Transcript Biosc_48_Chapter_8_lecture_part_1

Chapter 08
CNS
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I. Structural Organization of
the Brain
Central Nervous System

Composed of the brain and spinal cord
a. Receives input from sensory neurons and
directs activity of motor neurons that innervate
muscles and glands
b. Association neurons integrate sensory
information and help direct the appropriate
response to maintain homeostasis and respond
to the environment.
Central Nervous System
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Gyrus
Sulcus
Corpus
callosum
Cerebrum
Meninges
Spinal cord
Central canal
Tentorium
cerebelli
Cerebellum
Embryonic Development
1. From the ectoderm comes a groove that will
become the neural tube around 20 days after
conception. This will eventually become the CNS.
2. Between the neural tube and the developing
epidermis, a neural crest forms. This will become
PNS ganglia.
Embryonic Development of the CNS
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Neural crest
Neural groove
Neural crest
Cranial neuropore
Neural canal
Neural tube
Caudal neuropore
Neural crest
Neural groove
Neural groove
Neural crest
Waldrop
Wall of
yolk sac
Embryonic Development
3. By week 4 after conception, three distinct swellings
are seen on the neural tube:
a. Prosencephalon (forebrain)
b. Mesencephalon (midbrain)
c. Rhombencephalon (hindbrain)
Embryonic Development
4. By week 5, these regions differentiate into five
regions.
a. The prosencephalon divides into the
telencephalon and diencephalon.
b. The mesencephalon remains the
mesencephalon
c. The rhombencephalon divides into the
metencephalon and myelencephalon.
Developmental Sequence of the Brain
Weeks 4 and 5
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Three primary vesicles
Wall
Five secondary vesicles Adult derivatives of
Walls
Cavities
Cavity
Telencephalon
Prosencephalon
(forebrain)
Mesencephalon
(midbrain)
Diencephalon
Mesencephalon
Cerebral
hemisphere
Thalamus
Hypothalamus
Lateral
ventricles
Midbrain
Aqueduct
Pons
Rhombencephalon
Metencephalon
(hindbrain)
Third
ventricle
Upper
portion
Cerebellum
Myelencephalon
Medulla
oblongata
Spinal cord
of fourth
ventricle
Lower
portion
Later development
a. Telencephalon  two cerebral hemispheres and
the two lateral ventricles (remnant of the tube)
b. Diencephalon  the thalamus, hypothalamus,
and the third ventricle
c. Mesencephalon  the midbrain and cerebral
aqueduct
d. Metencephalon  the pons, cerebellum, and
upper fourth ventricle
e. Myelencephalon  the medulla oblongata and
lower fourth ventricle
f. The posterior neural tube becomes the spinal cord
Choroid plexuses and cerebrospinal fluid




Consists of simple cuboidal to columnar epithelium
(ependymal cells) in close association with blood
capillaries
Project into the roofs of the ventricles
Secrete cerebrospinal fluid (CSF) into the
ventricles and central canal of the cord.
CSF is an ultrafiltrate of blood and is returned to
blood
Ventricle of the Brain
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Lateral ventricle
Interventricular
foramen
Lateral ventricle
Third ventricle
Third ventricle
Interventricular
foramen
Mesencephalic
aqueduct
Mesencephalic
aqueduct
Fourth ventricle
Fourth ventricle
(a)
To central canal
of spinal cord
(b)
To central canal
of spinal cord
Brain statistics
1. Gray matter forms the cortex and deep nuclei;
white matter is deep forming tracts
2. The adult brain has 100 billion neurons.
3. It weighs about 1.5 kg (3−3.5 pounds).
4. It receives 15% of the total blood flow to the body
per minute.
5. Scientists have demonstrated neurogenesis (the
formation of new brain cells from neural stem cells)
in adult brains within the subgranular zone of the
hippocampus and subventricular zone of the
lateral ventricles
II. The Cerebrum
Introduction
1.
2.
3.
4.
Derived from the telencephalon
Largest portion of the brain - 80% of the mass
Responsible for higher mental functions
Consists of a right and left cerebral hemisphere
connected internally by the corpus callosum
Cerebral Cortex
1. The outer region of the cerebrum composed of
2−4 mm gray matter with underlying white matter.
2. Characterized by raised folds called gyri
separated by depressed grooves called sulci;
together called convolutions
3. Each hemisphere is divided by deep sulci or
fissures into 5 lobes - Frontal , Parietal,
Temporal, Occipital, Insula
Lobes of the Cerebrum
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Precentral gyrus
Superior frontal
gyrus
Superior
frontal
sulcus
Frontal poles
Central
sulcus
Superior
frontal gyrus
Postcentral
gyrus
Parietal lobe
Central
sulcus
Frontal
lobe
Lateral sulcus
Superior
frontal
sulcus
Longitudinal
fissure
Occipital
lobe
Temporal lobe
Parietal
lobe
Cerebellar
hemisphere
Occipital poles
(a)
(b)
Frontal and Parietal Lobes



Separated by the central sulcus
The precentral gyrus (primary motor cortex) is
located in the frontal lobe and is responsible for
motor control; neurons called upper motor
neurons
The postcentral gyrus (primary somatosensory
cortex) is in the parietal lobe and is responsible for
somatosensory sensations (coming from receptors
in the skin, muscles, tendons, and joints)
Maps of the Precentral and Postcentral Gyri
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“Homunculus”
Central sulcus
Somatosensory cortex
Motor cortex
Thumb,
fingers,
and hand
Lower
arm
Facial
expression
Upper
arm
Upper
leg
Trunk
Lower
leg
Pelvis
Pelvis Trunk Neck
Upper
arm Lower
arm
Hand, fingers,
and thumb
Upper leg
Salivation
Vocalization
Mastication
Lower leg
Foot
and toes
Foot
and toes
Genitals
Upper
face
Lips
Teeth
and gums
Swallowing
Tongue
and pharynx
Longitudinal
fissure
Insula
Insula
Parietal lobes
Central sulcus
Motor cortex
Somatosensory cortex
Frontal lobes
(a)
(b)
Temporal, Occipital, and Insula Lobes



Temporal lobe: auditory centers
Occipital lobe: vision and coordination of eye
movements
Insula: encoding of memory and integration of
sensory information with visceral responses;
receives olfactory, gustatory, auditory, and pain
information
Functional Regions of the Cerebrum
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Central sulcus
Primary motor cortex involved
with the control of voluntary
muscles
Somatosensory cortex for
cutaneous and
proprioceptive senses
Frontal lobe
Parietal lobe
Motor speech area
(Broca’s area)
General
interpretive area
Auditory area
Lateral sulcus
Occipital lobe
Interpretation of sensory
experiences, memory of
visual and auditory patterns
Combining visual images,
visual recognition of objects
Cerebellum
Temporal
lobe
Brain stem
Functions of the Cerebral Lobes
Mirror Neurons





Found in frontal and parietal lobes to integrate
sensory and motor neural activity
Becomes active during goal-directed actions or
through observation of someone else performing
such actions
Connected through the insula and cingulate gyrus
to emotion centers in the brain
May be involved in the ability to learn social skills
and language
Have been implicated in autism (autism spectrum
disorder)
Visualizing the Brain

X-ray computed tomography (CT): looks at soft
tissue absorption of X-rays
 Positron emission tomography (PET):
radioactively labeled fluoro-deoxyglucose
injected into the blood; emits gamma rays in
active tissues
1) Used to monitor cancer
2) Used to study brain metabolism, drug
distribution in the brain, and changes in
blood flow following activity
Visualizing the Brain

Magnetic resonance imaging (MRI): Protons in
tissues are aligned by powerful magnets. The
chemical composition of different tissues results in
differences in proton alignment.
1) Can be amplified using MRI contrast agents
injected before imaging
2) Shows clear definition between gray matter,
white matter, and cerebrospinal fluid
Visualizing the Brain: MRI
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Lateral
ventricle
Third
ventricle
White
matter of
cerebrum
Gray
matter of
cerebrum
Courtesy of Dr. Llinas, New York University Medical Center
Visualizing the Brain

Functional magnetic resonance imaging (fMRI):
visualizes increased neuronal activity in different
brain regions indirectly by looking at blood flow
1) Release of the neurotransmitter glutamate
increases vasodilation of blood vessels in the
area.
2) Active brain regions receive more
oxyhemoglobin; called the BOLD response for
blood oxygenation level dependent contrast
Visualizing the brain

Magnetoencephalogram (MEG)
1) Based on magnetic fields produced by
postsynaptic currents
2) Sensors are SQUIDS – superconducting
quantum interference devices
3) More accurate than EEGs
Visualizing the Brain

Electroencephalogram (EEG): Electrodes on the
scalp detect synaptic potentials produced by cell
bodies and dendrites in the cerebral cortex.
Visualizing the Brain

Four patterns are usually seen:
a) Alpha waves (10-12 cycles/sec): active,
relaxed brain. Best recorded from parietal
lobes and occipital lobe.
b) Beta waves (13-25 cycles/sec): produced with
visual stimulation and mental activity. Best
recorded from frontal lobe.
c) Theta waves (5-8 cycles/sec): seen in sleep
or stress; occipital and temporal lobes
d) Delta waves (1-5 cycles/sec): seen in sleep of
adults and in awake infants
EEG Wave Patterns
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Alpha
Beta
Theta
Delta
1 sec
Techniques for Visualizing Brain Function
Sleep


May be genetically controlled, although sleep is
affected by environmental factors
Neurotransmitters involved
 Histamine – wakefulness
 Adenosine & GABA – sleep
 Serotonin – reduces REM sleep and
stimulates non-REM sleep
Sleep

Two recognized categories:
1) REM (rapid eye movement): state when
dreams occur. Activities similar to Beta waves
are seen here.
2) Non-REM (resting sleep): divided into four
stages, determined by EEG waves seen.
Stages 3 and 4 are often called slow-wave
sleep, characterized by delta waves.
Sleep pattern
1) When people first fall asleep, they enter non-REM
sleep and progress through the four stages.
2) Next, a person ascends back up the stages of nonREM sleep to REM sleep.
3) This cycle repeats every 90 minutes, and most
people go through five per night.
4) If allowed to awaken naturally, people usually do
so during REM sleep.
5) Slow-wave is prominent in the first part of sleep,
while REM is prominent in the second half
Sleep pattern
REM Sleep




Brain waves during REM similar to beta waves.
The limbic system (involved in emotion) is very
active during REM sleep.
Breathing and heart rate may be very irregular.
Benefits consolidation of nondeclarative
memories
Non-REM Sleep




As you fall asleep, neurons decrease their firing
rates, decreasing blood flow and energy
metabolism.
Breathing and heart rate are very regular.
Non-REM sleep may allow repair of metabolic
damage done to cells by free radicals and allows
time for the neuroplasticity mechanisms needed to
store memories.
Benefits consolidation of spatial and
declarative memories
Basal Nuclei

Masses of gray matter located deep in the white
matter of the cerebrum
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Motor cerebral cortex
Thalamus
Claustrum
Putamen
Basal nuclei
Lentiform
nucleus
Globus
pallidus
Corpus
striatum
Caudate
nucleus
Cerebellum
Spinal cord
Basal Nuclei



Most prominent is the corpus striatum; composed
of:
a. Caudate nucleus
b. Lentiform nucleus; made up of the putamen
and the globus pallidus
Also includes subthalamic nucleus of the
diencephalon and substantia nigra of the midbrain
Degeneration of dopaminergic neurons from the
substantia nigra to the corpus striatum causes
Parkinson’s disease
Motor circuit
a. Neurons from motor cortex sends axons to the
striatum (caudate and putamen)
b. Striatum sends axons to the globus pallidus
c. Globus pallidus sends axons to the thalamus
d. Thalamus sends axons to the motor cortex
 This completes a motor circuit. This circuit
stimulates appropriate movements and inhibits
unwanted movement.
 Neurons in the nigrostiatal tract (substantia nigra
 striatum) secretes dopamine, which excites the
direct pathway and inhibits the indirect pathway
Motor circuit – Direct Pathway
Motor Cortex
(+)
(+++)
Muscle
Glutamate
Glutamate
Thalamus
(+)
↓ GABA
(+)
Striatum
(caudate and putamen)
(+)
GABA
(-)
Globus pallidus
(interna)
Dopamine
Substantia nigra
Direct pathway “turns
up” motor activity
Motor circuit – Indirect Pathway
(- - -)
Motor Cortex
(-)
Muscle
Glutamate
Thalamus
Glutamate
(-)
GABA
Indirect pathway
“turns down”
motor activity
Globus pallidus
(+)
(interna)
Striatum
(+)
(caudate and putamen)
Glutamate
(-)
Dopamine
Substantia nigra
GABA
(-)
Subthalamic nuclei
(+)
↓ GABA
Globus pallidus
(externa)
The Motor Circuit
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Glutamate neurotransmitter
(excitatory)
Caudate
Dopamine neurotransmitter
(excitatory)
Putamen
GABA neurotransmitter
(inhibitory)
Thalamus
Globus pallidus
Subthalamic
nucleus
Substantia nigra
Cerebral Lateralization



Each side of the precentral gyrus controls
movements on the contralateral (opposite) side of
the body due to decussation of fibers.
Somatesthetic sensation from each side of the
body projects to contralateral sides of the
postcentral gyrus.
Communication between the sides occurs through
the corpus callosum; this is severed in severe
forms of epilepsy.
Cerebral Lateralization (Dominance)

Some tasks seem to be performed better by one
side of the brain than the other.
a. Right hemisphere: visuospatial tasks,
recognizing faces, composing music,
arranging blocks, reading maps
b. Left hemisphere: Language, speech, writing,
calculations, understand music
Cerebral Lateralization
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Olfaction
Olfaction
Speech, writing
Left ear
Right ear
Simple
language
comprehension
Main language
center
Spatial
concepts
Calculation
Left visual
half
field
Right visual
half
field
Split
brain
Language
1. Most of the knowledge of how the brain controls
language has come from studying people with
speech problems called aphasias.
2. Two areas are identified as important :
a. Broca’s area
b. Wernicke’s area
Broca’s Area



Located in left inferior frontal gyrus
Controls motor aspects of speech
Broca’s aphasia involves slow, poorly articulated
speech. There is NO impairment in understanding.
 Interestingly, other actions of the tongue, lips,
and larynx are not affected; only the production
of speech is affected.
Wernicke’s Area




Located in left superior temporal gyrus, left anterior
occipital lobe and left inferior parietal lobe
Controls understanding of words.
Information about written words is sent by the
occipital lobe (visual cortex).
Wernicke’s aphasia involves production of rapid
speech with no meaning, called “word salad.”
Language (spoken and written) comprehension is
destroyed.
Speech

To speak, word comprehension originates in
Wernicke’s area and is sent to Broca’s area
along the arcuate fasciculus (association fibers).

Broca’s area sends information to the motor
cortex to direct movement of appropriate muscles.
Speech
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Motor cortex
(precentral gyrus)
Motor speech area
(Broca’s area)
Wernicke’s
area
The Limbic System

Group of brain regions responsible for emotional
drives
 Areas of the cerebrum included: cingulate
gyrus, amygdala, hippocampus, septal nuclei,
anterior insula
 The hypothalamus and thalamus (in the
diencephalon) are also part of this system
The Limbic System

Papez circuit
a. The fornix connects the hippocampus to the
mammillary bodies of the hypothalamus, which
sends neurons to the thalamus.
b. The thalamus sends
neurons to the
cingulate gyrus, which
sends neurons to the
hippocampus,
completing the circuit.
The Limbic System
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Corpus
callosum
Thalamus
Cingulate
gyrus
Fornix
Mammillary
body
Septal
nucleus
Amygdala
Preoptic
nucleus
Hippocampus
Olfactory bulb
Olfactory tract
Cortex of right
hemisphere
Hypothalamus
Limbic System

Once called the rhinencephalon, or “smell brain,”
because it has direct connection with olfaction.

There are few synaptic connections between the
limbic system and the cerebral cortex, which is
why it is hard to control your emotions.
Limbic System

Emotions controlled by the limbic system:
 Aggression: areas in the amygdala and
hypothalamus
 Fear: amygdala and hypothalamus
 Hunger/satiety: hypothalamus
 Sex drive: the whole system
 Goal-directed behaviors: hypothalamus
and other regions
Memory
Brain areas involved:
a. Studies of people with amnesia reveal that
areas of the temporal lobe, hippocampus,
caudate nucleus, and dorsomedial thalamus are
involved in memory.
b. The amygdala is important in learning fear
responses.
c. The prefrontal cortex may be involved in
complex problem solving and working memory–
very short-term memory.
Brain areas
d. Left inferior frontal lobe – mathematical
calculations
e. Hippocampus is the critical component
1) Acquire new information
2) Consolidation of short-term memory to longterm memory
f. Inferior temporal lobe – storage of long-term
visual memories
Types of Memory

Short-term memory: recent events; transferred
to long-term memory through process of memory
consolidation
1) Memory consolidation occurs in the medial
temporal lobe, hippocampus, and amygdala.
2) Sleep is needed for optimum memory
consolidation.
Long-term memory

Requires actual structural change - Activation of
genes, synthesis of mRNA, production of proteins,
and formation of new synapses
 Long-term memory can be classified into:
a) Nondeclarative (implicit): memory of simple
skills, how to do things
b) Declarative (explicit): memory of things that
can be verbalized. People with amnesia have
impaired declarative memory; further broken into:
1) Semantic: facts
2) Episodic: events
Categories of Memory
Synaptic Changes in Memory


Short-term memory involves a recurrent circuit
(reverberating circuit) where neurons synapse
on each other in a circle.
 Interruption of the circuit destroys the
memory because there was no structural
change.
Long-term memory requires a relatively
permanent change in neuron chemical structure
and synapses.
Synaptic Changes in Memory – LTP

Long-term potentiation (LTP) in the
hippocampus is a good example.
1) Synapses that are stimulated at a high
frequency exhibit increased excitability.
2) In these synapses, glutamate is secreted by
the presynaptic neuron.
3) The postsynaptic neuron has both AMPA
and NMDA receptors for glutamate.
4) Glutamate binds to AMPA receptor, allowing
Na+ in.
Synaptic Changes in Memory – LTP
5) This depolarizes the cell and activates NMDA
receptor channels (which were inactive due to a
Mg2+ blocking the pore).
6) NMDA allows Ca2+ and Na+ in.
7) The Ca2+ binds to a protein called calmodulin,
which in turn activates an enzyme called CaMKII.
8) CaMKII causes more AMPA receptors to fuse to
the plasma membrane. This alone strengthens the
synapse–it becomes more sensitive to glutamate
release (EPSP).
Synaptic Changes in Memory – LTP
9) Rise in Ca2+ also causes long-term changes in
postsynaptic neurons
a) Ca2+ enters the nucleus and binds to calmodulin
b) Activates protein kinase that activates a
transcription factor called CREB (cyclic AMP
response element binding) protein
c) Activates genes to produce mRNA and
proteins, including dendritic spines with
AMPA receptors inserted.
Synaptic Changes in Memory – LTP
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(a)
(b)
(both): Reprinted from Esther A. Nimchinsky, Bernardo L. Sabatini, and Karel Svoboda, “Structure and Function of Dendritic Spines,”
Annual Review of Physiology, Volume 64: 313–353 © 2002 by Annual Reviews, www.annualreviews.org
Synaptic Changes in Memory – LTP
d. A retrograde messenger (likely NO) is released
into the synapse, and cause presynaptic axon to
change and release more glutamate, which
increase LTP
e. Endocannabinoids may lift inhibition from GABAreleasing neurons on the synapse, further
strengthening it.
Synaptic Changes in Memory
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Presynaptic axon
Glutamate
4. Increased release
of glutamate from
presynaptic axon
AMPA
receptor
Na+
Na+
Ca2+
3. Increased Na+
diffusion through
more AMPA
receptors
1. Glutamate binds to
AMPA and NMDA
receptors
NMDA
receptor
Postsynaptic membrane
of dendrite
CaMKII
Nitric
LTP
Ca2+
oxide
induction
as retrograde
messenger
2. Ca2+ goes through
NMDA receptors into
cytoplasm, activates
CaMKII
Alzheimer’s Disease


Most common form of dementia
Characteristics
1) Loss of cholinergic fibers in hippocampus and
cerebral cortex
2) Accumulation of extracellular proteins called
senile plaques
3) Accumulation of intracellular proteins forming
neurofibrillary tangles
Alzheimer’s Disease

Amyloid precursor protein (APP) is broken down
into peptides called amyloid beta (Aβ)
1) Aβ forms dimers and oligomers that join to form
the fibers in the β-pleated sheet structure that
forms the amyloid senile plaques
2) Soluble dimers and oligomers of the 42-amino
acid form of Aβ causes Alzheimer’s
3) Forms 1% of early onset Alzheimer’s have a
mutation in the APP gene or the presenilin
gene; most have “sporadic” form with
environmental and genetic interactions
Alzheimer’s Disease

Tau protein
1) Normal tau proteins bind to and stabilize
microtubules in axons
2) In Alzheimer’s, they aggregate and become
insoluble forming the neurofibrillary tangles
3) Soluble, intermediate tau proteins are more
toxic
Alzheimer’s Disease
Toxic changes in Alzheimer’s Disease
1) Loss of synapses and dendritic spines
2) Reduced LTP
3) Reduced excitotoxicity leading to neuron
apoptosis
4) Mitochondrial release of reactive oxygen
species causing oxidative stress and apoptosis
 People with APOe4 gene have an increased
chance of developing Alzheimer’s
Current treatments
1)
2)
3)
4)
Acetylcholinesterase inhibitors
Antagonists of glutamate
Drugs for depression
Many others are in clinical trials
Neural Stem Cells in Learning
a. Neural stem cells have been found in the
hippocampus, and scientists suspect that
neurogenesis is part of learning.
b. In mice, physical activity and an enriched
environment promote neurogenesis.
c. Aging and stress reduce neurogenesis.
Emotions and Memory

Emotions sometimes strengthen and other times
weaken memory formation.
a. If the memory has an emotional component, the
amygdala is involved in memory formation.
b. Stress impairs memory consolidation in the
hippocampus and working memory function of
the prefrontal cortex.
c. Posttraumatic stress disorder may result in
hippocampal atrophy.
d. Memories are stored but retrieval is hindered
Emotions and Memory

The amygdala and hippocampus have
receptors for stress hormones, such as
cortisol.
 It is thought that cortisol may strengthen
emotional memory formation via the
amygdala but weaken hippocampal
memory formation and memory retrieval.
Brain Regions Involved in Emotion
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(a)
(b)
(both): Reprinted Figure 2 (1st and 3rd panels) with permission from RJ Dolan, “Emotion, Cognition, and Behavior”
Science 298: 1191–1194. Copyright 2002 AAAS
a. Yellow = prefrontal cortex; mint green = cingulate gyrus
b. Purple = insula; mint green = cingulate gyrus; red = amygdala
Prefrontal Cortex

Orbitofrontal region: ability to consciously
experience pleasure and reward; receives input
from all the senses and the limbic system
 Damage here results in severe impulsive
behavior.

Lateral prefrontal area: motivation, sexual
desire, and cognitive functions