Q3: Neurology: Basal Ganglia

Front 1

What is the BASAL GANGLIA?

Back 1

A group of nuclei in the brain interconnected with the cerebral cortex, thalamus and brainstem. Mammalian basal ganglia are associated with a variety of functions: motor control, cognition, emotions and learning.
MADE UP OF: CAUDATE, PUTAMEN, GLOBUS PALLIDUS

Hint 1

What three things does it interconnect?

What 5 functions is it associated with?

What 3 things is it made up of?

Front 2

OVERVIEW: A) What parts of the brain control movement?
B) What part controls Movement modulation?

Back 2

A)
1) Cortical areas
parietal, premotor, supplemental motor area
2) Descending tracts
pyramidal system
B)
Cerebellum and Basal Ganglia

Front 3

Where does movement that requires significant planning start?

Back 3

It starts in the parietal cortex, POSTERIOR to the postcentral gyrus.
You first see activity in the PREMOTOR CORTEX and then in the MOTOR CORTEX

Front 4

A)In the INITIATION OF MOVEMENT, in what two places does activity of neurons take place and when?

B) When do you get the greatest amount of activity?

Back 4

A)In all but the simplest movements, you get activity in the neurons of the basal ganglia and cerebellum (in lat hemisphere) even BEFORE the movement starts and BEFORE you get activity in the primary cortex.

B) You get the most activity when the movement is novel.

Front 5

Why do we want to learn about the basal ganglia?

Back 5

1) Want to understand basic movements
2) Want to understand circuitry of normal movement
3)und signs of pathological process
4)know current info
5) how patients with deficiencies respond to meds

Front 6

What is the main hypothesis regarding basal ganglia activity?

Back 6

"The model proposes that behaviors generated from the cerebral cortex are focused and facilitated by projections through the basal ganglia. These behaviors vary from species to species. Furthermore, the basal ganglia function to suppress other conflicting activities while reinforcing ongoing behaviors.”

Front 7

KEY CONCCEPTS:
A) What is the basal ganglia?
B) What is the major INPUT/ OUTPUT of the basal ganglia? Where do its fibers go?
C)How does direct pathway facilitate movement?
D)Indirect?
E) What loop modulates ecpression of movements, behavior, and cognition?
F) What might lesions in basal ganglia cause?

Back 7

A)a group of interconnected forebrain, diencephalon, and midbrain nuclei lying deep in the subcortical white matter, consisting of the striatum (caudate nucleus, putamen), globus pallidus, subthalamic nucleus and substantia nigra

B)Striatum (caudate and putamen) with widespread cortical input/ OUTPUT: Globus pallidus interna to frontal cortex via thalamic relay nuclei

C)Direct: releasing upper motor neurons form tonic inhibition

D)Indirect: modulates disinhibitory pathway of direct pathway

E) cortico-striato-pallidal-thalamo-cortical loop

F) Disorders in moevement, behavior, and cognition

Front 8

A) What is EXTRAPYRAMIDAL?
B) What are the 4 nuclei of the BASAL GANGLIA?

Back 8

a) It denote the basal ganglia as discussed in order to distinguished this from area of primary cortex and the pyramidal motor circuits. This from areas of primary and motor cortex function.

B)
1) Striatum (caudate, putamen)‏
2) globus pallidus (lateral and medial divisions)‏
3) substantia nigra (pars reticulata and pars compacta)‏
4) subthalamic nucleus (pars compacta and pars reticulata)

Front 9

What can be found in the DORSAL and VENTRAL parts of the STRIATUM?

Back 9

1) Dorsal: Caudate and putamen
2) Ventral: Nucleus accumbens

Front 10

What are the AFFERENT and EFFERENT projections to and from the LATERAL GLOBUS PALLIDUS?

Back 10

AFFERENT: input form striatum
EFFERENT: projects fot he subthalamic nucleus, inhibiting it

Front 11

In efferent projections of LATERAL globus pallidus, where does SUBTHALAMIC NUCLEUS project to?

Back 11

Medical globus pallidus

Front 12

Where does the MEDIAL GLOBUS PALLIDUS receive AFFERENT projections?

Back 12

Afferent:
EXCITATORY input: subthalamic nucleus
INHIBITORY input: (GABA) input from the striatum

Front 13

Where does the MEDIAL globus pallidus send EFFERENT projections?

Back 13

Efferent:
1) Lenticular fasciculus - arises from the medial globus pallidus and courses across the internal capsule to the VA-VL

2)Ansa lenticularis - arises from the medial globus pallidus and loops below the internal capsule to the VA-VL

3)Where the lenticular fasciculus and the ansa lenticularis join to enter the VA-VL they are termed the thalamic fasciculus

Front 14

Where do teh VA-VL of the thalamus project to?

Back 14

They project to the MOTOR CORTEX (precentral gyrus) and PREMOTOR CORTEX (in front of precentral gyrus- - all involved in planning of movement)

Why most of the basal ganglia have INDIRECT effect on movement by affectin OUTPUT of cerebral cortex

Front 15

A) What does the SUBSTANTIA NIGRA do?

B) What happens if you get degeneration of this?

Back 15

A) It provides DOPAMINE to the STRIATUM

B) Parkinson's Disease

Front 16

What are 4 functions of the STRIATUM?

Back 16

1) Gets input from all areas of the cortex: glutamate and dopamine from SN

2) Striosome and matrix portions: input form limbic

3) Most are medium spiny neurosn: GABAergic and quiet unless have movement or stimulation

4) Some inhibitory interneurons: NO

Front 17

What is the structure of the STRIATUM?

Back 17

Convergence
1) Cortex
widespread input

2) Striatum
75 million neurons

3) Globus pallidus
0.7 million neurons

Front 18

What is the CELLULAR organization of the striatum?

Back 18

Medium Spiny Neuron (MSN)‏
1) Input:
Glutamate
Dopamine
2) Output:
GABA

Front 19

A) Where does GLOBUS PALLIDUS PARSINTERNA receive inhibitory input from?


B) What is the major OUTPUT of the GPi/ SNr?

Back 19

A) GABAergic/ striatum

B) Major output form GPi/ SNr is inhibitory to the thalamus

*NOTE: GPi and SNr are functionally the SAME

Front 20

What is the CELLULAR organization of the GPi/ SNr?

Back 20

1) Segregation:
Parallel circuits
Paucity of interneurons
Electrophysiology

and/or

2)Integration:
Convergent signals

Front 21

What are FUNCTIONAL CONSIDERATIONS related to CONNECTIVITY?

Back 21

1) Scaling:
Temporal interplay between the direct and indirect pathway
amplitude
velocity
comparator function

2)Focusing:
cortical selection of movements
center-surround mechanism
indirect pathway terminates broadly
direct pathway terminates narrowly

Front 22

What are the functions of the GPi/ SNr?

Back 22

1) Parkinson's Disease: rigid slow movements, trouble initiating movements, tremors

2) abnormal movements at rest: chorea, athetosis, dystonia

Front 23

What is the DISINHIBITORY CIRCUIT?

Back 23

*The permissive role of the basal ganglia in the initiation of movement is perhaps most clearly demonstrated by the observations of eye movement control.

Front 24

A) What are the 2 pathways through the basal ganglia?

B) What is the DIRECT pathway involved in?

Back 24

A) Direct and Indirect

B) Involved in facilitation movement and indirect inhibition of it as well

Front 25

Describe the DIRECT and INDIRECT pathways

Back 25

The striatal projections from the median spiny neurons of the caudate and putamen send out projections that terminate in another pair of nuclei and basal ganglia complex termed the globus pallidus and the substantia nigra pars reticulata nuclei are in turn the major sources of output from the basal ganglia. t the globus pallidus and subsection either partial allowed to have some output functions and in fact are actually part of the globus pallidus. The striatal projections to these think that resemble the cortical stride. Pathways and that they terminate in rostrocaudal bands locations of which very with implication of their sources in the stria a striking feature of the projections from them up needing spiny neurons to the globus pallidus and such an option I is the degree of convergence onto palatal particular to sell the be fared neurons of the internal globus pallidus and the substantia nigra together to price the major pathways at length the basal ganglia with upper motor neuron’s in the cortex and brain stem

the subdivision between the substantia nigra parser take a lot of and globus pallidus internal segment are superficial and are actually one functional unit. However, there are differences in their projections intact the substantia nigra parser take a lot a project directly to the superior clitoris by analogy be globus pallidus internal segment projects directly to the ventral anterior and ventral lateral thalamic nuclear complex. The upper motor neuron’s in the Spirit comatose command I movements without an intervening delay in the thalamus. However the particular to ask phones also project to the thalamus where they contact really neurons that project to the frontal eye fields of the premotor cortex.

Front 26

Describe: Projections within the Basal Ganglia: Direct Pathway

Back 26

The projections from the medium spiny neurons of the caudate and putamen to the internal segment of the globus pallidus and the substantia nigra pars reticulata are part of a direct pathway and serve to release the upper motor neuron’s from tonic inhibition. in the direct pathway, transiently inhibitory projections from the caudate and putamen project into tonically active inhibitory neurons in the internal segment of the globus pallidus. The neurons from the internal segment of the globus pallidus intern project to the ventral anterior and anterolateral complex of the thalamus. Transient excitatory inputs to the caudate and putamen from the cortex and substantial right or are also shown as is the transiently excitatory input from the thalamus back to the cortex

Let us imagine a scenario to help us illustrate how the basal ganglia facilitate movement. Note that the globus pallidus internal segment is tonically active inhibiting output from the thalamus to the frontal cortex. This tonic in addition serves as a way to prevent undesirable movements when they are not necessary. Imagine now the conscious act of raising and arm in order to push and elevator button. The cerebral cortex fires transiently excitatory input into the caudate and putamen. In addition to firing of axons to the upper and lower motor neuron units to raise the arm, a general program to release tonic in addition to allow the arm to move occurs. This transient excitation of the caudate and putamen results and transient suppression of the tonic in addition. Also it worked is the substantia nigra pars compact to wear dopamine helps facilitate this movement. This is not the only action of dopamine however.

Front 27

Describe: Projections within the Basal Ganglia: Indirect Pathway

Back 27

The direct pathway which facilitates movement is modulated by an additional pathway termed the indirect pathway. This circuit acts as a brake on the direct pathway. Let us revisit the scenario again where we are sending a program from the cortex to move the arm to push the elevator button. The excitatory cortical input to the indirect pathways activates medium spiny neurons of the striatum This transient inhibitory discharge, inhibits the tonically active GABAergic inhibitory output of the external globus pallidus. While it sends inhibitory output directly to the internal GP, the main effect is to transiently inhibit the tonic inhibition of the STN. This in turn transiently allows STN excitatory glutamatergic activity to the internal GP. This toactivated by the signals from the cortex, the medium spiny neurons discharge and inhibit the tonically active GABAergic neurons in the external globus pallidus. As a result the subthalamic cells become more active and by virtue of their excitatory glutamatergic synapses with the cells of the internal globus pallidus and reticulata, they increase the inhibitory outflow of the basal ganglia

Front 28

A) What are the different types of neurons in the striatum?

B) What are the patchwork of neurotransmitters?

C) What happens with the constituitive firing activity?

Back 28

A)
1)Mesium spiny neurons
2)Cholinergic interneurons
3)Enkehalinergic interneurons
4)Projection neurons all contain GABA

B) -

C)
1)It's an intrinsic pacemaker of membranes
2)Input affects firing rate and type

Front 29

What is the PROJECTION PATTERN?

Back 29

The projection pattern is highly topographic
1) Sensorimotor areas - central & caudal putamen
2) Frontal eye fields - body of caudate
3) Association areas - caudate and rostral putamen
4) Limbic areas - ventral striatum and olfactory tubercle

Front 30

*3) What are the AFFERENT and EFFERENT nuclei/ projections of the SNr?

Back 30

Afferent:
Caudate and Putamen

Efferent:
The substantia nigra pars reticulata projects to the mediodorsal thalamic nucleus and the brain stem reticular formation and superior colliculus
Therefore, it can feed back on the cerebral cortex or may influence motor function more directly through tectospinal or reticulospinal tracts

Front 31

What are functional observations regarding the function of teh basal ganglia?

Back 31

The predominant theories for function of the basal ganglia include a role in establishment of motor patterns (probably stored in the cerebral cortex) and then a role in accessing these motor programs

Front 32

What are 3 characteristics of Parkinson's Disease?

Back 32

1) Akinesia, resting tremor, rigidity, delayed postural corrections

2) Caused by degeneration of the substantia nigra pars compacta (loss of dopamine to the striatum)
‏
3) The net result is less tonic dopamine effect on the output of the striatum
a) Less excitation of the direct pathway and less inhibition of the indirect pathway
b) The net result is less excitatory feedback to the cerebral cortex from the VA/VL of the thalamus

Front 33

How would you treat PD?

Back 33

1) Treatment
Dopamine replacement by use of precursors (L-dopa) or stimulators
May use anticholinergic medicines
2) Pallidotomy
Carefully placed lesions of the medial globus pallidus may reduce akinesia by reducing inhibitory pressure on the VA-VL, thereby facilitating cortical movement
3) DBS
STN
GPi

Front 34

What is Hyperkinesias?

Back 34

A)Chorea:
1) Quick, jerky, random involuntary movements
2) Can be caused by striatal degeneration (such as Huntington's disease)
3) May be caused by excess of dopamine function

Front 35

What are Other hyperkinesias?

Back 35

B)Athetosis:
Slow writing, snakelike movements caused by many lesions, primarily of the striatum
C) Dystonia
Twisting of the limbs, trunk or neck due to structural or functional abnormality of the basal ganglia
D)Hemiballism
Due to lesion
s of the subthalamic nucleus (usually strokes)‏

Front 36

A)What are the Basal ganglia loops and Nonmotor functions?

B)What are teh 4 Parallel Circuits?

C)What are the segrated functions?

Back 36

A)

B)
Parallel Circuits
Cortical regions
Striatal regions
Pallidal nucleus
Thalamic nucleus

C)

Traditionally, the basal ganglia have been regarded as motor structure that regulate the inition of movemnet. However,the basal ganliga ar also central strucures in antomical cicuits or loops that ar involve din mdulationg non-motor aspects of behavior. These parallel loops orginate in broad regions of the cortex, engage specific subdivisions of the basal galnglia and thalamus, and ultimately terminate in areas of the frontal lobe outside the primary motor and premotor cortices. These non motor loops include a prefreontal loop involving the dorsolateral prefrontal cortex an dpart of the caudate. A limbic loopinvolving the cingulate cortex and the ventral striatum, and an oculomotor loop that modulates the activity of the frontal eye fields. The anatomical smilarity of these loops to the traditional motor loop suggests that the non-motor regulatory functions of the basal ganalgia may be gnerally the same as what the basal ganglia do in regulating the initiation of movement. For example, the prefrontal loop may regulate the initiation and termination of cognitive processes such as planning, working memory, and attention. By the same token, the limbic loop may regulate emotional behavior and motivation. This is important because we deal with diseases and treatments that potentially alter these nonmotor loops and their manifestation of cognitive and emotional deterioration can be seen in HD and PD.

Front 37

What is the VENTRAL STRIATAL SYSTEM?

A) Where is it located?

B) What does it consist of?

C) Where do AFFERENTS arise?

Back 37

A) Located ventral to the striatum

B) Nucleus accumbens and ol' factory tubercle

C) AFFERENTS arise from limbic cortex including the hippocampus, amygdala, piriform cortex, cingulate cortex and entorhinal cortex

Front 38

What is the ventral pallidum? What does it also regulate?

Back 38

1) This projects to the mediodorsal nucleus of the thalamus which in turn projects to the prefrontal and anterior cingulate cortex
2) This is also involved in regulating head and eye movements (attention) and visceral reactions (emotions)‏