Presentation by Andreas Schleicher Tackling the School Absenteeism Crisis 30 ...
mink_presentation.ppt
1. Basal Ganglia
Jonathan W. Mink, MD PhD
Depts. Of Neurology, Neurobiology &
Anatomy, Brain & Cognitive Sciences,
and Pediatrics
University of Rochester (NY)
2. What and Where Are the Basal
Ganglia?
The basal ganglia are interconnected nuclei in
the telencephalon, diencephalon and
mesencephalon
Input comes from virtually all of cerebral cortex
Output goes to frontal lobes via thalamus and to
brainstem
No direct input or output connections with spinal
cord
3.
4. Constituent Nuclei of the Basal
Ganglia
Striatum
Caudate nucleus (= tailed)
Putamen (= shell)
Nucleus accumbens septi (=leaning against the
septum)
10. Constituent Nuclei of the Basal
Ganglia
Subthalamic nucleus (STN)
Substantia Nigra (= black substance)
– Pars reticulata (SNpr)
– Pars compacta (SNpc)
Ventral Tegmental Area (not always included)
13. What Do the Basal Ganglia Do?
A primary role of the basal ganglia is in motor control
Largest inputs and outputs are to and from motor areas
Neuronal discharge in the basal ganglia correlates with
movement
Basal ganglia lesions cause movement abnormalities
Other important roles
Cognition
Emotion
Motivation
14. Historical Schemes of Basal
Ganglia Function
Extrapyramidal motor system
Phylogenetically "old" system that controls posture
and "automatic" movements
Output to brainstem reticular formation
Basal ganglia diseases result in abnormal postures
15. Historical Schemes of Basal
Ganglia Function
"Prepyramidal" system that initiates movement
Basal ganglia increase in size in parallel to frontal
lobes during phylogeny
Output to motor areas of cortex via thalamus
Basal ganglia diseases result in abnormal excessive
movements that resemble normal movements or in
slow and small movements
16. Historical Schemes of Basal
Ganglia Function
More data show that the basal ganglia output is
inhibitory, and thus is unlikely to generate either
posture or movement.
It is now known that the output is to both
brainstem and thalamus and is thus both "extra-"
and "pre-pyramidal".
17. Current Scheme of Basal Ganglia
Motor Function
When a voluntary movement is to be made,
cerebral cortical and cerebellar mechanisms act
to initiate and coordinate the movement
The basal ganglia act in parallel to allow the
desired motor program to proceed and to inhibit
motor mechanisms that would otherwise
compete with the one which has been initiated
18.
19. Striatum (Caudate / Putamen)
Five neuron types
Medium spiny neurons are output neurons with extensive
local collaterals and make up 95% of the total. Although they
are morphologically homogeneous, they are chemically
heterogeneous
Large aspiny neurons (1-2%) are interneurons that use ACh
as a neurotransmitter.
Medium aspiny neurons (1%) are interneurons that use
somatostatin as a neurotransmitter.
GABAergic interneurons (1-2%). Best known are the
parvalbumin positive fast-spiking interneurons.
21. Striatum
Input from virtually all areas of cerebral cortex
(except primary visual and primary auditory
cortex)
Cortical input is excitatory and glutamatergic
25. Striatal Organization
Within the striatum there is a patchy striosome and
matrix organization
Demonstrated with AChE stain (striosomes are pale)
Matrix
– Bulk of striatal volume
– Receives input from most areas of cortex
– Bulk of output to globus and SNpr from matrix
Striosomes
– Receive input from prefrontal cortex
– Output primarily to SNpc
32. Subcortical Inputs to Striatum
Thalamus (CM-PF and VL)
– Excitatory and glutamatergic (presumed)
– Function and significance unknown
Substantia nigra pars compacta
– Dopaminergic
– Termination is largely presynaptic on cortical afferents
and on shafts of dendritic spines
– Multiple types of receptors divided into two classes
D1 - facilitatory, in greater numbers on Dyn/SP cells
D2 - inhibitory, in greater numbers on ENK cells
38. Subthalamic Nucleus
Subthalamic Nucleus
Two neuron types
– GPi projecting
– GPe projecting
Input from frontal lobe areas
– Cortical input is excitatory and glutamatergic
– Somatotopy preserved
Output to GPi, GPe, and SNpr is glutamatergic and
excitatory
39.
40. Basal Ganglia Output Nuclei
Globus Pallidus pars interna
Substantia Nigra pars reticulata
41. Globus Pallidus pars interna
Composed of large projection neurons
Radial dendrites spanning almost 1 mm in diameter
Dendrites oriented perpendicular to incoming striatal
afferents
44. Pallidal Inputs
Striatal and subthalamic inputs terminate in different
patterns
– Each striatal axon contacts several neurons en passant
before ensheathing a single neuron
– Each subthalamic axon ensheathes a number of neurons
– Input from STN is faster that input from striatum
47. Timing
Timing of movement-related activity in the basal
ganglia is late in relation to movement onset
Activity of GPi output for limb movements is after
onset of muscle activity
For eye movements, SNpr activity is late relative
to initiatory activity in superior colliculus
50. GPi outputs
Output is GABAergic and inhibitory
– 80% project to VL/VA thalamus which in turn project to
frontal lobes
Supplementary motor area
Premotor cortex
Motor Cortex
Prefrontal Cortex
– Collaterals of thalamic projection go to pedunculopontine
area at midbrain/pons junction which in turn projects to
reticulospinal system
Thus output is both "extrapyramidal" and "prepyramidal"
51. Substantia nigra pars reticulata
Generally similar to GPi and may be functionally part of same
structure that is partitioned by the internal capsule
Pattern of input from striatum and subthalamic nucleus is
similar
Output is GABAergic and inhibitory to VA/VLo/VLm thalamus
as well as to part of MD thalamus
Collaterals to pedunculopontine area
Projection to CM-PF thalamus
Primary difference is projection of lateral portion to superior
colliculus and to DMpl thalamus (projects to frontal eye fields)
52. Cortical Targets of BG Output
(Alexander et al., 1986)
(Middleton and Strick, 2000)
55. Globus Pallidus pars externa
Intrinsic nucleus that focuses activity of output nuclei
Inputs from subthalamic nucleus and striatum (similar to GPi
and SNpr)
Two types of neurons, both project out of GPe
Output is GABAergic and inhibitory
– Projection to subthalamic nucleus
– Projection to GPi/SNpr that terminates proximally on cell bodies
– Recently described projection back to striatum
56.
57. Substantia Nigra pars compacta
Dopamine containing neurons that project
diffusely to striatum as described above
Modulates the direct and indirect pathway in
opposite directions
58.
59. SNpc Activity
Low activity rate (2 Hz)
No movement-related activity
No apparent somatotopy
60. SNpc Activity
Neuron activity is related to "significant" events
such as reward or presentation of instructional
cues, but carry little specific information
regarding modality or spatial properties.
No clear responses to stimuli unless in the
context of a movement task.
65. Dopamine Modulation of Striatal Projection
Neurons is State-Dependent
Action of dopamine via D1 receptors
depends on resting membrane potential of
medium spiny cell
Dopamine may mediate both LTP and LTD
Post-synaptic mechanisms are critical and
may be involved in abnormal dopamine
neurotransmission
74. Surface EMG in subject with
Huntington Disease at Rest
0 5 10 15 20 25 30
Time (s)
Anterior Deltoid
Posterior Deltoid
Biceps
Triceps
Wrist Flexors
Wrist Extensors
75. (from Matsumura et al., 1995)
GPi Discharge in Chorea
Most, but not all GPi
neurons decrease in
association with
chorea/dyskinesia
The discharge pattern of
GPi neurons does not
appear to correlate with
individual movements in
chorea
76. Chorea Is Associated With Insufficient Inhibition
of Competing Motor Patterns
Excitatory
Inhibitory
Striatum
GPi
STN
Thalamocortical
Target
Desired
Motor Pattern
Competing
Motor
Patterns
Cerebral
Cortex
Excitatory
Inhibitory
Striatum
GPi
STN
Thalamocortical
Target
Desired
Motor Pattern
Competing
Motor
Patterns
Cerebral
Cortex
Involuntary
Motor Patterns
(Chorea)
Normal Chorea
77. Dystonia
A condition marked by sustained, abnormal,
twisting postures
Can be seen with damage to striatum or globus
pallidus
Can be seen without obvious pathology, but
there is evidence for basal ganglia dysfunction in
most types of dystonia
82. Dystonia Is Associated With Expansion of the Facilitatory
Center and Diminution of the Inhibitory Surround
Normal Dystonia
Excitatory
Inhibitory
Striatum
GPi
STN
Thalamocortical
Target
Desired
Motor Pattern
Competing
Motor
Patterns
Cerebral
Cortex
Excitatory
Inhibitory
Striatum
GPi
STN
Thalamocortical
Target
Desired
Motor Pattern
Competing
Motor
Patterns
Excitatory
Inhibitory
Striatum
GPi
STN
Thalamocortical
Target
Desired
Motor Pattern
Competing
Motor
Patterns
Cerebral
Cortex
Excitatory
Inhibitory
Striatum
GPi
STN
Thalamocortical
Target
Desired
Motor Pattern
Competing
Motor
Patterns
83. (from Gimenez-Amaya and Graybiel, 1991)
Modular Organization of Striatal Matrix
(Matrisomes)
Matrisome
84. (from Alexander and DeLong, 1985)
Striatal Microexcitable Zones
Microstimulation in the putamen elicits stereotyped
motor patterns that depend on site of stimulation
85. Tics Result From Multiple Specific Areas of Focused
Facilitation in an Otherwise Normal Inhibitory
Surround
87. Conclusion
Basal ganglia motor circuits are organized anatomically
and physiologically to selectively facilitate desired
movements and to inhibit potentially competing
movements
Lesions or diseases affecting the basal ganglia cause
movements disorders that can be understood as failure
to facilitate desired movements (e.g PD), failure to
inhibit unwanted movements (e.g chorea, dystonia,
tics), or both.
88. Selection and Inhibition of
Competing Motor Patterns
“The basal ganglia have all the aspects of a ‘clearing house’
that accumulates samples of ongoing projected activity
and, on a competitive basis, can facilitate any one and
suppress all others.”(Denny-Brown and Yanagisawa, 1976)
“We propose that this circuit is organized anatomically and
neuro-chemically so that the striatum can select and
maintain motor behaviors... Furthermore, the basal ganglia
function to suppress other conflicting activities while
reinforcing ongoing behaviors.” (Penney and Young, 1983)
