basal ganglia

Question 1

1. Give a general description of the role of the basal ganglia in motor control.

Answer 1

Modulation of motor performance by massive interconnections with motor cortices

Question 2

2. What is the major source of input to the basal ganglia? And which are the input/output nuclei

Answer 2

cerebral cortex. The caudate and putamen are input nuclei b/c they are closest to the cortex. Info flows from caudate and putamen to globus pallidus, then to the thalamus and back to cortex, so globus pallidus is major output nucleus

Question 3

why are basal ganglia most susceptible to metabolic disruption

Answer 3

Basal ganglia are enriched in neurotransmitter biosynthesis (ie 80% of dopamine in the brain is here)

Question 4

3. Describe the character and probable cause of Parkinson’s disease.

Answer 4

Difficulty in initiating movement or performing sequential complex movements. Caused by degeneration of substantia nigra neurons and loss of dopamingergic input

Question 5

List the nuclei of the basal ganglia

Answer 5

caudate and putamen (collectively called neostriatum), globus pallidus (external and internal portions), substantia nigra and subthalamic

Question 6

Principal output nucleus of basal ganglia

Answer 6

Internal portion of globus pallidus

Question 7

Do basal ganglia control ipsilateral or contralateral body

Answer 7

Because the basal ganglia on one side interact with the cortex on that same side, unilateral defects in the basal ganglia are seen as contralateral deficits in function. That is, the left basal ganglia control movements of the right side of the body (in contrast to the cerebellum).

Question 8

List function of the basal ganglia nuclei

Answer 8

neostriatum: inputs from cortex. Globus pallidus: outputs to thalamus. Substantia nigra: internal feedback loops. Receives projections from striatum and projects back to striatum or to the thalamus. Subthalamic: receives projection from external segment of globus pallidus and projects back to external and internal globus pallidus (pallidal feedback loop)

Question 9

Which specific part of cortex projects to the Putamen and where do fibers go from putamen

Answer 9

Sensori-motor cortex projects to putamen. Putamen in turn projects to its own subsection of globus pallidus, which in turn projects mostly to VA (some VL) thalamus. These thalamic nuclei in turn project back to motor cortex, especially supplementary motor area (SMA)

Question 10

Which specific part of cortex projects to the caudate and where do fibers go from there

Answer 10

The caudate receives input widely from frontal association cortex (the frontal lobes), sends its information to its own region of globus pallidus, and from there to dorsomedial thalamus, which in turn projects widely to association cortex

Question 11

What is the nucleus accumbens and what is its function

Answer 11

Caudal juncture btw caudate and putamen. it processes information from paleo-cortex (near olfactory cortex) as part of the limbic system and subserves emotional and drive related aspects of behavior

Question 12

which basal ganglia has a somatotopic map

Answer 12

putamen

Question 13

4. Is the output of the basal ganglia inhibitory or excitatory?

Answer 13

Output of basal ganglia are Inhibitory!!!

Question 14

Describe the direct pathway from cortex to basal ganglia

Answer 14

1. Cells in layer V of cerebral cortex (output cells) send axons to synapse in basal ganglia where they release glutamate to excite cells in caudate or putamen. 2. Cells in caudate or putamen send axons to globus pallidus where they release GABA to inhibit cells there. 3. The cells in globus pallidus send axons to thalamus where they release GABA to inhibit
   cells there. 4. Thalamic neurons can then excite cells in cortex1. Cells in layer V of cerebral cortex (output cells) send axons to synapse in basal ganglia where they release glutamate to excite cells in caudate or putamen. 2. Cells in caudate or putamen send axons to globus pallidus where they release GABA to inhibit cells there. 3. The cells in globus pallidus send axons to thalamus where they release GABA to inhibit
   cells there. 4. Thalamic neurons can then excite cells in cortex1. Cells in layer V of cerebral cortex (output cells) send axons to synapse in basal ganglia where they release glutamate to excite cells in caudate or putamen. 2. Cells in caudate or putamen send axons to globus pallidus where they release GABA to inhibit cells there. 3. The cells in globus pallidus send axons to thalamus where they release GABA to inhibit
   cells there. 4. Thalamic neurons can then excite cells in cortex

Question 15

Basal firing rate of basal ganglia

Answer 15

Globus pallidus neurons fire spontaneously at high rates, while striatal neurons fire very slowly. In absence of cortical input, globus pallidus inhibits thalamo-cortical input. A signal will excite striatal neurons causeing inhibition of pallidus and disinhibiting thalamo cortical pathway. This leads to positive feedback to cortex

Question 16

Describe pathway of substantia nigra activation

Answer 16

Striatal neurons release GABA to inhibit substantia nigra. When substantia nigra is not inhibited, it sends dopaminergic axons back to the striatum where dopamine is excitatory. Dopamine is released diffusely, perhaps humorally, into striatum. DA is excitatory to GABA-ergic output neurons but may be inhibitory to cholinergic interneurons in the striatum

Question 17

D1/direct pathway

Answer 17

excitatory pathway: cortex releases glutamate and excites medium spiny neurons in caudate and putamen > striatum release GABA and inhibit globus pallidus internal > Gpi does not release GABA at thalamus thus thalamus is excited > thalamus excites cells in cortex

Question 18

dopamines and acetylcholines effect on D1 pathway

Answer 18

dopamine is excitatory to striatum, so overall it will lead to excitation of cortex via D1 pathway. Acetylcholine has opposite effect

Question 19

Pathway of subthalamic nucleus activation

Answer 19

The subthalamic nucleus receives an inhibitory input from external (lateral) globus pallidus and projects excitation back to the internal (medial) segment of globus pallidus. The functional consequence of a blow-out (“vascular accident”) of the subthalamic nucleus is equivalent to disinhibition of thalamus, that is, loss of excitation to inhibitory neurons of globus pallidus

Question 20

D2/indirect pathway

Answer 20

inhibitory pathway: cortex releases glutamate and excites medium spiny neurons in striata > striata release GABA and inhibit globus pallidus external > Gpe inhibits subthalamic nucleus > STN excites internal globus pallidus > Gpi releases GABA at thalamus and inhibits it > no excitation of corte

Question 21

dopamine and acetylcholines effect on D2 pathway

Answer 21

dopamine is excitatory to striatum, so overall it will lead to inhibition of cortex via D2 pathway. Acetylcholine has opposite effect

Question 22

Which disorders of basal ganglia are due to direct vs indirect pathway involvement

Answer 22

Hypokinetic disorders are due to decrease in direct pathway. Hyperkinetic disorders are due to decrease in indirect pathway

Question 23

Describe the physical characteristics of Parkinsons

Answer 23

resting tremor- stops during intended movement. Increased tone due to activation of flexors and extensors simulataneously, difficulty in initiating movements, slowness of movement

Question 24

Describe the brain structures affected by Parkinsons

Answer 24

Loss of dopamine neurons on substantia nigra. Since dopamine is excitatory to striatal neurons, this reduces disinhibition that striatum would produce in thalamus by way of globus pallidus.

Question 25

Drug with Parkinsonian like effects

Answer 25

MPTP- causes death of dopaminergic cells in substantia nigra

Question 26

Parkinsons treatment

Answer 26

L-dopa (ingested, crosses BBB), carbidopa (blocks degradation of dopamine), brain transplants (inject catecholaminergic tissue from brains of aborted fetuses into patients basal ganglia), deep brain stimulation

Question 27

How does deep brain stimulation work

Answer 27

electrodes implanted in subthalamic neucleus or internal globus pallidus to stimulate neurons. Used for patients who still benefit from meds, but are disable by fluctuations btw on and off med states, or by med induced dyskinesias.

Question 28

Chorea

Answer 28

Nearly continuous rapid movements of face, tongue or lips

Question 29

Athetosis

Answer 29

slow, writhing, ceaseless movements of hand, sometimes lips, tongue, neck and foot

Question 30

symptoms of Huntingtons

Answer 30

chorea or athetosis. Initially, relative hypokinesia or immobility, degradation of mood, loss of computational and memory skills

Question 31

5. What is the genetic cause of Huntington’s Disease

Answer 31

Autosomal dominant- triplet repeat of CAG in the Huntingoton gene on Short arm of 4th chromosome. This codes for polyglutamine. 17-34 repeats is normal, >40 causes Huntingtons

Question 32

What areas of the basal ganglia are affected in Huntingtons

Answer 32

Cholinergic striatal neurons and GABAergic medium spiny output neurons of striatum degenerate, possibly due to glutamate excitotoxicity. Loss of striatal actions on globus pallidus seem to cause dz symptoms. Too much exogenous dopamine can also produce symptoms

Question 33

Dopamine axis in basal ganglia

Answer 33

Too little dopamine produces lack of movement (Parkinsonism), too much dopamine produces hyperkinesia (Huntington’s chorea) (leading to the analogy that dopamine acts as “brain grease”).

Question 34

Hemiballismus- what is it, what causes it

Answer 34

Flailing movements of th arm and leg on one side. This results when a stroke in a small ganglionic branch of the posterior cerebral artery leads to damage of the subthalamic nucleus on one side (usually in the elderly). Loss of excitation by the subthalamic nucleus reduces inhibitory outflow of globus pallidus so motor programs are inappropriately initiated through the disinhibited thalamus.

Question 35

What type of stimulus (depolarizing or hyperpolarizing) would you predict would be used for the “deep stimulation” treatment of Parkinson patients?

Answer 35

not sure yet