NSCI 324* Systems Neuroscience

NSCI 324*Systems Neuroscience

Doug MunozCentre for Neuroscience StudiesBotterell Hall, room 226x32111doug.munoz@queensu.ca

Tutorial: Monday Jan 23, 2012 10:30amBotterell B147TA: Jay Jantz (j.jantz@queensu.ca)

NSCI 324*Systems Neuroscience

Vision and Oculomotor Control (Dr. Munoz)January 10 The retina January 13 Central Visual PathwaysJanuary 16 Dr. Munoz Tutorial: January 16 Higher Visual functions January 17 Oculomotor System I. Basic organization January 20 Oculomotor System II. Vestibulo-ocular reflexJanuary 23 Dr. Munoz tutorial:January 23 Oculomotor System III. SaccadesJanuary 24 Basal Ganglia for cognitive and motor controlJanuary 27 review of Dr. Munoz lecture materialJanuary 30 Dr. Munoz exam in tutorial period

Basal Ganglia

Basal Ganglia• Collection of nuclei deep in telencephalon, diencephalon, and midbrain

• Play a very important role in cognition and motor control

Basal Ganglia• Caudate Nucleus (CN)

Basal Ganglia• Caudate Nucleus (CN)• Putamen (P)

} Striatum

Basal Ganglia• Caudate Nucleus (CN)• Putamen (P)• Globus pallidus (GP)

} Lentiform nucleus

Basal Ganglia• Caudate Nucleus (CN)• Putamen (P)• Globus pallidus (GP)

•external segment (GPe)•Internal segment (GPi)

Basal Ganglia• Caudate Nucleus (CN)• Putamen (P)• Globus pallidus (GP)

•external segment (GPe)•Internal segment (GPi)

• Sustantia nigra (SN)•pars reticulata (SNpr)•pars compacta (SNpc)

Basal Ganglia• Caudate Nucleus (CN)• Putamen (P)• Globus pallidus (GP)

•external segment (GPe)•Internal segment (GPi)

• Sustantia nigra (SN)•pars reticulata (SNpr)•pars compacta (SNpc)

BG Output

Basal Ganglia• Caudate Nucleus (CN)• Putamen (P) •Globus pallidus (GP)•external segment (GPe)•Internal segment (GPi)• Sustantia nigra (SN)•pars reticulata (SNpr)•pars compacta (SNpc)• Subthalamic nucleus (STN)

•

Basal Ganglia• Caudate Nucleus (CN)• Putamen (P)• Globus pallidus (GP)

•external segment (GPe)•Internal segment (GPi)

• Sustantia nigra (SN)•pars reticulata (SNpr)•pars compacta (SNpc)•Subthalamic nucleus (STN)

} Striatum

BG Output

} Lentiform nucleus

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

Simplified Basal Ganglia Circuit

GLU

GLU

GABA

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

Simplified Basal Ganglia Circuit

GLU

GLU

GABASubstanceP

GABA DIR

ECT

PATH

WA

Y

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

Simplified Basal Ganglia Circuit

GLU

GLU

GLUGABA

GABA

GABA

Enkephalin

IND

IREC

TPA

THW

AY

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

Simplified Basal Ganglia Circuit

GLU

GLU

GABASubstanceP

GLU

GABA

GABA

GABA

Enkephalin

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

Simplified Basal Ganglia Circuit

GLU

GLU

GABASubstanceP

GLU

GABA

GABA

GABA

Enkephalin

GLU

HYPERDIRECTPATHWAY

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

Simplified Basal Ganglia Circuit

GLU

GLU

GABA

DA

GLU

GABA

GABA

GABA

D2

D1

DA-D1: increase excitability in DIRECT pathwayDA-D2: decrease excitability in INDIRECT pathway

Channels through Basal Ganglia

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

Simplified Basal Ganglia Circuit

GLU

GLU

GABA

DA

GLU

GABA

GABA

GABA

D2

D1

Parkinson’s Disease

• progressive degenerative disorder

• degeneration in substantia nigra pars compacta

• leads to reduced dopamine release in striatum (caudate and putamen)

• affects motor function

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

Parkinson’s Disease: Loss of DA from SNpc

GLU

GLU

GABA

DA

GLU

GABA

GABA

GABA

D2

D1

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

Parkinson’s Disease: Loss of DA from SNpc

GLU

GLU

GABA

DA

GLU

GABA

GABA

GABA

D2

D1

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

Parkinson’s Disease: Loss of DA from SNpc

GLU

GLU

GABA

DA

GLU

GABA

GABA

GABA

D2

D1

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

Parkinson’s Disease: Loss of DA from SNpc

GLU

GLU

GABA

DA

GLU

GABA

GABA

GABA

D2

D1

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

Parkinson’s Disease: Loss of DA from SNpc

GLU

GLU

GABA

DA

GLU

GABA

GABA

GABA

D2

D1

Leads to reduced excitability in cortexinability to initiate movement

Parkinson’s Disease

What Causes Parkinson’s Disease?

Exogenous toxins Oxidative stress Genetic Predisposition Infection Drug-induced

loss of DA neurons in SNpc

100

Viab

le D

A N

euro

ns (%

)

Age (yrs)100

20-25Threshold for diagnosis

Loss of DA neurons leads to Parkinson’s

PD at 95+PD at 50+

100

Viab

le D

A N

euro

ns (%

)

Age (yrs)100

20-25Threshold for diagnosis

Loss of DA neurons leads to Parkinson’s

PD at 95+PD at 55+

Sudden Insult

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

Parkinson’s Disease: Loss of DA from SNpc

GLU

GLU

GABA

DA

GLU

GABA

GABA

GABA

D2

D1

Leads to reduced excitability in cortexinability to initiate movement

Huntington’s Disease

•Inhereted (genetic) disorder that manifests in midlife

•Autosomal dominant trait

•Restlessness and choreiform (rapid, jerky) movements in arms and face

•Starts with degeneration in Indirect pathway

•Degeneration spreads through basal ganglia

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

GLU

GLU

GABA

DA

GLU

GABA

GABA

GABA

D2

D1

Simplified Basal Ganglia Circuit

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

GLU

GLU

GABA

DA

GLU

GABA

GABA

GABA

D2

D1

Huntington’s Disease: Degeneration in Basal Ganglia

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

GLU

GLU

GABA

DA

GLU

GABA

GABA

GABA

D2

D1

Huntington’s Disease: Degeneration in Basal Ganglia

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

GLU

GLU

GABA

DA

GLU

GABA

GABA

GABA

D2

D1

Huntington’s Disease: Degeneration in Basal Ganglia

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

GLU

GLU

GABA

DA

GLU

GABA

GABA

GABA

D2

D1

Huntington’s Disease: Degeneration in Basal Ganglia

Cortex

CaudatePutamen GPe

SNrGPi STNThalamus

SNpc

GLU

GLU

GABA

DA

GLU

GABA

GABA

GABA

D2

D1

Huntington’s Disease: Degeneration in Basal Ganglia

Leads to increased excitability in cortexinability to inhibit movement