Basal ganglia - smbs.buffalo.edu · Basal ganglia Learning Objectives • Describe the function of the Basal Ganglia in movement • Define the BG components and their locations •

Basal ganglia

Sujata Sofat, class of 2009

Basal gangliaLearning Objectives

• Describe the function of the Basal Ganglia in movement

• Define the BG components and their locations

• Describe the motor loop of the BG

• Describe the direct motor circuit of the BG and how it functions

• Describe how the indirect motor circuit influences BG function

• Describe how the substantia nigra influences BG circuits

• Describe the symptoms of BG diseases and explain the vocabulary of movement disorders

• Describe the types of BG diseases, nuclei involved, and current treatments for Parkinson’s Dis.

http://nba.uth.tmc.edu/neuroscience/s3/chapter04.html

Overview

1. UMN activity in cortical motor areas is not great enough by itself to cause movement. So, it must get a boost – by the Basal Ganglia.

2. Basal Ganglia - 5 nuclei in cerebral hemispheres and brainstem.

Chris Cohan, Ph.D.Dept. of Pathology/Anat SciJacobs School of Medicine

Overview3. Basal Ganglia interconnected by excitatory and inhibitory

synapses. • increase precision of circuit• makes them difficult to analyze

4. Basal Ganglia diseases upset the balance of excitation and inhibition, leading to 2 paradoxical symptoms:

• Difficulty starting movements• Spontaneous movements at rest

Consequences of UMN needing a boost!

What is Function

• Start• Move• Coordinate• Adjust• Maintain balance and posture

FUNCTION COMPONENT DEFICITS

Start Basal Ganglia Spontaneous Movements

Move Cerebral CortexBrainstem, Sp cord

Weak/Paralyzed

Plan Cerebellum Ataxia

Adjust Cerebellum Ataxia

Balance/EyeMove Cerebellum Falling/nystagmus

Basal Ganglia- How it WorksUMN

Cerebral Cortex

Basal Ganglia

Cerebellum

Brainstem

Spinal Cord

Thalamus

head muscles

body muscles

Booster

The Basal Ganglia FACILITATE

movement

Terminology• Extrapyramidal (ie not the pyramidal system)

• Basal Ganglia are NUCLEI

• Basal Ganglia diseases are called MOVEMENT DISORDERS

Components

1. Caudate2. Putamen3. Globus Pallidus4. Substantia Nigra5. Subthalamic Nucleus

}Striatum

caudate

Subst nigra

GP

putamen

subthalamic nuc- part of diencephalon

3D ShapesCaudate

+

Putamen

Pathway Summary

A loop from cortex to basal ganglia to cortex

VL

corticospinal corticobulbar

putamen

GP

GPeGPi

Output of Basal Ganglia

Lenticular Fasciculus

Thalamic Fasciculus

VL

Pathway Function

VL

CST CBT

VL activity UMN Movementoff off offon on on

putamen

GP

Subthalamic nuc

on

Basal ganglia control the activity of VL.

no effect

Pathway Function

VL

CST CBT

VL activity UMN Movementoff off offon on on

putamen

GP

Subthalamic nuc

What if there was a lesion in the BG that resulted in the switch being permanently turned on!

Lesions of BG components disturb a very sensitive circuit that causes VL to be ON continuously = continuous movement.

on

Direct and Indirect Circuits

VL

STN

indirect circuit

direct circuit

BG utilize a direct and indirect circuit to control VL.

Subthalamic nucleus is involved in the indirect circuit.

Direct and Indirect Circuits

VL

STN

indirect circuit

direct circuit

Direct and indirect circuits have competing effects on GPi to control VL activity.

accelerator

brake

Accelerator – increases VL activityBrake – decreases VL activity

Direct and Indirect Circuits

VL

STN

indirect circuit

direct circuit

When movement is desired, the competing effects of these circuits are resolved by help from substantia nigra. accelerator

brake

Role of Substantia Nigra

Substantia Nigra• pars compacta releases dopamine into putamen• dopamine binds to 2 different receptors on putamen neurons:

SNcdopamine

unstained

SN

putamen

D2 receptors cause inhibition

D1 receptors cause excitation

VL

STN

accelerator

brake

Circuit Summary

The thought to move initiates a small amount of activity in cortical motor areas. Axons from cortex excite putamen neurons. Simultaneously, SN releases dopamine into putamen, which increases the effect of the accelerator and removes the brake. VL activity increases and its axons further excite cortical motor areas where CST/CBT neurons now have enough activity to cause movement.

SNc

dopamineVL

STN

accelerator

brake

CST CBT

SNc

Circuit Details

VL

STN

accelerator

brake

Disinhibition – the tonic inhibition of VL by GPi is stopped when Gpi activity is inhibited by putamen neurons in the direct circuit.

tonic

tonicSNc

SNc

Circuit Details (expanded)

Cortex

VLPutamen

SNc

SNc

GPiD1

D2

STN

GPe

Direct circuit

Indirect circuit

Dopamine • released during initiation of movement• direct circuit: ß GPi, ­ VL • indirect circuit – ß STN, ß GPi, ­ VL

Circuit Details

VL

STN

accelerator

brake

Compared to dopamine, ACh has opposite effects on the direct and indirect circuits. A balance between dopamine and ACh is important for BG function.

tonic

tonicSNc

SNc

ACh

ACh

1. ß Effect of direct pathway

2. ­ Effect of indirect pathway

3. Abnormal rhythmic activity in neurons

Parkinson’s Disease

Slowed movement

Resting Tremor

ß Accelerator

­ Brake

Hypokinetic disorder

VL

STN

accelerator

brake

tonic

tonicSNc

SNc

• SNc degenerates• Dopamine is lost from putamen

X

X

VL

STN

accelerator

brake

tonic

tonicSNc

SNc

• Putamen neurons in indirect circuit degenerate(also caudate nuc)

Huntington’s Disease

chorea

In Huntington’s Disease:

1. ß Effect of indirect pathway ® ß GPi, ­ VL = movementD2R cells ® GPe degenerate

Hyperkinetic disorder

VLaccelerator

brake

tonic

tonic

STN

SNc

SNc

Degeneration of STN

Hemiballismus

Occurs from a lesion of STN

• effects are similar to Huntington’s except more violent

• ß Effect of indirect pathway ® ß GPi, ­ VL = movement

Hyperkinetic disorder

XX

VLaccelerator

brake

tonic

tonic

STN

SNc

SNc

SUMMARY

Lesions in Huntington’s, Hemiballismus increase VL activity by removing the brake.

Lesion in PD decreases presence of dopamine, causing the accelerator and brake circuits to compete and result in difficulty starting movement.

Symptoms of BG Disease1. Involuntary movements (dyskinesias)

• hemiballismus• chorea – Huntington’s Disease• dystonia/athetosis• resting tremor – Parkinson’s Disease

2. Decreased voluntary movement• Hypokinesia / Bradykinesia

3. Change in posture/muscle tone• Rigidity – lead pipe with cogwheeling

An increase in muscletone different from

spasticity

Increased muscle tone in both flexors and extensors

superimposed tremor

Blood Supply

Putamen and Globus Pallidus are supplied by branches of the middle cerebral artery. Occlusion of these branches can cause BG symptoms.

Basal Ganglia Diseases (movement disorders)Disease Lesion Site Symptoms

Ballism STN Wild,flailing movements

Parkinson’smost common movement disorder

SNc Resting tremor, ßmovement, rigidity, altered gait/posture

Huntington’s• autosomal dominant• adult onset

Putamen D2R neurons/Caudate

Chorea; caudate damage causes personality changes and dementia

Tardive dyskinesia Drug-induced block of D2 and other receptors

(eg antipsychotics)

Facial chorea/athetosis

Tourettes’s unknown Motor and verbal tics

.

PD Treatments1. Dopaminergic Drugs –

2. Pallidotomy – surgical lesion of GPi• reduces inhibition of VL• irreversible• danger of lesion in nearby internal capsule

3. Deep Brain Stimulation – implant stimulator into Gpi, STN

4. Implant dopamine secreting cells into BG - abandoned in 2003, but new trial underway using stem cells.

­L-Dopa; ßdopamine metabolism

• STN stim gives best result; stim inhibits STN!• best effect: reducing tremor

Meds for other symptoms• non-damaging, reversible, adjustable procedure!

Motor Loop

Cortical motor areas

Globus Pallidusi/SN

VL of thalamus

Putamen

Basal Ganglia have Other Functions

Cognitive/Emotional LoopPrefrontal Cortex

VA of thalamus

Globus Pallidusi/SN

Caudate

Basal Ganglia diseases eventually involve cognitive and emotional deficits in addition to motor deficits. The former arise from connections with prefrontal cortex (PFC):

dorsolateral PFC – working memory, executive functions

orbitomedial PFC– emotion and motivation

1. Neurotransmitter synthesis

2. Storage in Vesicles

4. Neurotransmitter Release

3. Ca entry

5. Binding to Receptors

6. Degradation in cleft, metabolism, or diffusion

7. Reuptake transporter

9. Modulation by presynaptic receptors

Postsynaptic membrane

G

8. Recycling vesicles

Review catecholamine synthesis and metabolism pathway to understand Silvestri lecture.

Levodopa, MAO inhib

Agonists

COMT inhibitors

Amantadine?