Cindy Montana's Neuro Exam 2 Review

By Cindy Montana

WUMS I Neuroscience2006

Pathways

Brainstem Atlas

Brainstem Syndromes

Somatosensory

Pain

Motor

Autonomic Nervous System

Oculomotor / Oculodominance

Hypothalamus

Limbic

Sleep

Memory

Language

References

Note: If a slide says CLICK, click outside the buttons to advance the animation until CLICK disappears. Otherwise, use the arrow buttons (top right) to navigate between slides.

Pathways

• Fine Touch• Pain/Temperature• Proprioception• Corticospinal/Corticobulbar• Rubrospinal/Tectospinal• Reticulospinal• Vestibulospinal

MAIN

Spinal Cord

C

gracile fasciculus

cuneate fasciculus

dorsalcolumns

sacrallumbarthoraciccervical

afferent Aβ fiber1st order

SLT

dorsal rootganglion

FINE TOUCH

Aβ fibers (large) enter the spinal cord medial to Aδ, C fibers (small)

CLICK

MAIN SECTION

Medullagracile nucleus

cuneate nucleus

mediallemniscus2nd order


CROSS

internalarcuate

fibers2nd order

FINE TOUCH

CLICK

MAIN SECTION

Pons

trigeminal main sensory nucleus

trigeminal ganglion

trigeminal motor nucleus

medial lemniscus2nd order

sacrallumbarthoraciccervicaltrigeminal – sensory

FINE TOUCH

CLICK

MAIN SECTION

Midbrain


inferiorcolliculus

lateral lemniscus


FINE TOUCH

CLICK

MAIN SECTION

Midbrainsuperior

colliculus

red nucleus



laterallemniscus

FINE TOUCH

CLICK

MAIN SECTION

Forebrain


VPM*

VPL*

internal capsule3rd order

click here for horizontal section

primary somato-sensory cortex

click here

FINE TOUCH

CLICK

MAIN SECTION

* These nuclei are slightly displaced in this view, to illustrate that trigeminal input VPM and body input VPL

Internal Capsule – Horizontal Section

anterior limb

posterior limb


genu

MAIN SECTION

Spinal Cord


SL

dorsal rootganglion

Aδ fiber1st order

C fiber1st order

interneuron

Lissauer’s tract

substantia gelatinosa (RL II)

nucleus proprius(RL III, IV)

CROSS

2nd order tracts:spinothalamic/spinoreticular/spinomesencephalic

anterior white commissure2nd order

TC

PAIN/TEMP

Aδ, C fibers (small) enter the spinal cord lateral to Aα fibers (large)

posterior marginalis (RL I)

CLICK

MAIN SECTION

RL = Rexed lamina

Medulla


trigeminalafferent1st order

trigeminalspinal tract

1st order

trigeminalspinal nucleus CROSS

PAIN/TEMP

2nd order tracts:spinothalamic/spinoreticular/spinomesencephalic

medullary reticularformation

CLICK Show Spinoreticular Tract

MAIN SECTION

Pons

trigeminal ganglion

trigeminalafferent1st order

[to medulla]


trigeminal spinal tract

1st order

spinothalamic, spinomesenephalictracts2nd order

PAIN/TEMP

pontine reticularformation

CLICK Show Spinoreticular Tract

MAIN SECTION

Midbrain

spinothalamic/spinomesen-cephalic tracts2nd order


inferiorcolliculus

mediallemniscus

PAIN/TEMP

CLICK

MAIN SECTION

Midbrainsuperior

colliculus

red nucleus


mediallemniscus

spinothalamic tract2nd order

PAIN/TEMP

periaqueductal gray (PAG)

mesencephalicreticularformation

CLICK Show Spinomesencepahalic

Tract

MAIN SECTION

Forebrain


VPM*

VPL*

internal capsule(posterior limb)

3rd order

PAIN/TEMP

Spinothalamic tract (no evidence for orderly topographic cortical map)

primary somato-sensory cortex

click here

CLICK

MAIN SECTION

* These nuclei are slightly displaced in this view, to illustrate that trigeminal input VPM and body input VPL

Spinal Cord - SacralPROPRIOCEPTION

dorsal rootganglion dorsal columns

Aα fibers (large) enter the spinal cord medial to Aδ, C fibers (small)

afferent Aα fiber1st order

CLICK

MAIN SECTION

Spinal Cord - Thoracic

Clarke’s nucleus(dorsal nucleus)

T1-L2

dorsalspinocerebellar

tract2nd order

PROPRIOCEPTION

CLICK

MAIN SECTION

Spinal Cord - Cervical

dorsal rootganglion

dorsal columns


tract2nd order

PROPRIOCEPTION

afferent Aα fiber1st order

CLICK

MAIN SECTION

Medulla


tract2nd order

cuneocerebellar tract2nd order

external (accessory)cuneate nucleus

PROPRIOCEPTION

CLICK

MAIN SECTION

Medullainferior

cerebellar peduncle2nd order

PROPRIOCEPTION

CLICK

MAIN SECTION

Cerebellum

deep cerebellar nuclei (see right)

medial (fastigius)

interposed (globose + emboliform)

lateral (dentate)

mossy fibers

inferior cerebellarpeduncle (restiform body)

PROPRIOCEPTION

CLICK

MAIN SECTION

Pons

trigeminal ganglion

efferent α-MN in CN V3(to masseter, temporalis)

mesencephalic ganglion

trigeminal motor nucleus

afferent Aα fiber(from masseter, temporalis)

PROPRIOCEPTIONCLICK

MAIN SECTION

Forebrain

internal capsule(posterior limb)

Precentral, prefrontal, postcentral gyri

cerebral peduncle

to lumbar spinal cordto cervical spinal cordto CN motor nuclei

CORTICOSPINAL/CORTICOBULBAR

corona radiata

CLICK

MAIN SECTION

Midbrain


cerebral peduncle

superiorcolliculus

red nucleus

oculomotor nucleus


CLICK

MAIN SECTION

Midbrain

trochlear nucleus

inferiorcolliculus

cerebral peduncle



CLICK

MAIN SECTION

Pons

corticospinal tract

middle cerebellar peduncle

trigeminal (CN V) motor nucleus



CLICK

MAIN SECTION

Ponsabducens (CN VI)

nucleus

facial (CN VII) nucleus

This nucleus is complicated – click here corticospinal

tract




CLICK

MAIN SECTION

Medullahypoglossal (CN XII)

nucleus

nucleus ambiguous

corticospinal tract



CLICK

MAIN SECTION

Medulla

CROSS

trigeminal (CN V) spinal nucleus

pyramidal decussation

pyramidto lumbar spinal cordto cervical spinal cord


CLICK

MAIN SECTION


ventral horn

lateral corticospinal

tract

anterior corticospinal tract

to lumbar spinal cordto cervical spinal cord

ventral white commissure

PF DF

PE DE Regions of the ventral horn that innervate…- proximal flexors = PF- distal flexors = DF- proximal extensors = PE- distal extensors = DE


CLICK

MAIN SECTION

CROSS


to lumbar spinal cord


tract



CLICK

MAIN SECTION

Spinal Cord - Sacral


tract


ventral horn

to lumbar spinal cord

ventral white commissure


CLICK

MAIN SECTION

CROSS

Midbrain

rubrospinaltectospinal

superior colliculus

red nucleus

RUBROSPINAL/TECTOSPINAL

dorsal tegmental decussation

ventral tegmental decussation

input from forebrainCLICK

MAIN SECTION

Ponstectospinal tract

pontine reticular formation

rubrospinal tract



CLICK

MAIN SECTION

Medullatectospinal tract

rubrospinal tract

medullary reticular formation

MLF



CLICK

MAIN SECTION

Medulla

tectospinal tract

rubrospinal tract

trigeminal (CN V) spinal nucleus

pyramidal decussation

pyramidrubrospinaltectospinal


CLICK

MAIN SECTION



tectospinal tract

rubrospinal tract

ventral horn


CLICK

MAIN SECTION

Spinal Cord - Lumbar

rubrospinal

rubrospinal tract

ventral horn


CLICK

MAIN SECTION

Pons

medial reticulospinal tractlateral reticulospinal tract

pontine reticular formation

medial longitudinal fasciculus (MLF)

RETICULOSPINALCLICK

MAIN SECTION

MedullaMLF


RETICULOSPINALCLICK

MAIN SECTION

Medulla

MLF


RETICULOSPINALCLICK

MAIN SECTION



RETICULOSPINALCLICK

MAIN SECTION



RETICULOSPINALCLICK

MAIN SECTION



RETICULOSPINALCLICK

MAIN SECTION

Ponslateral vestibular

nucleus

medial vestibular nucleus

medial longitudinal fasciculus (MLF)

medial vestibulospinal tractlateral vestibulospinal tract

VESTIBULOSPINALCLICK

MAIN SECTION

Medulla


MLF


MAIN SECTION




MAIN SECTION


lateral vestibulospinal tract


MAIN SECTION


lateral vestibulospinal tract


MAIN SECTION

Brainstem Atlas

• Open Medulla• Lower Pons• Middle Pons• Upper Pons• Midbrain

MAIN

Open MedullaCN XII nucleus

medial longitudinal fasciculus

medial lemniscus

inferior olivary fibers

pyramids

dorsal motor nucleus of the vagus


nucleus of the solitary tract

solitary tract

spinal trigeminal tract

spinal trigeminal nucleus

nucleus ambiguus

inferior olivary nucleus

inferior cerebellar peduncle

nucleus raphe magnus

Medial Syndrome

Lateral Syndrome

MAIN SECTION

Lower PonsCN VI nucleus

medial longitudinal fasciculusmedial

lemniscus

pontine fibers

corticospinal tract

CN VII motor nucleus


lateral vestibular nucleus

superior olivary nuclear complex

pontine nuclei


lateral lemniscus

spinothalamic tract

raphe nuclei

Medial Syndrome

Lateral Syndrome

MAIN SECTION

Middle PonsCN V main sensory nucleus

CN V motor nucleus

lateral lemniscus

CN V mesencephalic nucleus

CN V mesencephalic tract

Medial Syndrome

Lateral Syndrome

MAIN SECTION

Upper Pons

central tegmental bundle


medial lemniscus

corticospinal tract

pontocerebellar fibers

locus coeruleus

parabrachial region

periaqueductal gray

Medial Syndrome

Lateral Syndrome

MAIN SECTION

Midbrain

medial lemniscus

superior cerebellar peduncle

red nucleus

CN III

cerebral peduncle

superior [inferior is caudal] colliculusperiaqueductal gray

Click here to expand this region

Tegemental Syndrome

Ventral Syndrome

MAIN SECTION

Brainstem Syndromes

• Medial Medullary• Lateral Medullary• Medial Inferior Pontine• Lateral Inferior Pontine• Medial Mid-Pontine• Lateral Mid-Pontine• Medial Superior Pontine• Lateral Superior Pontine• Tegmental• Ventral

MAIN

Medial Medullary Syndrome

ARTERY: anterior spinal artery

Loss of vestibuloocular reflex*Tongue paralysisLoss of fine touch (contralateral)Cerebellar ataxiaLimb paralysis (contralateral)

CN XII nucleus


medial lemniscus

inferior olivary fibers

pyramids

MAIN SECTION

* VOR might be preserved because this is below the level of the vestibular nuclei

Lateral Medullary Syndrome

ARTERY: posterior inferior cerebellar artery (PICA)

Loss of facial pain/temp sensation (ipsilateral)Hoarseness, difficulty swallowingHorner’s syndrome, ipsilateral loss of sweatingCerebellar ataxiaLoss of body pain/temp sensation (contralateral)

nucleus ambiguus

CN V spinal nucleus

descending symapthetic

tract

dorsal spinocerebellar

tract

spinothalamic tract

MAIN SECTION

Medial Inferior Pontine Syndrome

ARTERY: paramedian branches of the basilar artery

Loss of vestibuloocular reflexLoss of lateral rectus (ipsilateral)Loss of fine touch (contralateral)Cerebellar ataxiaLimb paralysis (contralateral)

CN VI nucleus

medial longitudinal fasciculusmedial

lemniscus

pontine fibers

corticospinal tract

MAIN SECTION

Lateral Inferior Pontine Syndrome

ARTERY: anterior inferior cerebellar artery (AICA)

Loss of facial pain/temp sensation (ipsilateral)Loss of body pain/temp sensation (contralateral)Hearing deficit (ipsilateral), vertigoFacial paralysis (ipsilateral)

spinothalamic tract

CN V spinal nucleus

CN VIII

CN VII

MAIN SECTION

Medial Mid-Pontine Syndrome

ARTERY: paramedian branches of the basilar artery

Limb paralysis (contralateral)Facial paralysisCerebellar ataxia

corticobulbar tract

corticospinal tract

corticopontine/ pontocerebellar

fibers

MAIN SECTION

Lateral Mid-Pontine Syndrome

ARTERY: circumferential branches of the basilar artery

Weakened masticationLoss of facial sensation (ipsilateral)No deficit reported

CN V main sensory nucleus

CN V motor nucleus

lateral lemniscus

MAIN SECTION

Medial Superior Pontine Syndrome

ARTERY: paramedian branches of the upper basilar artery

Loss of vestibuloocular reflexSoft palate temorLoss of fine touch (contralateral)Limb paralysis (contralateral)Cerebellar ataxia

central tegmental bundle


medial lemniscus

corticospinal tract


MAIN SECTION

Lateral Superior Pontine Syndrome

ARTERY: superior cerebellar artery

Cerebellar ataxiaLoss of body pain/temp sensation (contralateral)Loss of fine touch (contralateral)

spinothalamic tract


medial lemniscus


MAIN SECTION

Tegmental Syndrome

ARTERY: paramedian branches of the basilar a. / posterior cerebral a.

Cerebellar ataxiaLoss of fine touch to body and face (contralateral)No deficit reportedLoss of pupil constriction; lateral strabismus

medial lemniscus


red nucleus

CN III

MAIN SECTION

Ventral Syndrome

ARTERY: paramedian branches of the basilar a. / posterior cerebral a.

Paralysis (contralateral)Loss of pupil constriction; lateral strabismus

cerebral peduncle

CN III

MAIN SECTION

Somatosensory

• Ascending Somatic Pathways– Fine Touch– Pain/Temperature– Proprioception

• Lesions– Peripheral– Spinal Cord– Forebrain

• Peripheral Receptors• Somatosensory Cortex• Somatosensory Plasticity

MAIN

Lesions - Peripheral

Lesion location Sensory loss DistributionPeripheral nerve All sensation Distribution of the nerve

Peripheral neuropathy Large myelinated fibers first

Bilateral, “stocking-glove”

Single dorsal root None

Several dorsal roots All Ipsilateral dermatomal (fine touch less affected than pain/temp)

MAIN SECTION

Lesions - Spinal Cord

Lesion location Sensory loss DistributionCentral cord, early Pain/temp Bilateral, at level of lesion

Dorsal column Fine touch, position Ipsilateral, from lesion on down

Anterolateral column Pain/temp Contralateral, from lesion on down

Hemi-transection of cord Fine touch, positionPain/temp

Ipsilateral, lesion on downContralat., lesion on down

Complete cord transection

All sensation Lesion on down

MAIN SECTION

Lesions - Forebrain

Lesion location Sensory loss DistributionThalamus All sensation Contralateral (peri-oral

facial sparing from ipsi fibers)

Cortex Varies by location of lesion

Contralateral

MAIN SECTION

Peripheral Receptors

Merkel’s disk

Meissner’s corpuscle

Pacinian corpuscle

Ruffini ending

Dermis

Epidermis

Click on a receptor:

free nerve ending

MAIN SECTION

Merkel’s DiskDiscriminative Touch Mechanoreceptor

Location: EpidermisSpecificity: Steady skin indentation – form, textureDynamics: Slow-adaptingSpatial Range: Small receptive field (3-4 mm fingers, 30-40 cm trunk)

2-point discrimination threshold = 1 mm fingers, 10 cm trunkConduction: Aδ fiber – 25 m/s

MAIN SECTION RECEPTORS

Location: DermisSpecificity: Flutter; contact and movementDynamics: Fast-adaptingSpatial Range: Small receptive field (3-4 mm fingers, 30-40 cm trunk)

2-point discrimination threshold = 1 mm fingers, 10 cm trunkConduction: Aδ fiber – 25 m/s

Meissner’s CorpuscleDiscriminative Touch Mechanoreceptor


Location: Subcutaneous tissueSpecificity: Non-localized vibrationDynamics: Fast-adaptingSpatial Range: Large receptive fieldConduction: Aδ fiber – 25 m/s

Pacinian CorpuscleDiscriminative Touch Mechanoreceptor


Location: DermisSpecificity: Low frequency stimulationDynamics: Slow-adaptingSpatial Range: Large receptive fieldConduction: Aδ fiber – 25 m/s

Ruffini EndingDiscriminative Touch Mechanoreceptor


Free Nerve EndingPain/Temperature Receptor

Aδ C

Specificity Cold or fast pain Warmth or slow pain

Conduction 25 m/s (myelinated) <1 m/s (unmyelinated axon, 1-2 um diameter)


Somatosensory Cortex

4

3a

3b

1

2

5

7

lateral sulcus

central sulcus

postcentral gyrus intraparietal sulcus

posteriorparietal lobule central

sulcus postcentral gyrus – S1intraparietalsulcus

posteriorparietal lobule

S2

M1

Click on an area:

Click here for S1 topographyClick here for S1 histology

MAIN SECTION


4

3a

3b

1

2

5

7

lateral sulcus

central sulcus





M1

Click on an area:

S1 – Area 3a• Input from thalamic shell (muscles, joints, deep

mechanoreceptors)• RFs similar to periphery

S2


MAIN SECTION


4

3a

3b

1

2

5

7

lateral sulcus

central sulcus





M1

Click on an area:

S1 – Area 3b• Input from thalamic core (VPM/VPL - cutaneous)• Each column within 3b is specific for one type of

cutaneous receptor• Smallest RFs

S2


MAIN SECTION


4

3a

3b

1

2

5

7

lateral sulcus

central sulcus





M1

Click on an area:

S1 – Area 1• Input from 3b and thalamic core (cutaneous)• Large, complex RFs – combine info from multiple

receptor types• Sensitive to motion, direction, orientation• Primarily tactile info• LESION trouble describing texture

S2


MAIN SECTION


4

3a

3b

1

2

5

7

lateral sulcus

central sulcus





M1

Click on an area:

S1 – Area 2• Input from 3a, 3b and thalamic core (cutaneous) +

shell (muscle)• Large, complex RFs• Combines tactile and muscle info• LESION poor stereognosis, can’t pick up small

objects or maneuver hand through tight places

S2


MAIN SECTION


4

3a

3b

1

2

5

7

lateral sulcus

central sulcus





S2

M1

Click on an area:

S2• Input from S1 and thalamus• Two complete maps• Complex RFs with influence of behavioral state• Collosal connections:

– Bilateral RFs– Interhemispheric transfer of learned info

• LESION problems with tactile discrimination, interhemispheric transfer of learned info


MAIN SECTION


4

3a

3b

1

2

5

7

lateral sulcus

central sulcus





M1

Click on an area:

Area 5• Input from area 2 (S1)• Cutaneous plus movement• Very complex RFs: Multi-joint, multi-limb• Responds differently to active and passive movement

S2


MAIN SECTION


4

3a

3b

1

2

5

7

lateral sulcus

central sulcus





M1

Click on an area:

Area 7• High order visual area• Activity reflects spatial properties of visual stimuli• Large RFs, prominent effects of behavioral relevance

S2


MAIN SECTION

Somatosensory Topography

• Face lies near fingers, not neck and head

• Area devoted to each body part reflects the density of sensory innervation

• Extremely distorted

• All areas of S1 (3a, 3b, 1, 2) have complete maps

• S2 has two complete maps

MAIN SECTION


precentral gyrusMOTOR

postcentral gyrusSENSORY

I

II

III

IV small granule cells

V

VI

MAIN SECTION

Somatosensory Plasticity

• Finger amputated corresponding cortical areas are taken over by adjacent finger representations

• Limb amputated (1) smaller “phantom limb” is perceived; (2) tactile acuity on stump increases, and its stimulation results in sensation on the phantom limb– Possibly due to the stump taking over cortical territory

• Better recovery if nerve is crushed rather than severed/reattached– Regenerating axons might follow their Schwann cell tubes

• Plasticity does not require damageMAIN SECTION

Pain

• Types of Pain– Nociceptive– Inflammatory– Neuropathic

• Central Pain Modulation• Sensitization

– Peripheral– Central

MAIN

Nociceptive Pain

TISSUEINJURY

ACTIVATENOCICEPTORS

Types of Nociceptors

MAIN SECTION

Inflammatory Pain

INSULTINFLAMMATORYMEDIATORS

NOCICEPTORACTIVATION

MAIN SECTION

Neuropathic Pain

REPETITIVE STRESSINJURY (TO NERVES) LESION

PAIN

MAIN SECTION

Types of Nociceptors

• Location: Everywhere but the CNS• Neurotransmitters:

– All are excitatory glutamatergic (AMPA, NMDA, kainate, metabotropic)– Some express peptide NTs like substance P, CGRP, NPY

Nociceptor Responds to…Fiber typeMyelinationConduction

Type of painChannel types(Transduction)

Thermal Extreme temperature (>45oC or < 5oC)

Aδ Light myelin5-30 m/s

Sharp, stinging, well localized

TRP (Transient Receptor Potential)

Mechanical Intense pressure AδLight myelin5-30 m/s

Sharp, stinging, well localized

DEG/ENaC (ASIC - Acid Sensing Ion Channel)Maybe TRP

Polymodal Extreme temperatureIntense pressureNoxious chemicals

C fibersNo myelin1 m/s

Dull aching or burning, prolonged, poorly localized

DEG/ENaC (ASIC)

MAIN SECTION

Central Pain ModulationPAGElectrically stimulate or apply opiates here

nucleus raphe magnus (NRM)

NRM projectionterminus

5-HTinhibits

dorsal horn neuron(ascending pain afferent)

NOTE:1) Dorsal horn neuron also receives

descending pain-facilitation inputs.2) Serotonin has other indirect effects,

involving opiate receptors and enkephalins.

via dorsolateral funiculus

dorsal horn

CLICK

MAIN SECTION

Sensitization - Peripheral

Injury

Release bradykinin, prostaglandins

subs

tance

P

stimulate

mast cell

degranulation

histamine

dorsal horn

dorsal root ganglion

excite

activate/sensitize

Sensitization can occur via:1) Potentiation of sensory transduction channel function2) Enhancement of neuronal excitability

nociceptor /peripheral ending

MAIN SECTION

CLICK

Sensitization - Central

dorsal horn

nociceptorterminus

dorsal hornneuron

Limbic augmentation(anxiety, anticipation, etc.)

PPP

PP

P

Hyperphosphoryl-ation of ion

channels in dorsal horn neurons

Increased excitability of dorsal

horn neurons

Chronic pain

+ Repeated stimulation (e.g., by nociceptors)

....

ion channels

MAIN SECTION

CLICK

Motor

• Motor Pathways• Deficits/Lesions• Motor Cortex• Reflexes• Posture• CN VII• Basal Ganglia• Cerebellum

MAIN

Motor Pathways• Motor input to CN nuclei: Corticobulbar tract

• Lateral descending motor pathway– Corticospinal tract– Control of voluntary limb movements (distal body parts)

• Medial descending motor pathway– Vestibulospinal, tectospinal, reticulospinal tracts– Control of postural movements (proximal body parts)

• Other: – Rubrospinal tract is involved in voluntary limb movements

MAIN SECTION

Motor Deficits

Negative Deficit Positive Deficit

Severing amotor nerve

Weakness or paralysis Fibrillation (spontaneous firing of single muscle fibers)

Disease ofmotor neurons

Weakness or paralysisFasciculation (spontaneous firing of an axon twitch of all fibers in the motor unit)

Damage to the descending pathways

MAIN SECTION

Damage to Descending Pathways• Effect on stretch reflexes

– Autonomous and overactive (exaggerated)– Claspknife reaction

• Passively extend limb spindle stretch-induced contraction (resistance) activate GTO sudden relaxation

– Clonus• Rhythmic contraction-relaxation tremor• Occurs when you suddenly stretch a muscle and hold at a longer length• Due to cyclic alternations of stretch reflex, GTO, and Renshaw inhibition

• Effect on pain-sensing reflexes– Flexor spasms

• Extreme maintained flexion of leg at foot, knee, and hip• Due to hyperactive pain reflexes

– Babinski response• Big toe moves up when sole of foot is sharply stimulated• Normal in infants• In adults, is the first sign of hyperactive pain reflexes

MAIN SECTION

Cortical Regions

prefrontal cortex

PMA SMA

M1 (Area 4) central sulcus

S1

Area 6

Area 5

Area 7

posterior parietal cortex

Primary motor cortex

PMA = premotor areaSMA = supplementary motor area

Somatosensory cortical areas

Secondary motor cortical areas

Click:

MAIN SECTION

Primary Motor Cortex (M1)• Motor cortical neurons fire to cause voluntary movement (via corticospinal/

corticobulbar pathways)– Lesions in this pathway (prior to synapse in the spinal cord ventral horn) result in

“upper motor neuron” deficits• Impaired movement at individual joints• Weakness• Increased sensitivity and magnitude of spinal reflexes (stretch & nociceptive)

– Irritation in the cortex can cause seizures• Focal (face or arm or leg) or “marching” (face arm leg)

• Columnar organization– Different neurons code for muscle force, joint position, movement direction

• Specialty: Moving single digits – must actively hold other digits (digits 3, 4, 5 have individual tendons but just one muscle)

• Access M1 by conscious thought over pathways from frontal and parietal cortex

M1 topography M1 histology

MAIN SECTION CORTEX

Motor Cortex Topography

• Distal body parts have greater representation than proximal body parts

• Map is over-detailed – in reality, cortical lesions affect entire body regions (face, arm, leg) and not smaller parts

• Corticospinal neurons are the largest in the leg area

• M2 map is more diffuse than M1

MAIN SECTION CORTEX

Motor Cortex

precentral gyrusMOTOR

postcentral gyrusSENSORY

III

III

V

VI

contains large pyramidal Betz cells

Gigantocellular pyramidal cells of Betz (layer V)• Cells of origin of the corticospinal fibers• Provide much of the direct projection onto MNs• Present in M1 only

MAIN SECTION CORTEX

Secondary Motor Cortical Areas

• High level planning of movements

• Thinking about movements without actually making them

• Arm the transcortical reflexes – click here for more info

SMA, PMC, PFC

MAIN SECTION CORTEX

Reflexes

• Muscle Spindle• Golgi Tendon Organ• Reciprocal Inhibition• “Crossed Extension” Flexor Reflex• Locomotion• Transcortical Reflex

MAIN SECTION

Muscle Spindle

muscle spindle

quadriceps

biceps tendon

1a or IIafferent

α-MN

γ1- or

γ2-MN

1) Hit tendon

2) Spindle stimulated (1a, II)

3) α-MN fires muscle contracts

γ-MN fires spindle fibers contract

* click on label for details

chain fiber bag fiber

4) Renshaw cell inhibits α-MN

Renshaw cell stimulated

1a*

II*

to spinalcord

γ2-MN*

γ1-MN*

α-MN *

fromspinal

cord

Muscle spindle is involved in…(click here)

MAIN SECTION REFLEXES

CLICK

Golgi Tendon Organ (GTO)

α-MN

α-MN

Ibafferent

Ib afferent

to spinalcord

fromspinal

cord

inhibitory interneuron

1) High muscle tension (force)2) GTO stimulated (Ib)

3) Interneuron inhibits α-MN 4) α-MN decreases firing

5) Decreased muscle tension

Roles of the GTO:• Protect against hurtful muscle stretch• Servo-control force (e.g., combat

weakness due to muscle fatigue)

GTO is involved in:• Clonus• Claspknife reflex

GTO


CLICK

Reciprocal Inhibition

agonist muscle(flexor)

muscle spindle

1a afferent

α-MN to agonist

α-MN to antagonist

antagonist muscle(extensor)

inhibitoryinterneuron

INHIBITED

ACTIVATED


CLICK

“Crossed Extension” Flexor Reflex

• Involves the spinal cord bilaterally• Flexion of one limb evokes extension of the opposite

limb

Applications• Spinal withdrawal reflex

– Hurtful stimulus withdraw stimulated limb + extend opposite limb

• Locomotion– Brainstem activity oscillation of leg flexion and extension


Locomotion Modulationmotor cortex

midbrain locomotorregion (MLR)

corticospinal tracts

reticulospinal tract

Initiate locomotory activity in spinal cord circuits

Modify locomotory activity for voluntary corrections of gait (obstacle avoidance)


Transcortical ReflexesSMA

α-MN

γ-MN

pyramidal tract neuron (PTN)

1) SMA “sets” PTN by low-level firing - Conscious intent (willing the reflex to occur)

2) Muscle is stretched (or skin is touched)

3) Muscle spindle sends 1a afferent to thalamus PTN

4) PTN fires and stimulates MNs in the ventral horn

5) α-MN and γ-MN fire

6) Muscle contracts length is restored

Prefrontal lesion “set signal” is lost motor cortex is hyperactive

Hyperactive palpatory reflex

(“involuntary grasp reflex”)

Hyperactive long loop stretch reflex (“Gegenhalten” – resistance to limb displacement)

These are involuntary

1a afferent


CLICK

Vestibulospinal reflexes can act ALONE if you tilt your head up/down without extending/flexing your neck.Tonic neck reflexes can act ALONE if you extend/flex your neck without tilting your head up/down.

If you combine head tilt with neck flexion/extension, either…- the tonic neck reflex will CANCEL the vestibulospinal reflex, or- the tonic neck reflex will ADD to the vestibulospinal reflex.

Normal Postural Reflexes

Head up Head normal Head downN

eck

exte

nded

Nec

k no

rmal

Nec

k fle

xed

VSR aloneTNR aloneVSR – TNRVSR + TNR

VSR = vestibulospinal reflexTNR = tonic neck reflex

The TNR involves…- the reticulospinal pathway

for somatosensory input.- the tectospinal pathway

for visual input.

To maintain balance, you must have two of the following:

- Somatosensory input- Visual input- Vestibular input

Tips for learning this chart

MAIN SECTION

Abnormal Posture

Vestibulospinal reflexes can act ALONE if you tilt your head up/down without extending/flexing your neck.Tonic neck reflexes can act ALONE if you extend/flex your neck without tilting your head up/down.

If you combine head tilt with neck flexion/extension, either…- the tonic neck reflex will CANCEL the vestibulospinal reflex, or- the tonic neck reflex will ADD to the vestibulospinal reflex.

Normal Postural Reflexes

Head up Head normal Head downN

eck

exte

nded

Nec

k no

rmal

Nec

k fle

xed

VSR aloneTNR aloneVSR – TNRVSR + TNR

VSR = vestibulospinal reflexTNR = tonic neck reflex

The TNR involves…- the reticulospinal pathway

for somatosensory input.- the tectospinal pathway

for visual input.

To maintain balance, you must have two of the following:

- Somatosensory input- Visual input- Vestibular input

1) Know that for VSR alone (head movement only), head up forelimbs flex & hindlimbs extend (and opposite if head is down).

2) Know that for TNR alone (neck movement only), neck extended forelimbs extend & hindlimbs flex (and opposite if neck is flexed).

3) Combining a head movement and neck movement: • If the limb positions resulting from VSR and TNR agree, then the reflexes add (limb hyper-extension/flexion).• If the limb positions resulting from VSR and TNR disagree, then the reflexes cancel (no limb movement).

MAIN SECTION

Abnormal Posture

When the head is passively turned to one side, the looked-at limbs will extend and the others will flex.

This is normal in infants but is a sign of corticospinal lesion in adults.

• Extension of all four limbs, extension of neck, slight intorsion of legs• Used normally when riding a bike• Hyperactive vestibulospinal reflexes – no tonic neck reflex• Caused by a lesion of the upper pons or midbrain (medial descending

motor pathways)– Damage the tectospinal, and corticospinal pathways– Vestibulospinal pathway remains intact

• Usually more serious than internal capsule injury (decorticate posture)

• Flexion of upper limb, extension of lower limb, slight intorsion of legs

• Hyperactive vestibulo-spinal AND tonic neck reflexes (see right)

• Caused by a lesion of the internal capsule (corticospinal pathway)D

EC

OR

TIC

ATE

DE

CE

RE

BR

ATE

MAIN SECTION

CN VII Innervation

to lower facial muscles (left)

to upper facial muscles (left)

R L

CN VII nuclei

Click on a lesion site (circled in purple)NORMAL

MAIN SECTION

CN VII Innervation



R L

CN VII nuclei

X

Lesion of left peripheral CN VII- Left UPPER and LOWER facial weakness- Cannot wrinkle forehead, brow droops, nasolabial fold diminished, mouth droops

MAIN SECTION

CN VII Innervation



R L

CN VII nuclei

X

Lesion of right motor cortex, internal capsule, midbrain, or upper pons- Left LOWER facial weakness only- Upper facial muscles still have innervation from the left corticobulbar tract- Nasolabial fold diminished, mouth droops

MAIN SECTION

Basal Ganglia

Caudate

Putamen

Nucleus accumbens

Globus pallidus, externa (GPe)

Globus pallidus, interna (GPi)

Amydala (part of lymbic system)

Subthalamic nucleus (STN)

Substantia nigra – click here- pars reticulata (SNpr)- pars compacta (SNpc)

Lenticular nucleus = Globus pallidus + Putamen

Striatum = Globus pallidus + Putamen + Caudate

ROSTRAL

CAUDAL

Connections

Diseases

Selection-Brake

NTs

MAIN SECTION

Substantia Nigra - Histology

SNpcdopaminergic

SNprGABAergic

MAIN SECTION BG

Basal Ganglia Neurotransmitters

• Dopamine• GABA• Enkephalin• Substance P• Glutamate• ACh

NOT norepinephrine

MAIN SECTION BG

Basal Ganglia Connections

SNpcGPe

GPi

SNpr

STN

VA/VL

PPPA

SC brainstem/spinal cord

cerebral cortex

caudate / putamenSC = superior colliculusPPPA = peri-pedunculo-pontine areaVA/VL = ventroanterior/ventrolateral nuclei of thalamus

The caudate and putamen receive most of the basal gangia input from the cerebral cortex.

The caudate/putamen send some info to the SNpc, which sends info back.

But most of the caudate/putamen output goes to the GP and SNpr.

The SNpr projects outside the basal ganglia to control head/eye movements.

The GP (GPi, specifically) sends most of the inhibitory input to the thalamus.

GPi also projects to the PPPA, probably for postural control.

The globus pallidus (GPe and GPi) are both in communication with the STN.

= excitatory (Glu)= inhibitory (GABA)= mixed (DA)= unknown

Show selection-brake mechanismMAIN SECTION BG

CLICK

Basal Ganglia Connectionscerebral cortex

SC = superior colliculusPPPA = peri-pedunculo-pontine areaVA/VL = ventroanterior/ventrolateral nuclei of thalamus

= excitatory (Glu)= inhibitory (GABA)= mixed (DA)= unknown

SNpcGPe

GPi

SNpr

STN

VA/VL

PPPA

SC brainstem/spinal cord

caudate / putamen

Person wants to make a voluntary movement

Premotor/motor cortex excite STN

STN excites GPi

GPi inhibits MPGs

DIRECT path from caudate/putamen to GPi INHIBITS GPi

INDIRECT path from caudate/putamen GPe GPi DISINHIBITS GPi

Release the MPGs (those desired for the movement)

Shut down the MPGs (those interfering with the movement)

= excitatory= inhibitory

MAIN SECTION BG

CLICK

Selection-Brake Hypothesis

• Basal ganglia outputs are inhibitory to the thalamus and motor pattern generators (MPGs)

• When a movement is made…– the BG outputs to the desired MPGs decrease their

firing rate (take off the brake).– the BG outputs to interfering MPGs increase their

firing rate (put on the brake).

Click here for the selection brake mechanism

MAIN SECTION BG

Basal Ganglia Diseases

• Damage to BG output cells removes tonic inhibition from all motor pattern generators (MPGs)– Results in sustained contraction in all muscles,

agonist and antagonist– MPGs operate independently and intermittently,

resulting in spontaneous involuntary movements

• Bradykinesia: slow movement

• Akinesia: lack of movement

General Pathophysiology

Parkinson’s Disease Huntington’s Disease

MAIN SECTION BG

Parkinson’s Disease

• Caused by degeneration of the SNpc (dopaminergic)– SNpc modulates putamen and caudate– Putamen/caudate can no longer “focus” the GPi output

• Symptoms– Rigidity, bradykinesia, akinesia, pill-rolling tremor– Can be mimicked by taking dopamine receptor blockers

• Treatment– Give oral L-dopa, a precursor to dopamine

• Too much L-dopa develop chorea/hemiballismus (involuntary, gesture/dance-like movements)

– Ablate or electrically stimulate the STN• This causes chorea in normal subjects, but restores normal function

to Parkinson’s patients

MAIN SECTION BG

Huntington’s Disease

• Caused by damage of the caudate/putamen or STN– Results in excessive activity in the caudate/putamen

• Symptoms– Chorea, athetosis, hemiballismus

• Writhing, purposeful-looking but involuntary movements• Hemiballismus is specifically caused by STN lesion

• Treatment– Drugs that block dopamine receptors in the putamen– Is worsened by L-dopa or dopamine agonists (unlike

in Parkinson’s)

MAIN SECTION BG

Cerebellum

• Folium• Cortical Cells• Deep Nuclei• Connections

MAIN SECTION

Cerebellar Folium

molecular layer

Purkinje cell layer

granule cell layer

white matter

Click here to overlay cell types/connections

MAIN SECTION CB

Cerebellar Folium

Purkinje cell

Granule cell

Climbing fiber

Mossy fiberparallel fiber

terminal(synapse)

dendrite

terminal

dendrite synapse

axon

to the deep nuclei

Click on a cell type:

Stellate cell

Basket cell

Golgi cell

Not shown (can click):

MAIN SECTION CB

Purkinje Cell• One Purkinje cell receives

input from…– One climbing fiber– Many parallel fibers (up to a

million)• Inter-Purkinje cell

connections via parallel fibers allow motor coordination to occur

• Projects to and inhibits the deep nuclear cells

Purkinje cell body

mol

ecul

ar la

yer

gran

ule

cell

laye

r

Purkinje cell dendrite

MAIN SECTION CB

Climbing Fiber• Cell bodies reside in the inferior

olive

• Projects to the Purkinje cell layer, where one climbing fiber synapses with one Purkinje cell– Excitatory– Climbing fiber input weakens the

excitatory effect of parallel fibers on the Purkinje cell

• Fire at high rates when learning movement, low rates during learned movement

mol

ecul

ar la

yer

gran

ule

cell

laye

r

climbing fiber

MAIN SECTION CB

Granule Cell• Receives input from mossy fibers

in the granule cell layer– Extends “claws” to grab the

mossy fiber terminus

• Projects to molecular layer, where the fiber then runs parallel to the folia surface– These “parallel fibers” synapse

on and excite Purkinje cell dendrites

• One synapse per Purkinje cell• One parallel fiber connects many

Purkinje cells– The coincidence of parallel and

climbing fiber excitation of the Purkinje cell results in learning related to coordination

granule cell

parallel fiber

mol

ecul

ar la

yer

gran

ule

cell

laye

r

MAIN SECTION CB

Mossy Fiber• Originates in the…

– Spinocerebellar pathway• Ascending (from spinal cord)• Fibers do not cross• Enters cerebellum through the

inferior cerebellar peduncle– Pons

• Descending (from cerebral cortex)

• These fibers must cross in the cerebral peduncles (corticopontine fibers)

• Enter cerebellum through the middle cerebellar peduncle

• Projects to the granule cell layer, where it synapse on the “claws” of the granule cells– Excitatory

mossy fibers

mol

ecul

ar la

yer

gran

ule

cell

laye

r

MAIN SECTION CB

Inhibitory Interneurons

Stellate cell• Molecular layer

Basket cell• Cell body in molecular layer• Projections wrap around Purkinje cell

Golgi cell• Granule cell layer

basket cell Purkinje cell body

MAIN SECTION CB

Cerebellar Deep Nuclei• Receive inhibitory input from Purkinje cortical cells• Project to brainstem and thalamus – click here• Each nucleus has a separate body map• Help initiate movement – click here

Fastigial (medial) nucleusDentate (lateral) nucleusGlobose/emboliform (intermediate) nuclei

Click on a nucleus:

MAIN SECTION CB

Deep Nuclei and Movement

Deep nuclei probably help initiate movement because…

• their stimulation results in movement.• their damage delays movement initiation.• they send excitatory projections to their targets.

MAIN SECTION CB

Nuclear Functions/Lesions

• Movements involving multiple joints are more impaired than those involving a single joint.

• Patients may try to compensate by moving more slowly or moving one joint at a time.

• Lesions prevent several types of motor learning.

Nucleus Input Function Lesion results in…

Fastigial (medial) Vestibular Control upright stance against gravity

Falls to the side of the lesion

Globose/ emboliform (interposed)

Cerebral cortex Spinal cord

Balance agonist and antagonist muscles at a single joint

Ipsilateral action tremor during voluntary movements (e.g. reaching)

Dentate (lateral) Cerebral Cortex (1) Combined digit movements

(2) Arm/leg reaching to a visual target

(1) Incoordination of digits(2) Overshoot targets in

reaching with arm/leg

MAIN SECTION CB

Cerebellar Connections

ventrolateral thalamus

red nucleus

vestibular nuclei

reticular formation

All cerebellar projections are excitatory

MAIN SECTION CB

Autonomic Nervous System

• Efferents/Afferents• Circumventricular Organs• Functions

– Baroreceptor– Respiration– Micturition

• Periaqueductal Gray (PAG)

MAIN

Viscero-Motor Efferents / Visceral AfferentsSympathetic Efferents• Output arises from the intermediolateral (IML) cell column from T1 to L2• Relay through sympathetic trunk

Parasympathetic Efferents• Sacral output

– From cells similar to the IML in the sacral cord– Relays through ganglion cells in the pelvic plexus

• Cranial output– Runs in CN III, CN VII, CN IX, CN X– Arises in nuclei associated with the CNs

Visceral Afferents• Return to the CNS with sympathetic & parasympathetic efferent fibers• Cell bodies are in dorsal root or CN ganglia• Sympathetic afferents: Pain (synapse on cells of spinothalamic tract)• Parasympathetic afferents: State of the viscera

– CN VII, CN IX, CN XMAIN SECTION

CN III Parasympathetics

Edinger-Westphal nucleus

CN III nucleus

CN IIIciliary ganglion

to pupilloconstrictor and ciliary muscles

Pupillary Constriction and Accommodation

MAIN SECTION

CN VII and IX Parasympathetics

Viscero-motor• Parasympathetic fibers in CN VII and IX arise from

“salvatory/lacrimal nuclei”– Scattered cells in the pons and upper medulla– Relay through submandibular, pterygopalatine, otic ganglia

• Responsible for secretion from salvatory glands, lacrimal gland, and other glands in mouth and nasal cavity

Visceral afferents• Synapse in the nucleus of the solitary tract• CN VII: Taste info• CN IX: Info from carotid body/sinus, pharynx

MAIN SECTION

CN X Parasympatheticsdorsal nucleus of CN X nucleus of the solitary tract

nucleus ambiguus

= secretomotor efferents= vasomotor efferents= visceral afferents

GUT

HEART

PHARYNX/ LARYNX

MAIN SECTION

Circumventricular Organs

area postrema

dorsal nucleus of CN X


solitary tract

CN XII nucleus

• Area postrema, subfornical organ, organum vasculosum of the lamina terminalis (OVLT)

– Small areas around the 3rd and 4th ventricles• LACK a blood brain barrier

– Chemosensitive neurons detect circulating molecules/ hormones (AII, insulin, vasopressin)

MAIN SECTION

Baroreceptor Reflex


nucleus ambiguus

caudal ventrolateral medulla

rostral ventrolateral medulla

intermedio-lateral column

peripheral arterioles

aortic arch baroreceptors

carotid sinus baroreceptors

tonic

= inhibitory= excitatory= parasympathetic= sympathetic

MAIN SECTION

RespirationForebrain

Parabrachial nucleus

Lung stretch receptorsCarotid body chemoreceptors Intrinsic chemoreceptors

Nucleus of the solitary tract

Rostral inspiratoryExcitatory

Caudal expiratoryExcitatory

Botzinger complexReciprocal inhibition

Phrenic motorneuronsExt. intercostals

Int. intercostal motorneuronsAbdominal muscles

Ventral respiratory pre-motor cells

= excitatory= inhibitory

Pre-Botzinger cellsRespiratory rhythm

VENTROLATERALMEDULLA

MAIN SECTION

MicturitionHypothalamus, PAG

pontine micturition center (parabrahial region)

sacral spinal cord

bladder

= afferent= efferent

Short loop reflex

Long loop reflex

MAIN SECTION



sacral spinal cord

bladder


Short loop reflex- Bladder stretch triggers bladder contraction- Used by infants

MAIN SECTION



sacral spinal cord

bladder


Long loop reflex- Hypothalamic/PAG input plus bladder stretch info control bladder contraction- Used by adults for better control of micturition- GABAergic neurons play a role

MAIN SECTION

Periaqueductal Gray (PAG)• Integrates several autonomic reflexes

• Receives visceral afferent projections (like the parabrachial nuclei)

• Outputs: hypothalamus, amygdala, other forebrain areas

PAG region stimulated Evokes… In response to…Lateral Fight or flight Superficial (escapable) pain

Ventrolateral Quiescence Deep (inescapable) pain

PAG

MAIN SECTION

Eye Movements / Ocular Dominance

Goal Eye movement Function

Stabilize the eye when the head moves (reflexive)

Vestibulo-ocular Use vestibular input to hold images stable on retina during brief/fast head movement

Optokinetic Use visual input to hold images stable on retina during sustained/slow head movement

Keep the fovea on a visual target (volitional control)

Saccade Bring new objects of interest into the fovea

Smooth pursuit Hold image of a moving target on the fovea

Vergence Adjust the eyes for viewing distances in depth (converge for near, diverge for far)

Ocular Dominance Columns

MAIN

Vestibulo-Ocular Reflex (VOR)

Secondary pathway (visual cortex cerebellar flocculus)

semicircular canal

vestibular nuclear complex

motor nuclei to eye muscles

eye muscles

If the head moves left quickly, VOR causes the eyes to move right.

But the VOR can get “out of tune” if it operates alone. Therefore, a secondary pathway (long latency, multisynaptic, involving the visual system and cerebellum) synapses on ocular motorneurons and adjusts the gain of the reflex.

The VOR depends on the stimulation of kinocilium in the vestibular labyrinth.

MAIN SECTION

CLICK

Optokinetic Reflex

• Senses motion of the visual background (involves the extrastriate cortex)

• Nystagmus– Slow phase: Compensatory tracking movements

(smooth pursuit)– Fast phase: Anticipatory fast movement to reposition

eyes after they reach the edge of the orbit (saccade)

Eye

pos

ition

(deg

rees

)

Time (sec)

MAIN SECTION

Ocular Dominance Columns (ODCs)• Features of ODCs

– Located in V1– Develop prenatally– Visual input to each ODC is monocular (by looking out of one

eye, you drive just one set of ODCs)

• Development of binocular vision– Requires visual experience and development of inter-ODC

connections– Occurs during the critical period (60-90 days postnatally)

• Conditions that result in binocular vision impairment– Strabismus: Misaligned eyes

• If subject becomes accustomed to using just one eye at a time, left and right ODCs will never be co-stimulated and no inter-ODC connections will develop

– Anisometropia: One eye more nearsighted than the other, due to unilateral amblyopia (poor visual acuity)

• There is more metabolic activity in the non-amblyopic columns

MAIN SECTION

Periventricular nucleus

Lateral hypothalamic area

Dorsomedial nucleus

Supraoptic nucleus

Ventromedial nucleus

Arcuate nucleus

fornix

median eminence

PVZ

MHA

LHA

ZONE STRUCTURE(S)

Paraventricular nucleus (not shown)

OTHER

PVZ = Periventricular zoneMHA = Medial hypothalamic zoneLHA = Lateral hypothalamic zone

Hypothalamus

Suprachiasmatic nucleus (not shown)

Hypothalamic Inputs

Hypothalamic OutputsAnterior Pituitary

Click on a zone, nucleus, or button

Posterior PituitaryPhysiological Regulation

MAIN

Hypothalamic Nuclei

fornix

median eminence

lateral hypothalamic area

ventromedial nucleus

fornix

arcuate nucleus

median eminence

paraventricular nucleus

orexin cells?

MAIN SECTION

Hypothalamic Nuclei

fornix

median eminence

supraoptic nucleus

anterior hypotha-lamic area

anterior commissure

suprachiasmatic nucleus

MAIN SECTION

Hypothalamic Nuclei

fornix

median eminence

lateral hypothalamic area ventromedial

nucleus

arcuate nucleus (dopa-minergic cells)

paraventricular nucleus

optic tract

dorsomedial nucleus

MAIN SECTION

Inputs to Hypothalamus

Type Structure Carries info about…Extrinsic Reticular formation Temperature

Retina Light/dark cycle (to suprachiasmatic nucleus)

Nucleus of the solitary tractParabrachial nucleus

Taste, visceral sensation

Olfactory cortex Food, sexual attractants

Amygdala, hippocampus, prefrontal cortex (limbic input)

Cognition

Circumventricular organs Osmolality of bloodPeptide hormones in blood (AII, atrial natiuretic factor)

Intrinsic Thermoreceptors Local blood temperature

Osmoreceptors Local CSF ionic strength

Chemoreceptors Hormones (e.g., leptin, ghrelin)

MAIN SECTION

Outputs from Hypothalamus

From… To… EffectLateral hypothalamusParaventricular nucleus

Autonomic nuclei in spinal cord, brainstem(PAG, parabrachial nuclei, nucleus of the solitary tract, dorsal vagal nucleus, ventrolateral medulla, IML)

Control body temp (sweating, shivering, vasoconstriction)

Releasing hormone neurons in periventricular zone (arcuate nucleus and part of the paraventricular nucleus)

Median eminence Control of anterior pituitary

Supraoptic and paraventricular nuclei

Posterior pituitary Secrete ADH, oxytocin

Scattered large neurons Cerebral cortexLimbic structures

Not clear; presumably contribute to hypothalamic control of behavior

MAIN SECTION

Anterior Pituitary

CRHTRHGnRHGHRHSomatostatinDopamine

ACTHTSHLH/FSHGHGH/TSHMSH

median eminence

periventricular zone of the hypothalamus(arcuate nucleus and part of the paraven-tricular nucleus)

hypothalamic releasing hormones

corresponding anterior pituitary hormones

Hypothalamic cell axons terminate in the median eminence and secrete hormones into the fenestrated pituitary portal capillaries

MAIN SECTION

Posterior Pituitary

supraoptic nucleus / paraventricular nucleus

Posterior pituitary hormones:- oxytocin- ADH (vasopressin)

median eminence

Hypothalamic cell axons terminate in the posterior pituitary and secrete hormones into the fenestrated pituitary capillaries

MAIN SECTION

The hypothalamus regulates…

• Body temperature• Body weight• Ionic balance• Blood pressure (chronic)• Circadian rhythm• Reproduction• Response to stress

MAIN SECTION

Body Temperature

spinal cord

reticular formation

intrinsic thermoreceptors

releasing hormone neurons

anterior hypothalamus

TSH, GH, somatostatin

lateral hypothalamus

autonomic nuclei

sweating, shivering, etc.

cerebral cortex

behavior?

inputs

outputs/effects

MAIN SECTION REG

Body Weightviscera (gut)

food intake, gut distension

NTS / parabrachial nuclei

tonguetaste

NTS

olfactory cortexsmell

fat cells leptin(receptors in dorsomedial nucleus)

gut ghrelin

orexin

suppress food intake / increase metabolism

promote food intake / decrease metabolism

promote food intake / stabilize sleep

autonomic nuclei

pituitary

inputs

outputs/effects

MAIN SECTION REG

Ionic Balance

circumventricular organs

blood osmolality, peptide hormones

intrinsic osmorecptors

CSF tonicity

vena cava / R atriumblood volume

NTS

posterior pituitary

ADH

alter urine tonicity, Na+ and H2O intake

inputs

outputs/effects

MAIN SECTION REG

Blood Pressure (Chronic)

baroreceptors

NTS

angiotensin II

circumventricular organs

autonomic nuclei

vasoconstriction

inputs

outputs/effects

posterior pituitary

ADH

vasoconstriction, anti-diuretic action

on kidney

MAIN SECTION REG

Circadian Rhythm

retina

inputs

outputs/effects

couple the circadian rhythm to the

light/dark cycle

The suprachiasmatic nucleus of the hypothalamus (and the surrounding region) sets the circadian rhythm.Input from the retina allows the cycle to be coupled to the light/dark cycle.

suprachiasmatic nucleus

MAIN SECTION REG

Reproduction

olfactory system

gonadal steroids

inputs

outputs/effects

reproduction

amygdala / hippocampus

emotion, memory

MAIN SECTION REG

Response to Stress

ascending catecholamine

systems

limbic system

inputs

outputs/effects

CRH

ACTH

glucosteroid release from adrenal cortex

change glucose metabolism and

energy use

Glucosteroids can inhibit the hypothalamus to terminate the stress response.Chronic glucocorticoids can cause neuronal and other damage, possibly contributing to post-traumatic stress disorder, depression, and other disorders.

MAIN SECTION REG

Limbic Systemcingulate gyrus / cingulum

amygdala

fornix

hippocampus

parahippocampal gyrus

dentate gyrus

mammillary body

stria terminalisolfactory bulb

anterior commissure

hypothalamus

orbital/medial prefrontal cortex

Not shown: olfactory cortex

MAIN

Amygdala

central nucleus

basal nucleus

accessory basal nucleus

lateral nucleus

medial nucleus

PAC

PAC = periamygdaloid complex

Dorsal nuclei

Deep nuclei

nucleus basalis of Meynert

amydala

entorhinal cortex

Role

Inputs/Outputs

MAIN SECTION

The amygdala is involved in…

• Making cortical cells more responsive to other synaptic inputs– Most cells of the amygdaloid nuclei are cholinergic– Help activate (desynchronize) cortex during waking state

• Fear conditioning– Modulate brainstem reflexes in response to emotional status

• Recognizing fear in others

• Depression (may show increased activity)

• Kluver-Bucy Syndrome– Associated with temporal lobe ablation– Cannot recognize the significance of objects; loss of fear; failure

to learn

MAIN SECTION AMYG

Inputs/Outputs

ascending sensory system

vision, olfactory, auditory, somatosensory

inputs

outputs/effects

autonomic cell groupslateral hypothalamus, PAG,

parabrachial nucleus, NTS, dorsal nucleus of CN X, ventrolateral medulla

influence HR, BP, gut/bowel/respiratory/bladder function, etc.

orbital/medial prefrontal cortex

determine whether sensory stimulus is

rewarding or aversive; set mood

direct OR via mediodorsal thalamus

thalamic relay nucleus

primary sensory cortex

secondary association

cortex

posterior intralaminar

thalamic nuclei

MAJOR SHORTCUT

The shortcut afferent pathway produces your initial “gut reaction” to a potentially threatening situation, before the major pathway kicks in.

feedback

OR via the ventromedial striatum

Amygdala

MAIN SECTION AMYG

Olfactory Bulbolfactory nerves

glomerular formations

mitral cells

granule cells

Mitral cells• Principal relay cells• Dendrites extend to the glomerular formations and synapse with olfactory receptor

neurons (reciprocal, dendritodentritic synapses)

Granule cells• Deep

– Processes interact with mitral cell dendrites in the external plexiform layer– GABAergic

• Superficial– Synapse with mitral cell dendrites– GABA (most), dopamine, neuropeptides (enkephalin, substance P, neurotensin)

MAIN SECTION

Olfactory Cortex

primary olfactory cortex

olfactory tract

putamen

nucleus accumbens /olfactory tubercle

lateral striate arteries

• At the junction of frontal and temporal cortices

• Axons of mitral cells run in olfactory tract to primary olfactory cortex

• Olfactory cortex is the major center for odor detection and discrimination

• Efferent info is integrated with other sensory modalities in the orbital part of the frontal cortex

• Other outputs: amygdala, hippocampus, hypothalamus, mediodorsal thalamic nucleus

MAIN SECTION

Olfactory Cortex

primary olfactory cortex

olfactory tract

putamen

nucleus accumbens /olfactory tubercle

lateral striate arteries

• At the junction of frontal and temporal cortices

• Axons of mitral cells run in olfactory tract to primary olfactory cortex

• Olfactory cortex is the major center for odor detection and discrimination

• Efferent info is integrated with other sensory modalities in the orbital part of the frontal cortex

• Other outputs: amygdala, hippocampus, hypothalamus, mediodorsal thalamic nucleus

Nucleus accumbens- “Reward” center- Contains mostly GABAergic neurons- Receives input from the amygdala and hippocampus

MAIN SECTION

Hippocampus

tail of caudate

dentate gyrus

CA1

CA3

subiculum

pre-subiculum

para-subiculum

entorhinal cortex

inferior temporal area

Role

Inputs/Outputs

Alzheimer’s Disease

Information Flow

MAIN SECTION

The hippocampus is involved in…• Memory processing (especially for spatial orientation)

– Hippocampal “place cells” fire when animal is in a particular spatial location, related to surrounding sensory stimuli

• Formation of new memories– Hippocampal lesion inability to form new memories (old memories

remain intact)

• Memory deficits following ischemia or seizures– CA1 is the most commonly damaged brain area after ischemia or

epileptic seizures• Ischemia cells are depolarized NMDA receptors allow Ca2+ and Na+ to

enter cell more depolarization excitotoxicity

• Kluver-Bucy Syndrome– Associated with temporal lobe ablation– Cannot recognize the significance of objects; loss of fear; failure to learn

• Alzheimer’s Disease

MAIN SECTION HIPP

Inputs/Outputs

info from multisensory

association cortical areas

visual, auditory areas of inferior and superior temporal cortex

perirhinal/entorhinal cortex

inputs

outputs/effects

hypothalamus

Hippocampus

feedback prefrontal / cingulate cortical areas

basal ganglia (ventral)

direct O

R via ant. t

halamic nuc. /

mammillary

nuclei

MAIN SECTION HIPP

Hippocampus

tail of caudate

dentate gyrus

CA1

CA3

subiculum

pre-subiculum

para-subiculum

entorhinal cortex

inferior temporal area

to frontal cortex, anterior thalamus, hypothalamus

to the neocortex

sensory inputs from cerebral cortex

Role

Inputs/Outputs


Hide Information Flow

MAIN SECTION HIPP

CLICK


CA1

Sub

PreSubParaSub

EC

CA3

DG

β-amyloid plaques

tangles (intracellular)

CA1

• Entorhinal cortex and CA1 are severely damaged during early Alzheimer’s– High amounts of tangles in these areas

• Tangles develop before plaques, but plaques mark beginning of the disease– Plaques are prevalent in the cerebral cortex outside the hippocampal formation

MAIN SECTION HIPP

Orbital/Medial Prefrontal Cortex (OMPC)Orbital prefrontal cortex Medial prefrontal cortex

inputs

outputs/effects

multimodal sensory inputs

assessment of food

amygdala / hippocampus

hypothalamus, PAG

control visceral functions

appropriate choices

reward/aversion

control of mood

MAIN SECTION

Sleep

• Electroencephalogram (EEG)• Stages• Ascending Reticular Activating System

MAIN

Electroencephalogram (EEG)

Synchronized waves

• High amplitude, low frequency

• Represent wave summation

• Result when similar events coincide

• Ex: δ waves of sleep

Desynchronized waves

• Low amplitude, high frequency

• Represent wave subtraction

• Result when disparate events coincide

• Ex: wakefulness, REM

MAIN SECTION

Stages of Sleep

• Stage 1: Alpha waves (still relatively desynchronized)

• Stage 2: Sleep spindles

• Stage 3-4: Delta waves (synchronized) – deep sleep, slow waves

• REM (Rapid Eye Movement):– Very desynchronized but person is still asleep (“paradoxical”)– No movement except for the extraocular and middle ear muscles, and penile erection– Loss of thermoregulation– Dreaming, sleep apnea occur; dreaming often reflects experiences over the past few days– Initiated in the rostral pons, LGN, and occipital cortex– Depends on cholinergic inputs from the upper pons to thalamus

These stages cycle several times throughout the night.

MAIN SECTION

Ascending Reticular Activating System

thalamus

Nucleus basalis of Meynert (ACh) [not shown]- Implicated in sleep and wakefulness- Projects to all parts of forebrain except basal ganglia- Histology

Laterodorsal tegmental nucleus (LDT) (ACh)

Pedunculopontine tegmental nucleus (PPT) (ACh)

Locus coeruleus (norepinephrine)- Contributes to changes in thalamocortical activity- Histology

Raphe nucleus (5-HT)- Caudal spinal cord- Rostral all parts of forebrain- Atlas

Thalamic relay nuclei (e.g., LGN)

Reticular nucleus (GABA)- Receives synapses from thalamocortical, cortico-thalamis axons (connect cortex and principal thalamic nuclei)- Project back onto the principal thalamic nuclei- Histology

This system is active during wakefulness (and its stimulation causes waking). It is inactive during sleep (and its transection causes coma).

Neurotransmitters Sleep Initiation

MAIN SECTION

Ascending Reticular Activating SystemNucleus basalis of Meynert (Ach) [not shown]- Implicated in sleep and wakefulness- Projects to all parts of forebrain except basal ganglia- Histology

Laterodorsal tegmental nucleus (LDT) (Ach)

Pedunculopontine tegmental nucleus (PPT) (ACh)

Locus coeruleus (norepinephrine)- Contributes to changes in thalamocortical activity- Histology

Raphe nucleus (5-HT)- Caudal spinal cord- Rostral all parts of forebrain- Histology

Thalamic relay nuclei (e.g., LGN)

Reticular nucleus (GABA)- Receives synapses from thalamocortical, cortico-thalamis axons (connect cortex and principal thalamic nuclei)- Project back onto the principal thalamic nuclei

This system is active during wakefulness (and its stimulation causes waking). It is inactive during sleep (and its transection causes coma).

reticular nucleus

ventrolateral thalamic nucleus

RAT BRAIN – Stained for GABA

MAIN SECTION SYS

Neurotransmitter Systems

Wakefulness Slow wave sleep REM sleep

Norepinephrine(locus coeruleus)

ACTIVE INACTIVE INACTIVE

Serotonin(raphe nuclei)

ACTIVE INACTIVE INACTIVE

ACh(LDT/PPT)

ACTIVE INACTIVE ACTIVE*

Both norepinephrine and ACh facilitate the responsiveness of post-synaptic neurons.

* The ACh input here is responsible for the paradoxical situation in REM sleep.

Ascending Reticular Activating System

MAIN SECTION SYS

Sleep Initiation

depolarizeAChNE

5-HT

depo

larize

hyperpolarize

sensory afferentseye, spinal cord, etc.

CORTEX

RETICULARNUCLEUS

THALAMICRELAY

NUCLEUS(TRN)

Add ascending ACh, NE, 5-HT input

RN inhibition of TRN is blocked

TRN cells respond to sensory input with a tonic firing pattern ( wakefulness)

Remove ascending ACh, NE, 5-HT input

RN inhibition of TRN is released RN bursting

TRN cells cannot respond to sensory input and fire in a rhythmic bursting pattern ( sleep spindles in early sleep stages)

thalamocortical neuron

= Excitatory (glutamate)= Inhibitory (GABA)

WAKEFULNESSSLEEP INITIATION

MAIN SECTION SYS

CLICK

Memory

Types of amnesia• Anterograde

– Inability to form new memories post-trauma– May be able to form short-term working memories (minutes), but

cannot hold them• Retrograde

– Loss of memories from a few seconds to a couple years pre-trauma– May have more distant memories

Types of memory• Implicit (e.g., procedural)• Explicit (a.k.a declarative)• Working

MAIN

Memory Disorders• Alzheimer’s Disease• Lewy Body Dementia• Korsakov’s syndrome

Implicit Memory

• Subconscious– Skills/procedures/habits– Simple classical conditioning

• Learned by repetition

• Examples: riding a bike, playing an instrument

• Brain regions involved:– Striatum, cortex, cerebellum– Not the hippocampus

Procedural

MAIN SECTION

Explicit Memory

• Conscious– Episodic: places and events– Semantic: names and facts

• Brain regions involved– Medial temporal lobe (hippocampus and associated areas)– Entorhinal and perirhinal cortices project to the hippocampus and are

especially important in memory

• Memory storage: Sensory association cortical areas– Lateral temporal, parietal, posterior insular cortex– Memory consolidation depends on the interaction between these areas

and the limbic structures

• Is affected in Korsakov’s Syndrome and most cases of amnesia

Declarative

MAIN SECTION

Working Memory

• Short term (i.e., seconds to minutes)

• Example: holding a conversation

• Brain regions involved– Prefrontal cortex, areas of the parietal and temporal

lobes (relatively unknown)• Lesion to dorsolateral prefrontal cortex disrupts performance

on short delay tasks– Not the hippocampus

MAIN SECTION

Korsakov’s Syndrome• Lack of vitamin B1 damage along 3rd ventricle

– Seen in alcoholics due to vitamin deficiency

• Presentation– Anterograde amnesia– Patients do not have a good awareness of their amnesia (unlike patients

with medial temporal lobe lesion)

• Involves the mammillary bodies, dorsal thalamus, anterior thalamus

3rd ventricle

mammillary bodies

NORMAL KORSAKOV’S

no mammillary bodies

MAIN SECTION

Lewy Body Dementia• Closely related to Parkinson’s Disease

• Intracellular inclusions of protein α-synuclein neuronal dysfunction

• Dementia is similar to that found in Alzheimer’s

MAIN SECTION

Lewy bodies

Language ProcessingCODES:• Visual / orthographic• Auditory / phonological• Syntactic / grammatical• Semantic / meaning• Articulatory / speech motor planning

Evidence against the Wernicke-Gershwind model:Existence of phonological and surface dyslexia

Dual route model:Damage to lexical, whole-word route leads to problems reading irregular words like “have”

Aphasia

MAIN

Note: This is not a thorough treatment of language processing, but these are the only questions I’ve seen on past exams…

AphasiaLoss or impairment of language function (caused by brain damage) during speech, hearing, reading, or writing

Broca’s Wernicke’sClick on an aphasia

MAIN SECTION

Broca’s Aphasia• Aphasia with difficulty in language expression• Caused by lesion to the left frontal lobe

– Note the proximity of Broca’s area to the motor cortex, specifically the region controlling the mouth and lips

control of mouth/lips

MAIN SECTION

Wernicke’s Aphasia

• “Receptive aphasia” with language comprehension difficulty • Caused by lesion to the left posterior temporal lobe

– Note the proximity of Wernicke’s area to the auditory cortex

MAIN SECTION

References

Bear, M.F., Connors, B.W., and Paradiso, M.A. Neuroscience: Exploring the Brain (2nd ed.). Baltimore: Lippincott Williams & Wilkins, 2001.

“Digital Anatomist: Interactive Brain Atlas.” http://www9.biostr.washington.edu/da.html.

Molavi, D.W. “Neuroscience Tutorial.” http://thalamus.wustl.edu/course/.

Monroe, Eric. “Brainstem Lesions,” 2006.

Neuroscience 2006 Course Notes, Part II. Washington University School of Medicine, St. Louis.

Woolsey, T., Hanaway, J., and Gado, M.H. The Brain Atlas (2nd ed.). New Jersey: John Wiley & Sons, Inc., 2003.

MAIN

http://www9.biostr.washington.edu/da.html

http://thalamus.wustl.edu/course/



Documents

Cindy Montana's Neuro Exam 2 Review