Week 5.3 Basal Ganglia & Dopamine

Primary motor role of the basal ganglia

Initiate movement, suppress unwanted movement, and stop ongoing movement

Do the basal ganglia have direct connections to LMNs?

No, they regulate UMN pathways only

How do the basal ganglia influence movement?

By turning motor programs on and off via inhibition and disinhibition

Five main nuclei of the basal ganglia

Caudate nucleus, Putamen, Globus pallidus, Substantia nigra, Subthalamic nucleus

What structures form the striatum?

Caudate nucleus and putamen

What structures form the globus pallidus?

Internal (GPi) and external (GPe) segments

Is the striatum inhibitory or excitatory?

Always inhibitory (GABAergic)

Primary input to the basal ganglia

Cerebral cortex via corticostriatal pathways

Which cortical areas send input to the basal ganglia?

Frontal association, parietal association, supplementary motor area

Neurotransmitter of cortical input to striatum

Glutamate (excitatory)

Secondary input to the basal ganglia

Substantia nigra pars compacta

Neurotransmitter released by substantia nigra pars compacta

Dopamine

Primary output nuclei of the basal ganglia

GPi and substantia nigra pars reticulata (SNpr)

Neurotransmitter of basal ganglia outputs

GABA (inhibitory)

Main targets of basal ganglia output

Thalamus, motor cortex, reticular formation, superior colliculus

Overall function of basal ganglia output

Inhibit motor activity

Define inhibition

A neuron prevents another neuron from reaching threshold

Define disinhibition

Inhibition of an inhibitory neuron, resulting in excitation

Functional meaning of disinhibition

Allows movement to occur

Three basal ganglia pathways

Hyperdirect, direct, indirect

Primary role of the hyperdirect pathway

Stop ongoing movements

Primary role of the direct pathway

Initiate intended movement

Primary role of the indirect pathway

Suppress unwanted competing movements

Hyperdirect pathway nickname

STOP pathway

Direct pathway nickname

GO pathway

Indirect pathway nickname

NO-GO pathway

Net effect of hyperdirect pathway

Increased inhibition of thalamus → stopping movement

Net effect of direct pathway

Disinhibition of thalamus → movement initiation

Net effect of indirect pathway

Inhibition of thalamus → suppression of unwanted movement

Role of the thalamus in motor control

Relay motor information to cortex

Why inhibition of the thalamus matters

Prevents motor cortex activation

Key functional principle of basal ganglia pathways

Balance between excitation and inhibition

Which pathway activates focused motor programs?

Direct (GO) pathway

Which pathways broadly suppress motor programs?

Indirect and hyperdirect pathways

Role of substantia nigra pars compacta

Modulates direct and indirect pathways via dopamine

Two dopamine receptors in the striatum

D1 and D2

Effect of D1 receptor activation

Facilitates direct (GO) pathway

Effect of D2 receptor activation

Suppresses indirect (NO-GO) pathway

Net effect of dopamine on movement

Movement facilitation

Are dopamine effects long-lasting?

No, they are transient and task-specific

Motor functions of the basal ganglia

Inhibit ongoing movement, select and execute movement, inhibit unwanted movement

Do basal ganglia act ipsilaterally or contralaterally?

Form motor loops within the same cerebral hemisphere

Non-motor loops of the basal ganglia

Prefrontal loop and limbic loop

Role of the prefrontal loop

Initiation and termination of cognitive processes

Examples of prefrontal loop functions

Attention, working memory, executive function

Role of the limbic loop

Regulation of emotional and motivated behavior

What disorders involve the limbic loop?

Parkinson's disease and Huntington's disease

Two broad categories of basal ganglia disorders

Hyperkinetic and hypokinetic

Define hyperkinetic disorder

Excessive movement due to insufficient thalamic inhibition

Define hypokinetic disorder

Difficulty initiating movement due to excessive thalamic inhibition

Primary hyperkinetic disorders

Huntington's disease, hemiballismus

Primary hypokinetic disorder

Parkinson's disease

Pathophysiology of Huntington's disease

Selective degeneration of caudate and putamen

Which pathway is affected first in Huntington's disease?

Indirect pathway

Net effect of Huntington's disease

Inability to suppress unwanted movement

Early symptoms of Huntington's disease

Chorea (dance-like involuntary movements)

Late symptoms of Huntington's disease

Dementia and cortical degeneration

Cause of Huntington's disease

Autosomal dominant mutation in huntingtin gene

Pathophysiology of hemiballismus

Lesion of the subthalamic nucleus

Key symptom of hemiballismus

Ballistic flinging movements of one limb

Side of symptoms in hemiballismus

Contralateral to lesion

Pathophysiology of Parkinson's disease

Degeneration of dopaminergic neurons in substantia nigra pars compacta

Effect of dopamine loss in Parkinson's disease

Direct pathway underactive, indirect pathway overactive

Net effect on thalamus in Parkinson's disease

Excessive inhibition

Core motor symptoms of Parkinson's disease

TRAP: Tremor, Rigidity, Akinesia, Postural instability

Define rigidity in Parkinson's disease

Velocity-independent resistance to passive movement

Gait characteristics in Parkinson's disease

Shuffling, freezing, festination, reduced step length

Facial expression changes in Parkinson's disease

Masked facies

Primary pharmacological treatment for Parkinson's disease

L-DOPA

Why dopamine cannot be given directly

Cannot cross the blood-brain barrier

How L-DOPA works

Dopamine precursor that crosses BBB and is converted in brain

Does L-DOPA cure Parkinson's disease?

No, it treats symptoms only

Complications of long-term L-DOPA use

Dyskinesias, wearing-off, on-off fluctuations

What is deep brain stimulation (DBS)?

Electrical modulation of abnormal neural activity

Primary DBS targets in Parkinson's disease

GPi and subthalamic nucleus

Goals of DBS in Parkinson's disease

Reduce off-time, improve on-time, reduce dyskinesia

Key conceptual summary of basal ganglia function

All gas and no brakes = hyperkinetic; all brakes and no gas = hypokinetic