex. What is this portion called?
caudate nuclei head
the motor input of the striatum is the densest and heaviest
The loss of what input to the basal ganglia is thought to cause Parkinson’s disease?
dopaminergic input
Which part of the striatum receives information from primarily motor, premotor, and somatosensory cortices?
putamen
Which part of the striatum receives information from the associational cortex and frontal eye fields?
caudate nucleus
What type of cells make up 90% of the striatal cells?
medium spiny neurons
- medium cell body size
- dendrites are long and studded with spines through which cortical information will go
The output of the striatum is excitatory or inhibitory? Where do they project to? Explain.
inhibitory
- the medium spiny neurons (make up 90% of striatal cells) are projection cells which are GABAergic (inhibitory)
- they project to the internal segment of the globus pallidus and the pars reticulata of the substantia nigra
T/F. Medium spiny neurons are of high spontaneous activity.
False- they are of LOW spontaneous (no stimulus) activity; quiet
What are the 2 parallel circuits through the basal ganglia?
- direct pathway to the internal segment of globus pallidus and pars reticulata of substantia nigra
- indirect pathway
What is the difference between the direct and indirect pathway?
direct pathway:
- increase in cortical through-put thus promotes movements
- lesions to the pathway produce HYPOkinetic symptoms
indirect pathway:
- decreases cortical through-put thus stops movements
- lesions produce HYPERkinetic symptoms
*if the site of lesion is at the input stage
All outputs from the cerebral cortex are excitatory or inhibitory?
excitatory
-they use either glu or asp
Like the striatum, the internal capsule divides the output of the basal ganglia into what two nuclei?
globus pallidus, internal segment
substantia nigra, pars reticulata
cytologically GPi and SNr are identical
What type of cells make up the output nuclei of the basal ganglia? What are their characteristics?
large aspiny neurons
- have relatively high rate of spontaneous (no stimulus) activity
- are GABAergic (inhibitory)
- are projection neurons
so globus pallidus, internal segment and substantia nigra pars reticulata are tonically inhibitory
Where do the output nuclei of the basal ganglia project to?
ventral anterior and ventral lateral nuclei of the thalamus
via the lenticular fasciculus (H2) and
ansa lenticularis
The thalamocortical neurons projecting to areas 4 and 6 are excitatory or inhibitory?
excitatory
How does the thalamus neuronal activity increase when the basal ganglia is active?
through disinhibition
- striatum is normally quiet but if you give it an excitatory stimulus it will inhibit the globus pallidus which is tonically inhibitory
- the inhibition of globus pallidus on the thalamus will be removed and thus activity of the thalamus will increase and relay up to the motor cortex causing movement
Excitatory cortical input into the striatum results in ________of thalamic cells.
disinhibition
as far as the brain is concerned the baseline is quiet because globus pallidus is tonically inhibitory and thus thalamic neuronal activity is low (no activity)
At rest, describe the neuronal activity of the caudate nucleus, globus pallidus, and thalamus.
- caudate nucleus: quiet (low spontaneous activity)
- globus pallidus (tonically inhibitory-high spontaneous activity)
- thalamus: quiet (as it is inhibited by globus pallidus)
In Huntington’s disease, what degenerates causing an enlargement of the lateral ventricle? What are symptoms of Huntington’s disease?
the striatum (remember caudate nucleus is lateral to the lateral of the lateral ventricle)
- a lot of movement of the hands and wrist
- a hyperactive condition???????
What is chorea and athetosis?
chorea is more associated with the striatum
athetosis is:
- irregular, slow, sustained movements
- more associated with the putamen
- slow, writhing, continuous, wormlike movements of the distal extremities
- difficult to differentiate from chorea
What is ballism?
- very violent movements more involved in the shoulders, proximal, and distal limbs
- wide, massive movements predominantly proximal and hemilateral
(the lady sitting in chair with uncontrollable movements)
Ballism is often due to vascular lesion to what?
vascular lesions to the subthalamus
What are the connections of the subthalamus to the basal ganglia?
forms the central part of the indirect pathway through the basal ganglia
The output of the subthalamus is excitatory or inhibitory?
excitatory
What is the indirect pathway of the basal ganglia?
cerebral cortex sends excitatory information to the striatum which send inhibitory information to the globus pallidus external segment which will send inhibitory efferents to the subthalamus
the subthalamus sends excitatory efferents to globus pallidus internal segment and substantia nigra pars reticulata
The output of the direct and indirect pathways are expressed through what neurons projecting to the (VA/VL) to cortical area 4 and 6?
thalamocortical neurons
Pathological___________ in firing of TC neurons result in hyperkinetic symptoms.
Pathological___________ in the firing of TC neurons result in hypokinetic symptoms.
increases
decreases
Parkinson’s disease is a hyper or hypokinetic disorder?
hypokinetic
What is consistently found in the brains of Parkinsonians?
lesion of the substantia nigra, pars compacta, and depletion of striatal dopamine
loss of staining when staining for tyrosine hydroxylase
What neurotransmitter from the substantia nigra pars compacta modulates neural activity in the striatum?
dopamine
Is dopamine inhibitory or excitatory in the direct and indirect pathway?
dopamine (D1 receptors) is excitatory in the direct pathway
dopamine (D2 receptors) is inhibitory in the indirect pathway
What is the result of a lesion in the dopaminergic input in the direct and indirect pathway?
hypokinesia- decrease in thalamic neuronal activity
Dopaminergic input into either or both basal ganglia pathways affects the activity of thalamocortical neurons in what way?
increase in movements (hyperkinetic symptoms)
What occurs when there is balance between the direct and indirect pathways of the basal ganglia?
normal movement
What occurs when there is imbalance between the direct and indirect pathways of the basal ganglia?
dyskinesias
What is the major neurotransmitter in the striatum?
acetylcholine
Giving patients D1 and D2 antagonist will result in hyper or hypokinetic movements?
hypokinetic movements
Giving patients D1 and D2 agonist will result in hyper or hypokinetic movements?
hyperkinetic movements
What are the 3 major symptoms of Parkinson’s disease?
- resting tremor
- rigidity: stiffness about a joint either flexing or extending; velocity independent
- bradykinesia–>akinesia: reduced amount of movement to no movement
What are the 4 basic strategies for treating Parkinson’s disease?
- L-dopa (replacement) therapy: if cells in the substantia nigra are low you can give them extra precursors L-dopa to produce dopamine
- stereotaxic lesions of the internal segment of the globus pallidus (GPi, pallidotomy): can restore part of the brain that is inactive
- deep brain stimulation of GPi or subthalamus (in clinical trial stage) : through electrical stimulation can restore the imbalance
- brain transplant (no comment)
What is the gold standard for treating Parkinson’s disease? What does this treatment entail?
L-dopa therapy
- does not stop the disease process
- is not, therefore, an effective strategy in more advanced stages of Parkinson’s disease (When too few cells are remaining)
- does not expose the brain to a continuous dose of dopamine when administered oral doses
- produces, therefore on/off side effects (chorea)
Describe stereotaxic surgery.
-if you put the brain in a particular orientation you can identify the subthalamus by a set of coordinates
When the head is held in the stereotaxic plan, the brain can be mapped by a standard set of stereotaxic coordinates.
Every structure of the brain has it own unique set of stereotaxic coordinates.
Using stereotaxic coordinates, an electrode can be position in the globus pallidus which then can be electrolytically lesioned.
-there is variability and so may not hit the exact spot
What are disadvantages of electrolytic lesions?
- difficulty in placing the electrode in the precise location for lesion
- difficulty in determining and controlling the optimal size of the lesion
- impossibility of adjusting the lesion size based on the patient’s response
- complication from unexpected hemorrhage and/or infection
What is deep stimulation?
- currently is being tested in clinical trials
- avoids many of the limitations of lesion
- most importantly, stimulation strength can be constantly adjusted to optimize therapeutic action as the disease progresses
gives greater flexibility
Over 100 neuroactive substances have been identified in the striatum.
The basal ganglia may be involved in reward-based motor learning.
FACTS
cerebellum is involved in error-based motor learning
