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THE NERVOUS
SYSTEM
Divisions of the nervous system
Protection of the Brain: The Cranial Meninges
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Cranium is covered with protective membranes =
meninges
– Cranial meninges are continuous with spinal
meninges
– 3 layers: 1. outer, fibrous dura mater – forms sheets
(falx) that separate the cerebrum and the cerebellum
into the hemispheres and the cerebellum from the
cerebrum
– comprised of an outer endosteal layer and and inner
meningeal layer
2. middle arachnoid mater – avascular layer
-named for the spider-like struts (trabeculae) that
connect the arachnoid to the underlying pia mater
3. inner, thin pia mater – vascular connective tissue
-makes direct contact with brain tissue
-cells of the pia mater are impermeable to the passage
of many substances
-this membrane is pierced by tiny capillaries that
nourish the brain tissue – arise from the larger
capillaries that travel within the dura mater
•large spaces for the circulation
of blood can be found between the
two dural layers = sinuses
e.g. superior sagittal sinus
• also large veins run through the
subarachnoid space
e.g. cerebral veins
-there are spaces between these
membranes
A. subarachnoid space:
between the arachnoid and pia
maters
-for the circulation of CSF
B. subdural space:
between the arachnoid and the
dura mater
C. epidural space – between
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Medical Application
Pathology
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There are three types of hemorrhage involving the meninges
Epidural bleeding is rapid because it is usually from arteries, which are high pressure.
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A subarachnoid hemorrhage is acute bleeding under the arachnoid; it may occur
spontaneously or as a result of trauma.
A subdural hematoma is located in a separation of the arachnoid from the dura mater.
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Epidural bleeds from dural arteries can grow until they reach their peak size at six to eight hours post
injury, spilling from 25 to 75 ml of blood into the epidural space
the bleeding strips the dura from the inside of the skull, causing an intense headache.
the bleeding is usually restricted to defined locations as its expansion stops at skull's sutures, where the
dura mater is tightly attached to the skull.
Bleeding into the epidural space in the spine may also cause epidural hematoma. These may arise
spontaneously (e.g. during childbirth, or as a rare complication of anaesthesia (such as epidural
anaesthesia)
bleeding is likely to be venous.
may present as pain, muscle weakness, or bladder and bowel dysfunction.
estimates vary from 1 per 10,000 to 1 per 100,000 epidural anaesthetics
subdural bleeding usually results from tears in veins that cross the subdural space.
This bleeding often separates the dura and the arachnoid layers.
Subdural hemorrhages may cause an increase in intracranial pressure (ICP), which can cause
compression of and damage to delicate brain tissue.
the blood may be aspirated surgically to remove the mass and reduce the pressure it
puts on the brain
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The hematoma is neurosurgically evacuated through a burr or craniotomy.
The diagnosis of epidural hematoma requires a patient to be cared for in a facility with a
neurosurgeon on call to decompress the hematoma if necessary and stop the bleed by ligating
the injured vessel branches.
subarachnoid
hemorrhage
Protection of the Brain: CSF
– CSF: 80 to 150 mL of clear, colorless liquid
• replaced completely up to three times per day
• glucose, proteins, lactic acid, urea, ions
• made by specialized cells in the lateral ventricles – choroid plexus
– networks of capillaries in the walls of the ventricles
– covered by ependymal cells (epithelial) cells) that filter the blood plasma and produce CSF by
secreting it
– these cells are capable of allowing passage of certain substances from the blood through them
into the CSF – inhibit the passage of others
• continually circulates – ventricles of the brain and central canal to subarachnoid space
• functions:
– 1. Chemical protection: provides an optimal chemical environment for neuronal signaling
– 2. Mechanical protection: acts as a shock absorber, preventing direct physical contact between
brain tissue and the bones of the cranium or vertebral canal
– 3. Circulation: allows the exchange of nutrients and waste products between the blood and
nervous tissue
Flow of CSF
-CSF forms in the choroid plexi of the lateral ventricles and flows into the 3 rd ventricle through the interventricular
foramina
-the 3rd ventricle adds to the CSF volume
-the CSF then flows into the 4th ventricle via and cerebral aqueduct (passes through the midbrain) – contributes more
volume
-then enters the subarachnoid space via openings in the 4 th ventricle called apertures
-also enters the central canal of the SC
-circulation is driven by ciliary action and pressures provided by the blood and gravity – 10 mm Hg
Circulation of the CSF
•CSF is gradually reabsorbed into the
blood through fingerlike projections
into the dural venous sinuses = arachnoid
granulations
-absorbed at about 20ml/hr which equals
its rate of formation
•interfering with the drainage of CSF
into the subarachnoid space can result
in accumulation of CSF in the ventricles
& CSF pressure rises = hydrocephalus
(implantation of a shunt – lateral ventricle
into the superior vena cava or abdomen)
Blood-Brain Barrier (BBB)
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within the body the capillaries are sites of exchange between materials in the blood and
the ECF – filtration of the blood plasma by capillary cells helps form the ECF
most locations within the body, this exchange is very free
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the capillary walls are formed of a single layer of cells = endothelium
the cells are joined loosely and are connected by numerous gap junctions and pores between
the cells
this allows for an easy diffusion of many plasma components (except large plasma proteins)
between the cells themselves
so even small changes in blood plasma contents can dramatically effect the ECF composition
however, in the brain, the capillary cells are careful as to what is filtered out of the blood
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the cells of the endothelium are very tightly linked together
the cells are joined by tight junctions to restrict the flow of materials among them and through
them into the ECF surrounding the brain
so materials must directly passage the cells themselves to contribute to the ECF
so the passage of things like glucose, amino acids, ions are carried through the cells by carrier
proteins
But lipid-soluble materials and gases (oxygen) can cross easily through the PM of the
endothelial cells
so transport between the cells is Anatomically Prevented and transport through the cell is
Physiologically Restricted = BBB
role of astrocytes in the BBB: 1. signal the capillaries to “get tight”
• 2. participate in the transport of some ions like K+
The blood supply to the brain
• Arterial blood reaches brain via internal carotid, vertebral arteries
• Venous blood leaves via internal jugular veins
-transient ischemic attacks (TIA): no permanent neurologic damage
-temporary cerebral dysfunction caused by impaired blood
flow to the brain
-dizziness, weakness, blurred vision, slurred speech,
paralysis
-persists from 5 to 50 minutes
-caused by emboli (blood clots), atherosclerosis
-cerebral vascular accident (CVA): stroke
-affects 500,000 people per year
-third leading cause of death
-permanent cerebral dysfunction caused by impaired blood
flow to the brain
-sudden onset of symptoms
-caused by cerebral hemorrhage (anuerysm), blood clot, atherosclerosis
-treatment – rapid administration of clot-dissolving drugs (e.g. tPA) if stroke
is caused by a clot
Neuronal Organization
Neural Organization: Pathways
•A neural pathway is comprised of centers/cell bodies and
tracts
• Sensory pathway
– Ascending
– Information from sensory receptors to CNS
• Motor pathway
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Descending
Information from CNS to skeletal muscle or glands
Direct pathways – cause precise, voluntary movements
Indirect pathways – result in involuntary movement (from brain
stem)
Major Regions of the Brain
Figure 15.1 Major Divisions of
the Brain
Major Regions of the Brain
Major Regions and Landmarks
• Cerebrum = largest portion
-left and right cerebral hemispheres divided by the longitudinal fissure
-connected by the corpus callosum
-folded into ridges and grooves: grooves = sulci
-sulci divide the cerebrum into lobes
-ridges = gyri (gyrus)
–Central sulcus
•Frontal and parietal
lobes
Major Regions and Landmarks
-outer layer of the cerebrum =
cerebral cortex
-area for specific processing of
sensation, -area of voluntary
movement, speech, all thought
processes
-motor and sensory areas
e.g. primary visual, auditory &
gustatory areas
e.g. primary motor area
(precentral gyrus): controls
voluntary contractions
-plus association areas for
integration and analysis of
incoming info & help in
making of “decisions”
The Cerebrum
-cerebrum is comprised of:
1. white matter - neurons with
long, myelinated axons
-organized into tracts
A. Association tracts: conduct
impulses between gyri within
a hemisphere
B. Commisural tracts: connects
gyri in one hemisphere to
others in the other hemisphere
1. corpus callosum
2. anterior commisure
3. posterior commisure
C. Projection tracts: tracts that connect
cerebrum to the lower parts of the
CNS (e.g. Thalamus, brainstem)
2. gray matter – outer edge of the
cerebrum = cerebral cortex (2-4 mm
thick = billions of neurons)
-localized areas of gray matter
called the basal ganglia
Basal Ganglia
-nuclei found deep within the cerebrum
- links to the midbrain
- receives input from the cortex & provides output to the motor areas of the cortex via the thalamus
-integrates motor commands
-regulates the initiation & termination of muscle mve.
-also functions to anticipate body movements & controls subconscious contraction of skeletal muscle
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comprised of the:
1. striatum
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caudate nucleus: activity occurs prior to eye movements
putamen: precedes or anticipates body movements
nucleus accumbens
2. globus pallidus: regulates muscle tone for movements
3. claustrum
4. substantia nigra: high concentration of dopanergic neurons
5. subthalmic nucleus
Medical application: Basal Ganglia
-damage to the basal ganglia:
-results in uncontrollable, abnormal body movements
-muscle rigidity may develop and tremors
-Parkinson – neurons that extend from the substantia nigra
to the caudate nucleus and putamen
degenerate
-loss of dopamine releasing neurons – increase in
muscle tone and stiffness
-Huntington - hereditary disorder
-caudate nucleus and putamen degenerate with loss
of neurons that release GABA or ACh
-spasmatic muscle contractions and loss of mental
status
Integrative Functions and the Reticular Activating
System
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integrative function of the cerebrum
– processing of sensory information (analysis and storage) and making a decision
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includes sleep and wakefulness, learning and memory, emotional responses
wakefulness/sleep: role of the RAS
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24 hr cycle called circadian rhythm
established by the hypothalamus and epithalamus
transition between the states of sleep and wakefulness is controlled by the RAS
portion of the cerebral cortex that is activated upon sleep arousal
when active – transmission of signals to many areas of the cortex both directly and via the
thalamus = general increase in cortical activity
– arousal = awakening from sleep
• stimulation of the RAS – by touch, pressure, pain, light
• no input by olfactory receptors!!
• stimulation of cholinergic neurons that release AcH
– sleep = state of altered consciousness from which you can be arouse
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exact function is still unknown
two components: NREM and REM
NREM – four stages
REM – 3 to 5 episodes per 7 to 8 hour sleep period (10-20 minutes)
regulated by many areas of the brain – hypothalamus, forebrain, medulla oblongata
sleep inducer – adenosine – binds to receptors and inhibits the RAS (inhibits arousal)
caffeine – binds to adenosine receptors and blocks their action – activity of the RAS is maintained
Integrative Functions
• learning and memory
– learning = the ability to acquire new information
• no completely satisfactory explanation
– memory = the process by which information that is acquired through learning is
stored and retrieved
– role for long-term potentiation (LTP) – enhances transmission at the hippocampus
after a period of high-frequency stimulation
– role for glutamate = binds NMDA glutamate receptors on post-synaptic neurons
• different categories of memory
– 1. immediate: ability to recall ongoing experiences, provides perspective to the present time
so we know where we are and what we are doing
– 2. short-term: temporary ability to recall information - seconds to minutes old
» e.g. look up a phone number and then dial it a few seconds later
» hippocampus, mamillary bodies of the hypothalamus and the anterior and medial nuclei
of the thalamus
– 3. long-term: transfer of short-term into a more permanent type
» last from days to years
» e.g. use the telephone number enough – stored permanently
» role for the basal ganglia, cerebral cortex and cerebellum
• http://www.nlm.nih.gov/medlineplus/memory.html
• http://en.wikipedia.org/wiki/Anterograde_amnesia
• http://en.wikipedia.org/wiki/Retrograde_amnesia
Major Regions and Landmarks
• Diencephalon
– includes the hypothalamus, thalamus,
epithalamus and subthalamus
– thalamus: 80% of the diencephalon
• paired oval masses of gray matter
organized into nuclei, interspersed
with white matter
• joined by the intermediate mass
(gray matter) in about 70% of brains
• major relay station for most sensory
impulses from the SC, brain stem
• crude perception of pain, heat and
pressure (refined in cerebrum)
• transmits motor information from
cerebellum to the cerebrum
• relays nerve impulses to and from
different areas of the cerebrum
• seven major groups of nuclei !!!
•hypothalamus
-Emotions, autonomic
functions, hormone production
-mamillary bodies – serve as
relay stations for reflexes
related to eating
-supraoptic and preoptic
nuclei that in hormone
secretion (ADH) and body
temp
-major functions:
1. control of the ANS –
integrates signals from the
ANS (regulated smooth and
cardiac muscle contraction)
major regulator of visceral
activities (heart rate, food
movements, contraction of
bladder)
2. produces hormones &
connects with pituitary to
regulate its activity
3. regulates emotional and behavioral patterns – rage,
aggression, pain and pleasure + sexual arousal
4. regulates eating & drinking – hypothalamus contains
a thirst center which responds to a rise in osmotic
pressure in the ECF (dehydration)
5. controls body temperature – monitors temp of blood
flowing through the hypothalamus
•epithalamus – consists of the pineal gland and habenular nuclei
-pineal gland – part of the endocrine system
-secretes the hormone melatonin
-increased secretion in dark
-promote sleepiness and helps set the circadian
rhythms of the body (awake/sleep period)
•subthalamus – works with the cerebrum and cerebellum to control body
movements
-majority is made of the subthamic nuclei
-sends efferent connections to the caudate nucleus and putamen,
to the medial and lateral nuclei of the thalamus and to the red
nucleus and substantia nigra of the midbrain
-also receives afferent connections from the substantia nigra
Major Regions and Landmarks
BRAIN STEM
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Medulla oblongata
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continuation of the SC that forms the inferior part of
the brain stem
relays sensory information and controls automatic
motor functions
where the SC and MO meet - 90% of the axons from
the right side of the SC cross over to the left side of the
MO and vice versa = decussation
white matter contains sensory/ascending and
motor/descending tracts
some of the white matter form bulges called pyramids
– white tracts that connect the cerebrum to the SC
contains several nuclei also that regulate autonomic
functions - reflex centers for regulating heartbeat and
BP (cardiovascular center), respiration (respiratory
center), plus vomiting, coughing, sneezing, hiccuping
and swallowing
nuclei in the posterior part are associated with
sensations of touch, proprioception, pressure and
vibration
-associated with 5 pairs of
cranial nerves
VIII
IX
X
XI
XII
-other nuclei
1. inferior olivary: part of the
olive
-relay impulses from proprioceptors
to the cerebellum – joint and muscle
position
2. gracile: ascending sensory tracts
from SC synapse here
-relayed to the thalamus by
postsynaptic neurons
3. cuneate: ascending sensory tracts
from SC synapse here
-relayed to the thalamus by
postsynaptic neurons
-injury to the medulla: hard blow to the
back of the head or upper neck can be
fatal
-damages the medullary rhythmicity
area of the respiratory center (disrupts
pattern of breathing)
-non-fatal injury: paralysis and loss of
sensation, irregular breathing and heart
rate
Major Regions and Landmarks
BRAIN STEM
• Pons
= “bridge”
- e.g. connects brain stem to the cerebrum
via bundles of axons
- superior to the medulla and anterior to the
cerebellum
– consists of nuclei (cell bodies in gray
matter) and tracts
– somatic and visceral motor responses
• Pontine nuclei – control voluntary
movements that originate in the cerebral
cortex and are relayed through the pons
into the cerebellum
• Pneumotaxic area – controls breathing
(with medulla)
• Apneustic area – controls breathing (with
medulla)
Major Regions and Landmarks
BRAIN STEM
• Midbrain (Mesencephalon)
– relay station between the cerebrum and the
spinal cord
– extends from the pons to the diencephalon
– sends motor tracts to the SC, medulla and
pons & conducts sensory tracts to the
thalamus
– anterior portion contains a pair of white
tracts = cerebral peduncles
• conduct impulses from the cerebrum to the
SC, pons and medulla
– posterior portion = tectum
• white matter tracts = cerebellar peduncles
• four round elevations = colliculi
• reflex centers for visual activities (tracking,
scanning) pupillary reflex, shape of the lens
• reflexes that mediate movements of the eyes,
head and neck - the startle reflex
• relays impulses from hearing receptors to the
thalamus
-generates involuntary somatic
motor responses
•release of dopamine from
substantia nigra (nuclei) - loss of
these neurons = Parkinsons
•red nuclei forms synapses with
cerebellum to coordinate muscle
movements
Major Regions and Landmarks
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Cerebellum
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divided into hemisphere with lobes - like
the cerebrum
• anterior and posterior lobes
involuntary motor activities
• evaluates and coordinates motor
activities initiated by the cerebrum and
corrects problems by sending info back
to the cerebrum
• regulate posture & balance
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has a superficial layer of gray matter called
the cerebellar cortex - like the brain
deep to the gray matter are tracts of white
matter = arbor vitae
also has nuclei = cerebellar nuclei (origin
of neurons that connect the cerebellum to
the brain and SC)
connected to the brain stem by three
cerebellar peduncles
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inferior – sensory information from the
inner ear and body proprioceptors
middle – carry commands for voluntary
movements that originated into the cortex
into the cerebellum for coordination
superior – connects to the red nuclei and
the nuclei of the thalamus
Medical application: Ataxia
• damage to the cerebellum
• blindfolded people cannot find the tip of
their nose
• also changed speech patterns due to
incoordinate speech muscles
• abnormal walking or balance
• alcohol overdose also suppresses the
activity of the cerebellum
The Limbic System
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corpus
called the emotional brain
callosum
group of structures that surround the brain
cingulate gyrus
stem
anterior thalmic nuclei
hypothalmic nuclei
involved in olfaction and memory
fornix
emotion – anger, fear, happiness…
– associated with specific responses –
behavioral patterns
basic behavioral patterns
– -preparing for attack, laughing,
crying, blushing
– also includes sexual behaviors for
the continuation of the species
– connects with the hypothalamus to
regulate these behaviors
olfactory tract
main components:
mamillary body
– 1. limbic lobe: rim of cerebral cortex
on the medial surface of
amygdala
each hemisphere – includes the
parahippocampal gyrus
hippocampus
hippocampus (memory)
– 2. dentate gyrus
– 3. amygdala: stimulation - rage
– 4. olfactory bulbs
– 5. septal nuclei
– 6. mammillary bodies of the
hypothalamus
Medical Application: Alzheimer’s Disease
-loss or reasoning, memory
-11% of population over 65 (4 million people)
-unknown cause – thought to be genetic factors + environmental &
lifestyle
-neuronal plasma membranes contain a protein = amyloid precursor protein (APP)
abundant in presynaptic axon terminals
-cleavage of APP yields a secreted product = sAPPa that is secreted by the
presynaptic terminals normally
-if APP is cleaved at the wrong site – beta-amyloid
-two forms of beta-amyloid are possible based on cleavage site – the longer
form (Ab40) is harmless
-but the form Ab42 – 10% of the cleaved b-amyloid – aggregates to form
plaques and is neurotoxic
-underlying causes for Ab plaque formation remain unknown
-about 15% of cases appear to have a genetic link – familial Alzheimer’s
-mutations in 3 genes: prenisilin-1, -2 and APP lead to early onset forms
(less the 15% of all cases) – prenisilins cleave APP
-mutations in these genes can shift the balance of b-amyloid to the harmful form,
-so can age
-also mutations in gene coding for apolipoprotein E (ApoE) a protein that helps transport
cholesterol in the blood
-may account for 85% of the cases – late-onset Alzheimers
-mutated genes for apoE = apoE4 – may increase risk of development
-may predispose you to Ab plaque formation, or may hasten the onset - ?????
Medical Application: Alzheimer’s Disease
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-brain abnormalities:
1. loss of ACh releasing neurons from the nucleus basalis (below
the globus pallidus)
2. beta-amyloid plaques
3. neurofibrillary tangles
-plaque – central core of b-amyloid, surrounded by degenerating nerve endings
– the plaques attract microglia – inflammatory reaction against the plaque, including the
secretion of toxic chemicals that harm “bystander” neurons
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-tangles – bundles of abnormal filaments that accumulate in the cell
bodies of the affected neurons
– probably form in response to the formation of Ab plaques – bind to the neurons and alter
the proper formation of the neurons cytoskeleton – production of tangles
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the Ab plaques are also thought to lead to excessive influx of Ca ions which kills the
cells
– hippocampal neurons (long-term memory) seem to be vulnerable
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-treatments: drugs that inhibit acetylcholinesterase improve alertness by increasing
Ach signaling in the brain
e.g. Donepezil – only ones currently approved (Aricept)
– may improve the symptoms – they don’t slow the degeneration
http://en.wikipedia.org/wiki/Alzheimer#Acetylcholinesterase_inhibitors
I - Olfactory
II - Optic
III - Oculomotor
IV-Trochlear
V - Trigeminal
VI - Abducens
VII - Facial
VIII - Acoustic
IX - Glossopharyngeal
X - Vagus
XI - Accessory
XII - Hypoglossal
-cranial nerves – 12 pairs
-considered part of the peripheral nervous system (PNS)
-olfactory & optic contain only sensory axons = sensory nerves
-remaining are either motor or mixed nerves – both motor and sensory axons
“some say my mother bought my brother some bad beer, my my”
Spinal Cord
• length in adults = 16 to 18 inches
• Cervical and lumbar
enlargements
– cervical = C4 to T1, nerves to and
from upper limbs
– lumbar = T9 to T12, nerves to and
from lower limbs
• Tapers to conus medullaris
• filium terminale arises from the
CM - extension of the pia mater that
anchors the SC to the coccyx
• 31 segments each with
– Dorsal root ganglia
• Sensory neuron cell bodies
– Pair of dorsal roots
– Pair of ventral roots
Spinal Meninges
• Specialized membranes
• Provide physical stability and shock absorption
• Three layers
– Dura mater = dense irregular CT
• continuous with the brain’s DM
• above it is the epidural space
– Arachnoid = continuous with brain
• above it is the subdural space
• below is the subarachnoid space
• avascular
– Pia mater = connective tissue
• collagen and elastin bundles
• well vascularized
• The Pia Mater
– Innermost meningeal layer
– Bound firmly to underlying tissue
– Denticulate ligaments bind pia mater to the arachnoid
-spinal tap: under local anesthetic
-long needle is inserted into the
subarachnoid space and CSF is
withdrawn or antibiotics or
anesthetics are given
-given between L3 & L4 or
L4 & L5
Histology of the Spinal Cord
• Central gray matter
– Contains cell bodies of
neurons and glial cells +
unmyelinated axons
– Gray matter projections are
horns
• Peripheral white matter
– Myelinated and
unmyelinated axons
– Tracts or columns
Organization of Gray Matter
• Posterior gray horns
– Somatic and visceral
sensory nuclei
• Anterior gray horns
– Somatic motor control
• Lateral gray horns
– Visceral motor neurons
• Gray commissures
– Axons of interneurons
crossing cordated and
unmyelinated axons
Organization of White Matter
• Six columns (funiculi)
– Anterior, lateral and posterior
white columns
– Contain tracts
• Ascending tracts relay
information from spinal cord
to brain
• Descending tracts carry
information in the opposite
direction
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Spinothalamic tract
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Posterior columns
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pain, temperature, deep pressure &
crude touch
proprioception, discriminative touch,
two-point discrimination, pressure and
vibration
Direct pathways (corticospinal &
corticobulbar)
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precise, voluntary movements
corticobulbar: cerebral cortex to brain
stem and out via cranial nerves to
muscles of head and neck
corticospinal: also called the pyramidal
tracts (lateral and anterior)
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cerebral cortex to spinal cord and out to
voluntary muscles (synapses with lower
motor neurons in the ventral gray horn)
Indirect pathways (rubrospinal,
vestibulospinal)
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programming automatic movements,
posture & muscle tone, equilibrium &
coordination of visual reflexes
rubrospinal: alternate route for
voluntary movements of arms and legs
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red nucleus of midbrain through the
lateral column
vestibulospinal: