Basal Ganglia & Motor Activity (Lecture 4/27/10)

Front 1

Specific nuclei of basal ganglia

Back 1

1) Neostriatum (composed of caudate & putamen)

2) Globus Pallidus (Lateral & Medial Segments: GPL & GPM)

3) Substania Nigra (Pars compacta & Pars reticularis)

4) Subthalamic Nucleus

Front 2

What is the major receptive area in basal ganglia?

What is the source?

Are they excitatory or inhibitory?

Back 2

Receptive: Neostriatum*
Major source: Cerebral cortex
(Minor): Thalamus
- Input is excitatory

*Cerebral cortex also sends minor projections to the substantia nigra & subthalamic nucleus.

Front 3

Which nuclei project outside of the basal ganglia?

What is their major target?

Are they excitatory or inhibitory?

Back 3

Output: 1) GPM 2) Pars reticularis
Major target: VA/VL Thalamus*
- Output is Inhibitory

*Pars reticularis sends a few projections directly to cerebral cortex, but we don't need to know anything else about these.

Front 4

Which NT do the nuclei of the basal ganglia produce?

What are their physiological effects?

Back 4

1) GABA: Inhibitory
- Neostriatum
- Globus Pallidus
- Pars Reticulata of S.N.

2) Glutamate: Excitatory
- Subthalamic Nucleus (the only exclusively excitatory nucleus of the B.G.)

3) Dopamine: Excitatory or Inhibitory (depends on the type of dopamine-R)
- Pars Compacta of S.N.

Front 5

Disinhibition

Back 5

"Removal of an inhibitory influence"

- The process used by the B.G. to influence the motor cortex.

-In a classic disinhibitory circuit:
an intermittently active INHIBITORY neuron synapses on-->
a tonically active INHIBITORY neuron, which synapses on -->
an EXCITATORY neuron.

--->Net result= the output of the excitatory neuron is increased.

(Intermittently inhibit the inhibitor.)

Front 6

Neostriatum

Back 6

Two neuronal types: medium spiny & large aspiny

NT produced: GABA

Afferents:
1) cerebral cortex (+)
2) thalamus (+)
3) pars compacta (+/-),
depends on dopamine-R. A given
neuron expresses only D1 (+) or D2 (-), but NOT both!

Efferents: All inhibitory
1) GPM
2) GPL
3) Pars compacta
4) Pars reticulata

- Abnormal in Huntington's

Front 7

GPL

Back 7

NT produced: GABA

Afferents:
major: 1) Neostriatum (esp. from D2)
minor: 2) Subthalamic nucleus
minor: 3) Pars reticulata

Efferents: All inhibitory
1) Subthalamic Nucleus

Front 8

GPM

Back 8

NT produced: GABA

Afferents:
1) Neostriatum (esp. from D1)
2) Subthalamic Nucleus

Efferents: All inhibitory
1) VA/VL Thalamus

- One of 2 nuclei that project outside B.G. (to the thalamus).

Front 9

Pars Compacta of the Substantia Nigra

Back 9

NT produced: Dopamine

Afferents:
major: 1) Neostriatum (-)
minor: 2) Cerebral Cortex
minor: 3) GPL

Efferents: Depends on dopamine-R. (D1/+, D2/-)
1) Neostriatum
- Accumulate neuromelanin, a dopamine-synthesis byproduct, which gives its color.

- Abnormal in Parkinson's

Front 10

Pars Reticularis of the Substantia Nigra

Back 10

NT produced: GABA

Afferents:
similar to GPM

Efferents: Inhibitory
similar to GPM

- The other of 2 nuclei that project outside B.G. (to the thalamus)

Front 11

Subthalamic Nucleus

Back 11

NT produced: Glutamate

Afferents:
major: 1) GPL
minor: 2) cerebral cortex & other sites

Efferents: Excitatory
1) GPM

- Located in the diencephalon.
- Lesions in this nucleus cause contralateral hemiballism

Front 12

Direct Motor Pathway

Back 12

Net effect: Increase DISinhibition of the thalamus

Steps:
1) Cerebral cortex projects (+) synapse onto intermittently active (-)D1neuron of Neostriatum.

2) The activated (-)D1 makes an (-)synapse onto tonically active (-)neuron of GPM.

3)The GPM's inhibitory influence on the VA/VL of the thalamus is interrupted.

4) The thalamus is now free to fire (+)projections to motor neurons in the cerebral cortex.

*A similar, parallel direct loop occurs through the pars reticularis.

Front 13

Indirect Motor Pathway

Back 13

Net effect: Increase INHIBITION of the thalamus

Steps:
1) Cerebral cortex projects (+) synapse onto (-)D2neuron of Neostriatum.

2) The activated (-)D2 makes a (-)synapse onto tonically active (-)neuron of GPL (**note different from direct!)

3) The GPL's inhibitory influence on the subthalamic nucleus is interrupted.

4) The subthalamic nucleus is now free to send a very powerful (+)projection to the GPM.

5) The (-)neurons of GPM are now excited and strengthen their inhibition of the thalamus.

6) Excitatory input from the thalamus to the motor cortex is decreased.

*Subthalamic n. also sends (+) signals to the pars reticularis, creating a parallel loop.

Front 14

Major function of the basal ganglia

Back 14

Planning, initiation, and cessation of complex voluntary movements

Front 15

Non-motor functions of the basal ganglia

Back 15

--> Prefrontal Loop
(originates in prefrontal & orbital frontal cortex), &
Limbic Loop (originates in amygdala & hippocampus):
- projects to DMN Thalamus
- influence cortical areas involved
in cognition, memory, emotion, & behavior

--> Connections to Ventral Tegmental Area & Nucleus Accumbens:
- Major role in pleasure-seeking and addictive behavior

Front 16

Hemiballism:
What damage is present and how does principal motor derangement develop?

Back 16

- Random, involuntary flinging of the limbs on 1 side of the body.

- Assoc. w/ lesions to contralateral subthalamic nucleus.

- Hyperkinesia:
1) Lesions to subthalamic n. interrupt excitatory projections to GPM.
2) GPM now exerts less inhibition on VA/VL thalamus.
3) Thalamus now increases excitation of the cerebral cortex.
4) Increased motor activity on the contralateral side of the body develops.

Front 17

Parkinson Disease:
What damage is present and how does principal motor derangement develop?

Back 17

- Bradykinesia, shuffling gait, stooped posture, rigidity, and a characteristic resting tremor. Some pts have dementia.

- Assoc. w/ loss of dopamine-secreting neurons in the pars compacta of the substantia nigra, along w/ presence of "Lewy" bodies.

-Hypokinesia:
1) Loss of dopaminergic neurons leads to decreased excitation of D1-R & decreased inhibition of D2-R neurons in the Neostriatum.
2) This leads to increased inhibition from the GPM to the VA/VL Thalamus

3) VA/VL inhibition decreases stimulation of the motor cortex.
4) Decreased motor activity develops.

Front 18

Huntington Disease:
What damage is present and how does principal motor derangement develop?

Back 18

- Autosomal Dominant, presence of abnormal, involuntary movements, behavioral abnormalities, and dementia. Some pts. develop rigidity.

- Hyperkinesia:
1) Loss of neurons in the caudate and putamen, resulting in their atrophy.
- Medium spiny neurons projecting to GPL are especially affected, particularly in early stages.
2) Decreased inhibition to the GPL results in an increased inhibitory signal to the subthalamic n.
3) This interrupts the subthalamic n. (+)projection to the inhibitory neurons of the GPM
4) This lowers the inhibitory signal to the thalamus.
5) The thalamus now increases excitation to the cerebral cortex.
6) Increased motor activity develops.