Basal Ganglia

What two nuclei combine to form the Lentiform Nucleus?

The globus pallidus and the putamen

Which structures comprise the Striatum?

The caudate and the putamen

Into which two specific parts is the Substantia Nigra divided?

The substantia nigra reticulata (SNr) and the substantia nigra compacta (SNc)

What is the primary neurotransmitter of the Striatum and Globus Pallidus?

GABA (inhibitory)

What is the primary neurotransmitter of the Subthalamic Nucleus?

Glutamate (excitatory)

What is the primary neurotransmitter of the Substantia Nigra?

Dopamine

What are the three primary pathways of the basal ganglia?

Stop (Hyperdirect); Go (Direct); and No-Go (Indirect)

Describe the “go” pathway

• Motor areas of the cortex release Glutamate onto the Putamen

• The Putamen is stimulated and releases GABA onto the Internal Globus Pallidus (IGP)

• The IGP is inhibited and releases less GABA onto the motor Thalamus, resulting in less inhibition/more excitation

• Motor Thalamus releases more Glutamate onto the Motor areas of the cortex, increasing stimulation of motor neurons

Describe the “No go” pathway

• Motor areas of the cortex release Glutamate onto the Putamen

• The Putamen is stimulated and releases GABA, inhibiting the External Globus Pallidus

• The Globus Pallidus releases less GABA onto the Subthalamic Nucleus

• The Subthalamic Nucleus is stimulated to release Glutamate onto the Internal Globus Pallidus

• The internal Globus Pallidus is stimulated to release GABA onto the Motor Thalamus to prevent unwanted movements

Describe the “stop” pathway

• Motor areas of the cortex release Glutamate onto the Subthalamic nucleus

• The subthalamic nucleus is stimulated to release Glutamate onto the Internal Globus Pallidus

• The Internal Glubus Pallidus releases GABA, inhibiting the Motor Thalamus, stopping ongoing movement

Purpose of the “Go” pathway

inhibition on an inhibitory area = excitation; to release a movement

Purpose of the “no-go” pathway

inhibit excess/unwanted movements

Purpose of the “stop” pathway

To stop ongoing movement

How does Dopamine affect D1 receptors in the putamen?

It excites the neurons

How does Dopamine affect D2 receptors in the putamen?

It inhibits the neurons

What is the main output structure of the basal ganglia to the motor thalamus and brainstem?

Internal globus pallidus (IGP)

What is the primary neurological cause of Parkinson’s Disease?

Death of dopaminergic neurons in the substantia nigra compacta (SNC)

What is the effect of dopamine loss on the internal globus pallidus (IGP) in PD?

Disinhibition/facilitation of the GPi (increased inhibitory output)

What are five common motor symptoms of Parkinson's Disease?

Rigidity; hypokinesia; bradykinesia; resting tremor; lack of postural reflexes

Honorable mention: difficulty initiating movements

What are the two hallmark characteristics of Huntington's Disease?

Choreiform movements; dimentia

Huntington’s disease: summarize effects on BG pathways

Increase in unintended movements (Stop)

Increase in unwanted extraneous movements (no go)

Uncontrolled voluntary movements (go)

What occurs in the basal ganglia circuitry during early Huntington's Disease?

Destruction of D2 neurons (No-Go) and overactivity of D1 neurons (Go)

Define Athetosis.

Slow; writhing-like involuntary movements due to damage to motor thalamus or striatum

Define Ballismus.

Large; repetitive; involuntary flailing movements due to damage to the subthalamic nucleus

Define Dystonia.

Involuntary; sustained postures or repetitive/twisting movements due to damage to the basal ganglia

Define focal dystonia

dystonia limited to one body region due to overactive Go pathway and underactive No-Go pathway

What are Pyramidal signs associated with the corticospinal tract?

Hypertonicity; hyperreflexia; and spastic paralysis

What non-motor functions do basal ganglia circuits contribute to?

Decision-making; emotions; learning; and judgment

What almond-shaped structure is near the tail of the caudate but not part of the BG?

Amygdala

At what stage of movement do basal ganglia neurons typically respond?

Prior to and during movement

Which two brainstem nuclei are major targets of the BG motor loop?

Pedunculopontine nucleus (PPN) and midbrain locomotor area (MLR)

Where does the cortex send its primary excitatory signal in the Stop (Hyperdirect) pathway?

Subthalamic Nucleus

The GPi sends inhibitory signals to the PPN; which spinal tract does the PPN influence?

Reticulospinal tracts

What is the role of the Midbrain Locomotor Region (MLR)?

Influences Stepping Pattern Generators (SPGs) and LMNs to facilitate walking

What gait abnormality in PD results from increased GPi inhibition of the reticulospinal tract?

Festinating gait

Name four non-motor signs of Parkinson's Disease.

Dementia; psychosis/hallucinations; sleep disturbances; and autonomic dysfunction

Which brain areas are involved in the circuit causing PD resting tremors?

Basal ganglia; cerebellum; thalamus; and motor cortex

How does the resting tremor in PD respond to L-DOPA compared to rigidity?

It typically responds less well

What neurological event characterizes the Late Stage of Huntington's Disease?

Death of D1 (Go pathway) neurons

Huntington’s disease: impact on the Stop pathway

Less excitatory output of the motor cortex → inhibition of the subthalamic nucleus → less inhibitory output of the iGP = unintended movements

Huntington’s disease: impact on the GO pathway

increased inhibition by the D1 neurons → increased inhibition of the iGP → decreased inhibition of the motor thalamus by the iGP = voluntary movements are uncontrolled

Huntington’s disease: impact on the No GO pathway

Less inhibitory output by D2 neurons → increased inhibition by eGP → inhibition of the subthalamic nucleus → less excitation of iGP → decreased inhibition of the motor thalamus by iGP = unwanted extraneous movements

Define Hemiballismus.

Unilateral large; repetitive; involuntary flailing movements caused by subthalamic nucleus damage

List characteristic signs of an Extrapyramidal lesion.

Dyskinesia; reduced postural reflexes; rigidity; and resting tremor