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MSP Neuroscience
Problem Set #4
1.a. Name the subdivisions of the diencephalon from dorsal to ventral.
1. Epithalamus 2. Thalamus 3. Subthalamus 4. Hypothalamus
b. Name the principal thalamic nuclei and the functional/anatomical
pathway with which they are in involved.
ventrobasal (vpl/vpm): somatosensory, lateral geniculate: visual, medial geniculate: auditory,
anterior nuclei: related to the hippocampus, ventralis lateralis: relay on the cerebellar-cerebral
pathway, ventralis anterior and centromedian: related to basal ganglia, intralaminar: wakefulness
and gaze orientation.
c. Describe the general circuitry of projections within the Thalamus as well as those which
project from the Thalamus to structures in other areas of the CNS.
Except for nucleus reticularis, all thalamic nuclei project upwards and thus have connections
with the cerebral cortex and basal ganglia. There are no significant descending projections and
there is little action between thalamic nuclei. The exception to this, is the nucleus reticularis. It
surrounds the Thalamus and receives projections from both thalamic nuclei and cerebral cortex
and then projects back to thalamic nuclei (possibly acting as filter between cortex and thalamic
nuclei). Individual thalamic nuclei connect in general with a particular cortical area, and these
connections are reciprocal.
2.a. Describe the major functions of the Basal Ganglia.
The basal ganglia participate in the initiation and control of movement but do not have direct
access to the spinal cord and its motor neurons. May play important roles in motor planning and
programming. Also, may contribute to cognitive aspects of behavior (organizing goal-directed
behavior).
b. Basal ganglia circuitry is generally defined as consisting of the
Globus Pallidus (external and internal segments),
Subthalamic nucleus, and Substantia nigra (pars compacta).
Caudate/Putamen,
Identify the primary neurotransmitters that arise from each neuroanatomical
region and identify the output destination. Also identify important input to
each region.
See Figure 42-5 on page 6 of the Basal ganglia notes.
c. Give the general signs and symptoms observed with disorders of the basal ganglia.
Disorders of the basal ganglia are characterized by changes in muscle tone, abnormal,
involuntary movements (dyskinesis), and difficulties in the initiation or control of movements,
but no paralysis.
3.a. Compare and contrast the functional significance of the direct pathway through the
basal ganglia with the indirect pathway through the basal ganglia.
Activity in the direct pathway from the striatum to the output nuclei of the basal ganglia creates
a disinhibitory system. The decreased activity of the output nuclei allows increased activity of
the thalamocortical neurons, possibly facilitating movement due to increased excitation of
premotor and supplementary motor areas of the cortex.
Activation of the indirect pathway from the striatum through the subthalamic nucleus leads to
decreased activity of the thalamocortical neurons and thus may reduce movement due to
decreased excitation of the supplementary and premotor areas of the cortex.
b. Give a reasonable explanation for the co-existence of these two pathways.
These two pathways may counterbalance each other and thus help to contribute to the
maintenance of normal levels of movement and muscle tone within the body.
4. A patient comes into your office complaining of abnormal sensations and motor
functioning in his limbs. Upon examination you find that he has deficits involving pain,
temperature, vibration, and proprioception in his left arm and leg. In these same limbs
the patient is experiencing spasticity. Upon examination also reveals, that the patient has
a paralysis of the lower half of his face and the development of the Babinski sign, both on
the left side as well.
a. Where is the patient’s lesion located (be specific)?
The lesion is located in the posterior limb of his right internal capsule.
b. Give an explanation of this patients physical manifestations based on the neuronal
circuitry which may have been involved.
Coticospinal fibers of the pyramidal tract, corticobulber fibers and other motor pathways
descending to the spinal cord may have been affected. Thalamocortical somatosensory fibers
(dorsal column-medial lemniscus, anterolateral pathways) ascending in the internal capsule to
appropriate cortical areas may also have been affected. All of the pathways are related to the
opposite side of the body due to crossing of the pathways during their ascent or descent to their
specific destination.(*Somatosensory and visual symptoms may also be present depending on the
extent of the lesion.)
c. What type of pathological event could have caused a lesion affecting this area, in
which there exists, such a broad distribution of neuronal fibers?
A cerebral vascular accident within the posterior limb of the internal capsule could bring about
an ischemic infarct thus leading to the disruption of multiple neuronal tracts and the observed
symptoms. More specifically, an occlusion involving the lenticulostriate arteries could bring
about an infarct of this type.
5. Most antipsychotic drugs are targeted to lower dopamine activity in the
brain, particularly the ventral tegmental area, and act as dopamine receptor
blockers. These neuroleptic drugs are very effective in alleviating the
symptoms of psychoses, but due to the wide distribution throughout the brain
of dopamine activity many side effects are exhibited in patients treated
with dopamine receptor blockers. These adverse reactions, particularly in
high potency antipsychotic drugs, can present with drug-induced symptoms of
bradykinesia, tremor, and rigidity.
Propose a likely mechanism by which high potency dopamine receptor blockers
can illicit these symptoms. What disease do these symptoms mimic? What major
pathological change is exhibited in this disease? Describe, in detail, the
(direct) pathway involved in causing these symptoms. Include all anatomic
regions, synapses, and neurotransmitters involved.
The hallmark symptoms of Parkinson’s Disease are bradykinesia, tremor, and
rigidity. The most likely mechanism by which these parkinsonian symptoms can
arise are by blocking the release of dopamine by neurons of the Substantia
nigra, pars compacta, onto the dopamine receptors located in the striatum
(caudate/putamen); effectively disturbing the nigrostriatal pathway. By
effectively blocking this neurotransmitter’s activity, these drugs mimic
Parkinson’s disease. Parkinson’s disease is the loss of dopaminergic neurons
in the substantia nigra, pars compacta. These dopaminergic neurons synapse
upon GABAergic neurons in the striatum (caudate/putamen). The lack of
dopamine stimulation upon these neurons causes substantially decreased
activity by the inhibitory GABAergic neurons in the direct path. These GABAergic neurons
synapse upon another set of inhibitory GABAergic neurons located in the
internal segment of the Globus pallidus. The decreased GABAergic activity in
the striatum causes decreased inhibitory influences upon the inhibitory GABA
neurons in the Globus pallidus (internal segment). This is essentially a
lack of disinhibition, in other words the Globus Pallidus, internal segment,
GABAergic neurons are secreting GABA at a higher rate. These hyperactive
GABAergic neurons are sustaining a high degree of inhibition on thalamic
neurons that project to the cortex. Thus the removal of dopamine influences
in the basal ganglia could lead to a general depression of movement.
6. Huntington’s disease is a hereditary disorder (autosomal dominant) that is
characterized by choreiform movements and progressive dementia.
a. .Describe the pathological findings which lead to this condition and the effects which they
produce.
Pathological findings include severe cell loss in the striatum, leading to reductions in the number
of GABA neurons in this region. The first to be affected appear to be the GABA/enkephalin
containing neurons in the striatum, projecting to the external Globus Pallidus. This loss of
inhibitory input to the external pallidal segment increases the tonic inhibitory pallidal influence
on the subthalamic nucleus. This makes the subthalamic nucleus less effective in opposing the
action of the direct pathway. This leads to increased disinhibition of the thalamus and thus
increased excitation of the cortex.
b. Diagram the relevant circuitry involved in this disorder, showing the areas where there
are changes in the degree of afferent or efferent projections, thus producing the observed
condition.
Telencephalon notes, pg. 10
7. What do we need to know about the Nucleus accumbens?
First of all, know its general anatomical location and that it is considered
part of the ventral striatum. Secondly, know that it is associated with the
basal ganglia and the limbic system. Thirdly know that it receives
dopaminergic inputs from then ventral tegmental area of the mesencephalon
and has connections with the amygdala of the limbic system. Finally, be
familiar with the possible involvement in the mediation of pleasure and
euphoria.