Greg Detre
Thursday, 22 June, 2000
Prof. Rolls B&B VIII
The basal ganglia is made up of different collections of neurons within the cerebral hemispheres that are involved in regulating movement. Two of the various structures that make up the basal ganglia are the ventral striatum and the ventral pallidum. These neurons are "thought to be involved in the control of complex patterns of motor activity, such as skilled movements." (1)
There are two main ways in which the basal ganglia play a role in motor activity. First, some parts of the basal ganglia regulate "how rapidly a movement is to be performed and the magnitude of the movement." (1) Second, some structures of this area of the brain "are thought to influence cognitive aspects of motor control, helping to plan the sequence of tasks needed for purposeful activity." (1)
Malfunctions in processes such as those mentioned above help one to understand the important role of this area of the brain. Disease symptoms that affect this area of the brain include abnormal movements, known as dyskinesias, "such as chorea (jerky movements), athetosis (writhing movements), and tremors (rhythmic movements)," which all can result from abnormalities in how the basal ganglia send messages concerning the rapidity and magnitude of the movement. (1)
Making up part of the basal forebrain, the ventral striatum receives input important to the regulation of emotion from other limbic areas. This structure has been referred to as "one of the crossroads where emotional and motoric information can influence each other." (3) After the ventral striatum receives information from other limbic areas, it relays those messages to the ventral pallidum. In addition, as also being part of the basal ganglia, both the ventral striatum and pallidum may play a role in the regulation of movement, including the control of complex motor activity and the cognitive aspects of motor control.
The ventral pallidum is one of the structures of the basal forebrain. It plays a role in regulating human emotionality by acting as a receiver of important input sent to it from the ventral striatum. Also, as being part of the basal ganglia, both the ventral striatum and pallidum may play a role in the regulation of movement, including the control of complex motor activity and the cognitive aspects of motor control.
"Lower Motor Neuron" (LMN) =
final common pathway. All motor systems must act on the LMN in order to
illicit a motor response or behavior. If all of the motor neurons to a muscle
(OR all the axons) are damaged -> there is NO movement of the muscle
(voluntary or otherwise). There is NO tone, there are NO reflexes in that
muscle. It does not matter what state the UMNs are in - if the LMNs to the
muscle don't work, that's it! (i.e., you cannot have UMN disease in a muscle
that has complete LMN disease)
LMNs vs interneurons.
Review - one more time - "lower motor
neuron disease" = lesions of LMNs or their axons.
The symptoms include:
flaccid paralysis/paresis - In the case of paralysis, the muscle usually
innervated by the damaged LMNs is totally limp or flaccid. There is absolutely no
neural activity going out to the muscle.
hypotonia - In the case of paralysis, there would be no tone
left in the muscle - it is limp!. In the case of paresis there would be
decreased muscle tone.
hyporeflexia or areflexia - In the case of paralysis, there
would be no reflex left at all because there is NO neural input to the muscle
AT ALL. In the case of paresis, the reflexes would be decreased.
fibrillations or fasciculations - This occurs during the
degeneration/atrophy process. As the LMN dies, neurotransmitter is
spontaneously released from dying nerve terminals leading to fibrillations
(individual muscle fibers twitch - detectable electrophysiologically, but not
visible to the eye). In addition, as individual & small groups of axons
die, the membrane(s) become depolarized and spontaneous action potentials
proceed from the point of depolarization. This leads to the release of
neurotransmitter in individual or small groups of motor units causing
fasciculations which are visible to the naked eye.
Review - one more time - "upper motor
neuron disease" = lesions of UMNs or their axons.
The symptoms include:
spastic paralysis/paresis - In the case of paralysis, the muscle usually
innervated by the damaged LMNs is totally limp or flaccid. There is absolutely no
neural activity going out to the muscle.
hypertonia - In the case of paralysis, there would be no tone
left in the muscle - it is limp!. In the case of paresis there would be
decreased muscle tone.
hyperreflexia - In the case of paralysis, there would be no reflex
left at all because there is NO neural input to the muscle AT ALL. In the case
of paresis, the reflexes would be decreased.
Pathological reflexes - e.g. Babinski sign.
Innervation of trapezius &
sternocleidomastoid - contra from
corticospinals, ipsi from cortico"bulbars". Damage to
either set of UMN's only causes weakness (vs paralysis).
We're going to go ahead and get started on
the Basal Ganglia today. We'll start with the terminology and the basic wiring
of the various structures. Then on Monday we'll go into some detail of the
functions. Bottom line: basal ganglia are going to alter the activity of UMNs
in the 1� motor cortex, by way of the thalamus.
Basal Ganglia = Caudate + Putamen + Globus Pallidus
Misnomer - groups of cell bodies within the
CNS should be called nuclei (hence these nuclei are sometimes refered to as
deep nuclei within the cerebrum) but most commonly they are referred to as the
basal ganglia.
Anatomically: Putamen + Globus Pallidus
are immediately next to each other and early anatomists thought they looked
like a lens - so they named them together as the lenticular nucleus
Functionally:
Caudate + Putamen are related, input into the basal ganglia enters
either the caudate or the putamen. Together, these two nuclei are often
referred to as the striatum (or neostriatum). Developmentally these
nuclei are of the same origin. Rostrally, they are still fused, but caudally,
the internal capsule dives through and divides them (caudate medial to IC and
putamen lateral to IC).
Globus Pallidus = output structure of the basal ganglia.
Other connected structures: subthalamus,
substantia nigra, and certain thalamic nuclei
Named fiber tracts: ansa lenticularis,
lenticular fasciculus, thalamic fasciculus
Curcuit diagram: draw in connections on
diagram in lab manual.
In lab tomorrow: Redraw these curcuits
Blood Supply - Review: (use sketches)
branches of ACA => head of caudate
lenticulostriate arteries => body of
caudate, putamen & globus pallidus
branches of MCA => tail of caudate
branches of PCA => thalamus, subthalamus, substantia nigra
Basal Ganglia = Caudate + Putamen + Globus Pallidus
Anatomically: Putamen + Globus Pallidus
= lenticular nucleus
Functionally:
Caudate + Putamen = striatum (or neostriatum), input structure of the
basal ganglia
Globus Pallidus = output structure of the basal ganglia (Although, as
seen on the wiring diagram we've given, you there is some output from the
substantia nigra too. But this is a minor component).
Other connected structures: subthalamus,
substantia nigra, and thalamic nuclei: CM, intralaminar nuclei, VA and VL.
Named fiber tracts: ansa lenticularis, lenticular
fasciculus, thalamic fasciculus
Main points:
1) Lesions: disruption of movements & may
also cause significant cognitive, perceptual and mentation deficits. We'll
emphasize the movement disorders.
2) Circuit diagram we did last week is
typical (albeit very simplified) pathway from cortex through the basal ganglia,
back to cortex. Basal ganglia modify cortical activity
3) Main function is disinhibition. There are
many inhibitory synapses in series. Remember - inhibition of an inhibitory
neuron results in greater levels of activity for that's neurons targets ( - x -
= +)!
4) Divided into a direct and indirect
pathway. These pathways have opposite actions on their target nuclei.
Bottom line, stimulation of the direct pathway increases the activity of the
thalamus while stimulation of the indirect pathway decreases the activity of
the thalamus. Balance between these pathways is all important and determines
the amount of inhibitory outflow from the basal ganglia.
Bottom line = functions as a series of
parallel curcuits from cerebral cortex, through the basal ganglia, to thalamus
and back to cerebral cortex.
Keep in mind, there are lots of modulatory
connections we are not going to go into in detail - e.g., intrastriatal
connections (using the excitatory neurotransmitter ACh) such that the
direct & indirect pathways can modulate one another, connections between
the internal and external globus pallidus, connections between pars compacta
and pars reticulata (see below) of substantia nigra, etc.
Now let's add in the sign of each synaptic
connection.
Striatum - not much spontaneous activity, input from thalamus & cortex
is mostly excitatory. Input from substantia nigra is both excitatory and
inhibitory depending on the type of receptors on the striatal neurons. Output
is predominantly GABAergic, therefore inhibitory to globus pallidus and
substantia nigra (pars reticulata - see below)
Globus Pallidus - high rates of spontaneous activity, output cells
are mostly GABAergic, therefore globus pallidus tonically inhibits its
targets! Thus internal (or medial) segment tonically inhibits VA, VL &
CM of thalamus. External (or lateral) segment tonically inhibits the
subthalamus.
Subthalamus - normally inactive because of inhibition from
globus pallidus. If this inhibition is removed, then these cells exhibit a high
level of activity. Output is glutamatergic (excitatory) to the internal globus
pallidus.
Substantia Nigra - two regions - 1) pars reticulata, cell poor
zone, lots of GABAergic neurons - 2) pars compacta, cell rich zone, many
neurons containing dopamine and melanin pigments (melanin gives the substantia
nigra its dark appearance).
Pars reticulata is the part that acts much like the internal segment
of the globus pallidus: it is part of the direct pathway, is tonically active,
and inhibits (GABAergic) VA/VL/CM.
Pars compacta is the part important in Parkinson's disease.
Dopaminergic neurons here project back to the striatum. These projections can
have excitatory or inhibitory effects depending on the type of receptor on the
striatal neuron. Turns out, these projections excite the direct pathway and
inhibit the indirect pathway => both decreasing thalamic activity (follow
the circuits and know why!!!).
Activity along the direct pathway -> disinhibition
of the thalamus and thus increased thalamic activity
Activity along the indirect pathway -> disinhibition
of the subthalamus -> increased stimulation to internal segment of
globus pallidus -> increased inhibition of the thalamus.
Lesions of the basal ganglia ->
significant changes in motor behavior. Can be hypokinetic (decreased amount of
motor activity) or hyperkinetic (increased amount of motor activity).
Hypokinetic:
akinesia = impairment of the initiation of movement
bradykinesia = reduced velocity or amplitude of movement.
Both seen in Parkinson's disease -
loss of dopaminergic neurons in the pars compacta of substantia nigra. Since
substantia nigra is the major source of DA sent to the striatum, this disease
results in an inbalance of the DA/ACh ratio in the striatum with ACh being now
relatively too high and DA relatively too low. Bottom line: activity of direct
pathway is reduced while activity of the indirect pathway is increased (thus
gross inbalance of direct & indirect) -> both lead to increased
inhibition of the thalamus. In lab tomorrow, go over these pathways and
understand this.
Symptoms: difficulty initiating movements & stopping them
once started, tremor (at rest), rigidity (hypertonia in flexors &
extensors), loss of "associated movements" (e.g., swinging arms while
walking). Loss of dopamine in the putamen is greatest on side contralateral to
the more affected side.
Treatment: administration of L-Dopa which can cross the
blood-brain barrier and be converted to dopamine. Over treatment can induce
choreiform movements (see below).
Hyperkinetic:
ballism
= uncontrolled flinging of upper or lower limb.
choreiform movements = brisk, graceful involuntary movements of
distal extremities and face. Well coordinated, often referred to as
"dance-like".
athetoid movements = continuous writhing of limbs (esp. hands), face and
tongue.
Huntington's disease - results from loss of both GABA and ACh neurons in
the striatum. Now the DA/ACh ratio in the striatum is too high - postulated
that the indirect pathway is more effected than the direct pathway. Thus too
much disinhibition of the thalamus and too much thalmic activity ->
hyperkinetic disorder
Symptoms: choreiform/athetoid movements and
dementia. Progressive. Movement disorders begin in distal extremities but ends
up affecting the entire body.
Hemiballism - lesion of the subthalamus results in ballism
contralateral to the lesion.
Diseases:
Schizophrenia - increase in the number and sensitivity of D2
receptors on stiatal neurons (these cells receive dopaminergic input from the
ventral tegmental area). Treated with drugs that block these D2 receptors.
In lab tomorrow: Redraw these curcuits & understand disinhibition
Blood Supply - Review: (use sketches)
branches of ACA => head of caudate
lenticulostriate arteries => body of
caudate, putamen & globus pallidus
branches of MCA => tail of caudate
branches of PCA => thalamus & subthalamus