Basal Ganglia Ppt

Basal Ganglia

Direct and Indirect Pathways and Connections

Mary K. Vaughan, Ph.D.

Basal Ganglia Game Plan

Neostriatum a.k.a. Striatum

Dorsal component of neostriatum

Caudate nucleus Putamen

Ventral component of striatum

Nucleus accumbens**Olfactory tubercle -

Important in Limbic Loop in phase 3

Somatotopy of Inputs to the Caudate and Putamen

Head of the caudate Frontal eye fields and prefrontal cortex

Dorsal PutamenInput from leg area of cortex

Ventral putamenInput from face and hand area of cortex

PaleostriatumConsists of two subnuclei

globus pallidus interna (Gpi)globus pallidus externa (Gpe)

GPe

GPi

Substantia nigraFound in the mesencephalonConsists of two subnuclei

substantia nigra pars compacta (SNpc)substantia nigra pars reticulata (SNpr)

Substantia nigra

Subthalamic nucleus

Subthalamic nucleus

Four Nuclei of Basal GangliaCaudate/putamenGlobus pallidus

GPiGPe

Substantia nigrapars compacta (SNpc)pars reticulata (SNpr)

Subthalamic nucleus

Ansa lenticularis

Ansa lenticularis exits from the globus pallidus interna (Gpi), comes around the internal capsule and joins other tracts of the thalamic fasciculus

Lenticular Fasciculus

Lenticular fasciculus exits from Gpi and forms part of the border of the subthalamic nucleus

Joins other tracts in thalamic fasciculus

Thalamic FasciculusA collection of tracts that are destined for the VL and some for the VA as well.

Composed of the:Lenticular fasciculusAnsa lenticularisNigrothalamic tractDentatothalamic tract from cerebellum

Subthalamic Fasciculus

A loop connectingGPe with STN via GABAergic pallido-subthalmic projections

Subthalamic nucleus projects back to the GPi via subthalamo-pallidal excitatory glutaminergic projections

Output Thalamic Nuclei

Part of the basal ganglia output back to the cortex

Output thalamic nuclei

Part of thalamic output back to the cortex

Other output to nuclei of the brain stem

Pedunculopontine nuclei – a nucleus of the old motor system in the locomotor area of the reticular formation

Tectum, particularly superior colliculus

Parallel Circuits in Basal Ganglia

Information flow through the basal ganglia is separated into five distinct parallel circuits each with its own direct and indirect pathway.

Motor loopOculomotor loopDorsolateral prefrontal loopLateral orbitofrontal loopLimbic loop

Today

Phase 3

Loops of the Basal GangliaEach loop

Starts from specific areas of cortexPasses through distinct regions of the basal gangliaModulates different areas of the thalamusReturns to distinct cortical regions that requested the information

Motor Loop

Starts in supplementary motor cortex, primary motor and premotor corticesProjects mainly to putamenProjections to thalamus include

VLoVACM

CM

DeLong’s Direct and Indirect Pathways

He proposed that basal ganglia output can be grouped into two projection systems

Direct pathwayIndirect pathway

It has been proposed that the basal ganglia are parallel processing information

They appear to function in “balanced opposition”

Neurotransmitters

GABA – inhibitoryGlutamate – StimulatoryAcetylcholine – within neostriatumNeuropeptides – co-localized with GABA

EnkephalinSubstance P/dynorphin

DopamineD1 – stimulates adenylate cyclase activityD2 – inhibits adenylate cyclase activity

Striatal Cholinergic Interneurons

Cholinergic interneurons in the striatum are stimulatory particularly in the indirect pathway

Centrally active anticholinergic, antiparkinsonian drugs act via muscarinic receptors and reduce activity of striatal cholinergic interneurons

Striatal cholinergic interneurons

Direct Pathway

Glu (Stimulation)GABA (Inhibition)GABA (Inhibition)Glu (Stimulation)

Indirect Pathway

GluGABAGABAGluGABAGlu

Parkinson’s Disease

BradykinesiaPill-rolling tremorMasked faciesMicrographiaMicrophoniaMarche de petit pasPostural InstabilityAutonomic dysfunctionFestinating gaitSeborrheaCramps of feet or toesDecreased eyeblink

Signs and Symptoms

BradykinesiaSlow and small stepsMasked facies (little movement, staring)Small handwriting

Resting tremor (pill rolling tremor)Postural instabilityRigidity

Pathology in Parkinson’s Disease

Loss of dopamine containing neurons in the pars compacta of substantia nigra

Depletion of dopamine in striatum which correlates with severity of dopamine cell loss in the SNpc at post-mortem

Progressive Stages

MPTP

N-methyl-2,3,4,6-tetrahydropyridine is a dopamine neurotoxin that selectively destroys SNpc neurons

Produces Parkinson’s disease in man and primates

Causes loss of dopamine in striatum

Drug-Induced Parkinson’s Disease

Drugs that deplete brain dopamine e.g., reserpine

Drugs that block dopamine receptors e.g., phenothiazine and butyrophenoneantipsychotic drugs

Reversible upon drug elimination

Huntington’s Disease

DementiaHyperactivity

Huntington’s Disease

Autosomal dominant

Caused by an abnormal CAG repeat

Normal 11-34Abnormal 38-121

Caudate nucleus dies

Progressive dementia

Usually manifested in the 40’s

Genetic test now available

Hemiballism

Discrete unilateral lesion of the subthalamic nucleus

Forceful, violent and persistent hyperkinetic movements

Involves the contralateral limbs and mainly the proximal musculature

Wilson’s disease Hepatolenticular degeneration

Autosomal recessive disorder of chromosome 13Onset usually 13-25 yearsAccumulation of copper in liverKayser-Fleischer rings in eye due to CuPutamen degenerates

Sydenham’s choreaAn autoimmune disease caused by rheumatic feverChorea may last 3-6 weeksUsually seen in childrenAlso called St. Vitus dance

Take home message

Alterations in output via the indirect striatal projection systems is the key to understanding the different basal ganglia disorders.

Decrease activity of STN neuronsdirect lesion - hemiballismincreased inhibition - Huntington’s chorea

Increase activity of STN neuronsIncrease activity of STN neurons - Parkinson’s disease