Functions of the nervous system
Nervous system consists of • Nerve cells: neuron• Neuroglia: glia
– Microglia: scavenger cells– Oligodentrogliocyte: myelin– Astrocyte: blood-bain barrier
• Fibrous: white matter• Protoplasmic: gray
Morphology of nerve cells
1. Cell body2. Dentrites: 5-73. Axon: 1
– Axon hillock
Function of the dendrites
• Traditional: extensions of the soma
• Recent observation:– Propagable AP formation– Dendritic spines increase
and disappear– Protein synthesis
Nerve fiber types and function
• Erlanger and Gasser: A, B, C
Nerve fiber types and function
• Lloyd and Hunt: I, II, III, IV
Axoplasmic transport
Axoplasmic flow:Anterograde transport (轴浆运输)
Fast transport: granule, vesicle mitochondria (400 mm/d)Slow transport: dissoluble substances (0.5-10 mm/d)
Retrograde transport (逆向运输): material taken up at the ending: (poliomyelitis)
Axoplasmic transport protein
• Fast anterograde transport is mediated by kinesin (驱动蛋白)
• Retrograde transport is mediated by dynein
Trophic effect of nerve
• By release trophic factors• Regulating the metabolism, protein
synthesis• Trophic factors are transported by
axoplasmic flow
Neurotrophins
• Definition: a number of proteins necessary for survival and growth of neurons
• Produced by: – Muscles– Neuronal innervated tissues– Neurons
Identified neurotrophins• Nerve growth factor (NGF)• Brain-derived neurothopic factor (BDNF)• Neurotropin 3,4,5 (NT-3,4,5)• Others:
– Glial cell line-derived neurotropic factor (GDNF)– Ciliary neurotropic factor (CNTF)– Leukemia inhibitory factor– Insulin-like growth factor I– Transforming growth factor– Fibroblast growth factor– Platelet-derived growth factor
Synaptic transmission in CNS
• Synapse• Presynaptic cell• Postsynaptic cell
Types of synapses in CNS• Chemical synapse
– Axosomatic– Axodendritic– Axo-axonal
• Electrical synapse: gap junction
Structure of Chemical Synapse
• Synaptic knob (terminal button)
• Vesicles • Neurotransmitter• Synaptic cleft• Presynaptic membrane• Postsynaptic membrane• Receptors
A
B
Synaptic vesicles
• Small, clear: – ACh, glycine, GABA, glutamate
• Small with a dense core:– Catecholamines
• Large with a dense core:– Neuropeptides
Chemical Synaptic transmission processes
AP reaches Depolarization at presynaptic membrane Ca2+ release Fusion of vesicle and presynaptic membrane Transmitter release Binding to receptor Electrical event on postsynaptic membrane
A
B
Electrical events in postsynaptic neurons
• Excitatory Postsynaptic Potentials (EPSP)• Inhibitory postsynaptic potential (IPSP)
Electrical events in postsynaptic neurons
1. Excitatory Postsynaptic Potentials (EPSP)– Depolarization potential– Begins about 0.5 ms– Peaks at 1-1.5 ms– Excitability ↑– Opens Na+ or Ca2+ ion channels
EPSP
Electrical events in postsynaptic neurons1. Excitatory Postsynaptic Potentials (EPSP)2. Inhibitory postsynaptic potentials (IPSP)
– Hyperpolarization potential– Begins about 0.5 ms– Peaks at 1-1.5 ms
– Excitability ↓– Opens Cl- ion channels
IPSP
Slow Postsynaptic Potentials
• Recorded at: autonomic ganglia, cardiac & smooth muscle, and cortical neurons
• Transmitters: peptides• Latency: 1-5 s, Last: 10-30 min• Slow EPSPs: decreases in K+ conductance• Slow IPSPs: increases in K+ conductance
Generation of the AP in the Postsynaptic Neuron
• A single input does not evoke AP
• Interplay of excitatory and inhibitory activity
• Initial segment: axon, axon hillock
• Propagated in two directions
• Wiping the slate clean
Inhibition at post synaptic neuron IN CNS
• Postsynaptic inhibition• Presynaptic inhibition
Postsynaptic Inhibition
• Inhibitory interneuron• Inhibitory transmitter• IPSP• Types:
– Reciprocal inhibition– Recurrent inhibition
Postsynaptic Inhibition
• Inhibitory interneuron• Inhibitory transmitter• IPSP• Types:
– Reciprocal inhibition– Recurrent inhibition
Presynaptic Inhibition
• Axoaxonal synapse• Transmitter: GABA• Mechanism:
AP in neuron C→GABA release→ Cl- conductance↑→ AP↓→ Ca2+ influx ↓→ Transmitter release ↓→ EPSP↓
A
B
C
Presynaptic Facilitation
• Axoaxonal synapse• Mechanism:
serotonin →cAMP↑ →phosphorylation and close of K+ channels→prolonged AP →prolonged opening of Ca2+ ↑ → Ca2+ influx ↑→transmitter release ↑→EPSP ↑
A
B
C
Summation & Occlusion• Divergence: a neuron
discharges on many neurons
• Convergence: a neuron receives input of many neurons
• Summation:– Spatial – Temporal
• Occlusion:
Synaptic Delay
• 0.5 ms delay
• Determine reflex pathway is monosynaptic or polysynaptic
Characteristics of excitation in CNS
• One-way conduction• Central delay • Summation and occlusion• Excitatory rhythm changes• After discharge• Susceptible to changes of internal
environment• Easier to get fatigue
Chemistry of Transmitters• Chemical transmission: major role in excitatory
transmission• Nerve ending: biological transducer:
Electrical→Chemical →Electrical• Transmitter:
1. Synthetic enzyme system in presynaptic neuron2. Stored in vesicles and released 3. Receptors at postsynaptic membrane4. Inactive mechanism5. Agonist or antagonist
PRINCIPAL NEUROTRANSMITTERSYSTEMS
• Acetylcholine• Norepinephrine & Epinephrine• Serotonin• Histamine• Amino Acids:
– Excitatory Amino Acids: Glutamate & Aspartate– Inhibitory Amino Acids: Gamma-Aminobutyrate
• Opioid Peptides and Other Polypeptides• Gases: NO, CO, H2S
Acetylcholine
Acetylcholine Receptors
• Muscarine receptor (M receptor): end-plate, brain
• Nicotinic cholinergic receptor (N receptor): autonomic ganglia
Receptors for neurotransmitters
• Each ligand has many subtypes of receptors
• Several large families based on structure and function
• Presynaptic & postsynaptic recptors
• Concentrated in postsynaptic area• Prolonged exposure to their ligands
causes unresponsiveness
Reuptake• Back into • Two families of transporter proteins
– 12 transmembrane and cotransports the transmitter with Na+ and Cl–: NE, dopamine, serotonin, GABA, and glycine
– Made up of at least three transporters: glutamate into neurons and astrocytes
• Vesicular monoamine transporters (VMAT1, VMAT2): neurotransmitters from the cytoplasm to synaptic vesicles (reserpine)
Cotransmitters
• Traditional concept: a neuron has only one neurotransmitter (Dale principle)
• Neurotransmitter coexistence:– Catecholamine or serotonin + peptide(Norepinephrine + neuropeptide Y)
Neuromodulation and neuromodulators
• Chemicals synthesized and released by neurons
• Not participate in signal transfer
• Regulating the efficiency of synaptic transmission
• Neuropeptides or steroids
Reflexes
• Reflex: Response to stimulus with the participate of CNS
• Basic unit: reflex arc, 5 parts
Monosynaptic and polysynaptic reflexes
• Stretch reflex
‹#›
Section ⅩFunction of the Nervous
System
By: Ming-Jie Wang
E-Mail: [email protected]
Schedule
§ Today------Central Regulation of Visceral
Function; Neural Basis of Instinctual
Behavior & Emotions
§ Next Friday------Electrical Activity of the
Brain, Sleep and wakefulness; Higher
Functions of the Nervous system
About this lesson
§ Central Regulation of Visceral Function
l The autonomic nervous system
l Brain stem control of Visceral Functions
l Hypothalamus control of Visceral Functions
§ Neural Basis of Instinctual Behavior &
Emotions
l The limbic system and its function
l Emotions
l Motivation & Addiction
l Brain chemistry & Behavior
Chapter 44
Central Regulation of Visceral Function
§ Autonomic Nervous Systeml Sympathetic Division-norepinephrine
l Parasympathetic Division-acetylcholine
§ Brain stem (Medular Oblongata) control of
Visceral Functionl vital centers
§ Hypothalamus control of Visceral Function
l Feeding & Satiety (food intake)
l Water intake
l Body temperature regulation
l Relation to the pituitary gland
l Relation to cyclic phenomena
AUTONOMIC NERVOUS
SYSTEM (ANS)
‹#›
Introduction
The portion of the body nervous system that
controls the visceral functions is called the
autonomic nervous system (ANS). Impulses
initiated in the visceral receptors are relayed
via afferent autonomic pathways to the
central nervous system, integrated within it at
various levels, and transmitted via efferent
pathways to visceral effectors.
Outputs from the central nervous system
§ Somatic nervous system
l Innervate striated skeletal muscles
§ Autonomic nervous system
l Visceral /Vegetative nervous system
l Innervate smooth muscles, cardiac muscles, glands
and secretary epithelia
l Output is diffused
Autonomic Nervous System (ANS)
§ Self-governing
l Functioning independently of the will
(coordinates cardiovascular, respiratory, digestive,
excretory and reproductive systems)
§ Three divisions
l Sympathetic
l Parasympathetic
l Enteric
§ Efferent and afferent neurons
§ Pre- and post-ganglionic neurons
Sympathetic Division
(fiber)
3
Parasympathetic Division
Preganglionic cell bodies in
nuclei of brainstem or
lateral parts of spinal cord
gray matter from S2-S4
l Preganglionic axons
from brainstem pass to
effector through cranial
nerves
l Preganglionic axons
from spinal cord pass
through pelvic nerves to
effector
The postganglionic fiber is short
§ Dual innervation: Both divisions innervate a particular
organ
l Generally have opposite effects
l In some organs only sympathetic innervation
( blood vessels, kidney, sweat glands )
§ Tonic activity
Originate in the tonic activity of the autonomic centers
§ Actions are affected by the physiological status of the
organ
§ Physiological significance
l Sympathetic: prepares the body to meet an
emergency situation
l Parasympathetic: protection, energy reservation
(digestion and absorption)
‹#›
Sympathetic and
parasympathetic
nervous systems
Sympathetic
preganglionic fiber is
usually short, while
parasympathetic
preganglionic fiber is
usually long.
Chemical transmission at autonomic junctions
§ All preganglionic neurons (both divisions) are
cholinergic, they release ACh and stimulate N2 nicotinic
receptors
§ All postganglionic parasympathetic neurons are
cholinergic, they release ACh and stimulate M receptors
on viscera
§ Most postganglionic sympathetic neurons are
noradrenergic, they release norepinephrine onto visceral
targets.l Except: Sympathetics innervating sweat glands and blood
vessels in skeletal muscle (sympathetic vasodilator nerves) are
cholinergic
§ Cotransmitters can be released: ATP, NO, peptide…
ACh AChSweatglands
Striatedmuscle
ACh
SOMATIC NERVOUS SYSTEM
HeartSm. mus.Glands
ACh AChParasympathetic
AChE, NE
Ad. M.
HeartSm. mus.Glands
ACh NE
AUTONOMIC NERVOUS SYSTEM
Sympathetic
Location of ANS Receptors
Somatic and Autonomic Nervous System
Somatic1. Skeletal muscle
2. Conscious and
unconscious movement
3. Skeletal muscle contracts
4. One synapse
5. Acetylcholine
Autonomic1. Smooth and cardiac
muscle and glands
2. Unconscious regulation
3. Target tissues stimulated or inhibited
4. Two synapses
5. Acetycholine by preganglionic neurons and ACh or norepinephrine by postganglionic neurons
Functions of Sympathetic and
Parasympathetic Nervous System
(1)Sympathetic and parasympathetic Nerves
innervate the same organ.
(2) Sympathetic and parasympathetic "tone"
The sympathetic and parasympathetic systems are
continually active, and the basal rates of activity are
known, respectively, as sympathetic tone or
parasympathetic tone.
(3)Effects of regulating visceral by Autonomic
(vegetative) Nervous System are concerned with the
condition of the organs.
‹#›
Responses of effector organs
to autonomic nerve impulses
Acetylcholine
§ Nicotinic receptors
l Nm (muscular-type or N2): skeletal muscle
l Nn (neuron-type, or N1): autonomic ganglia,
CNS
§ Muscarinic receptors
l Postganglionic parasympathetic and a few
sympathetic sites, CNS (also autonomic gang.)
l Receptor subtypes: M1-5
Catecholamines§ Norepinephrine
l Postganglionic sympathetic, CNS, adrenal medulla
l Receptors: a1, a2, b1
§ Epinephrine
l Adrenal medulla, CNS
l Receptors: a1, a2, b1 , b2
§ Dopamine
l Autonomic ganglia, CNS
l Receptors: D(1-5)
Function of ANS
on the target
organs
Effector Sympathetic Parasympathetic
Radialmuscle
Contraction(mydriasis, a1)
—
Sphinctor — Contraction(miosis)
Ciliarymuscle
Slight relaxa-tion (b2)
Contraction (nearvision)
Eye
Cornea
Lens
Ciliary
muscle
Iris
(M)
SA node
Atria
AV node
Ventricles
Heart
Effector Sympathetic Parasympathetic
SA node Tachycardia(b1,b2)
Bradycardia
Atria contractilityand conduction(b1,b2)
contractility,conduction(usually)
AV node conductionand auto-maticity (b1,b2)
conduction
Ventricles contractility,conduction, andautomaticity(b1,b2,a1)
—
Heart
Effector Sympathetic Parasympathetic
Skin andmucosa
Constriction(a1,a2)
Dilation (?)
Skeletalmuscle
Constriction(a), dilation(b2)
—
Salivaryglands
Constriction(a1,a2)
Dilation
Erectiletissue
Constriction(a)
Dilation
Blood vessels
‹#›
Effector Sympathetic Parasympathetic
Bronchialsm. musc.
Relaxation (b2) Constriction
Bronchialglands
(a1),(b2),secretion
secretion
Salivaryglands
Viscous,amylasesecretion(a1,b1,b2)
Profuse waterysecretion
Lungs and salivary glands
Effector Sympathetic Parasympathetic
Smoothmuscle
motility andtone(a1,a2,b1,b2)
motility andtone
Sphincters Contraction(a1)
Relaxation
Secretions secretion (a2) secretion
Liver Glycogenolysis,gluconeogene-sis (a1,b2)
Glycogensynthesis
Gastrointestinal tract and liver
Sympathetic nervous system
§ Sympathetic nervous system prototypically “fight” or
“flight”.
§ Associated with increased
l energy expenditure,
l cardiopulmonary adjustments for intense activity,
l blood flow adjustments for maximum energy expenditure.
§ Tonic noradrenergic discharge to the arterioles
maintains arterial pressure
SNS - Fight & Flight Reaction
You’re walking alone at night and all the sudden you hear
an unfamiliar noise near by… In a matter of seconds, l your heart rate increases dramatically,
l blood vessels in your skeletal muscles dilate,
l blood vessels in the visceral muscles constrict,
l blood vessels in the skin constrict (limits bleeding from
wounds),
l digestion is ceased,
l your liver ramps up glucose release (supplying more
energy),
l your pupils dilate (more light into the eyes),
l salivary production decreases,
l sweat increases.
Autonomic Nervous System
• Cholinergic
• Day-to-day living
• Relaxation, digestion
• Dominated by
Acetylcholine
• Anabolic
• Noradrenergic
• Emergency situations
(Fight & Flight)
• Dominated by
Norepinephrine
(Epinephrine)
• Catabolic
Interactions of the ANS
§ Most visceral organs are innervated by both types of nerves.
§ Most blood vessels are innervated only by sympathetic nerves.
§ PS activity dominates the heart and GI tract.
§ Activation of the sympathetic division causes wide spread, long-lasting mobilization of the fight-or-flight response.
§ PS effects are highly localized and short lived.
‹#›
BRAIN CONTROL OF
VISCERAL FUNCTIONS § Spinal cord is primary center of visceral
activity
§ There are some primary centers of visceral
activity in the spinal cord. Some simple
reflexes are integrated in the spinal cord.
l emptying of full bladder
l defecation
l diaphoresis
l blood vessels tonic contraction
Spinal cord
Medulla oblongata
§ The medullary centers for the autonomic
reflex control of the circulation, heart, and
lungs are vital centers because damage to
them is usually fatal.
§ Swallowing, coughing, sneezing, and
vomiting are also reflex responses
integrated in the medulla oblongata.
Midbrain
§ Center for the pupillary reflex to light and
accommodation
§ A higher center for regulation of visceral functions
— integration of higher cortical and limbic systems
with autonomic control (visceral, somatic, behavior,
emotion)l A prominent example: defense reaction
§ Connections with other brain areasl Limbic forebrain
l Brain stem nuclei
l Spinal cord
The hypothalamusFunctions of Hypothalamus
①Regulation of food intake
②Regulation of body water-balance
③Regulation of body temperature: heat-
sensitive-neurons and cold-sensitive neurons.
④Control of the pituitary gland
⑤Control of biorhythms
⑥Defensive reaction: fear, rage
⑦Other “instinct” behavior : such as sexual
behavior
‹#›
§ Food intake is regulated not only on a meal-to-
meal basis but also in a way that generally
maintains body weight at a given set point
§ Depends on the interaction of two areas:
l Feeding center: lateral hypothalamus
(Bilateral lesions cause anorexia)
l Satiety center: ventromedial hypothalamus
(Bilateral lesions cause overeating and become obese)
1. Role in food intakethalamus
mamillo-thalamic
tract
dorsalhypothalamic
area
dorsomedialnucleus dorsomedial
nucleus
Lesions in ventromedial nucleus
Lesions in lateral hypothalamus
Voracious appetite Loss of appetite
Effects of hypothalamic lesions on feeding
Feeding centerSatiety center
Short-term regulation of Feeding behavior
§ Satiety center functions by inhibiting the feeding
center.
§ The drive to eat is inhibited by satiety signals
which occur during eating and digestion:
l Gastric distension
l Cholecystokinin (CCK) and glucagon, somatostatin
l Insulin
l High glucose utilization (glucose-sensitive neurons
detecting the arteriovenous blood glucose difference)
Long-term regulation of Feeding behavior
§ Lipostatic hypothesis — a mechanism to maintain
energy homeostasis
§ The brain monitors the amount of body fat
§ Communication from adipose tissue to the brain
§ Leptin:
l released by adipocytes (encoded by ob gene)
l regulates body mass by acting on hypothalamus
l Leptin ↑: activate leptin receptors on neurons of arcuate
nucleus, anorectic peptides (αMSH and others) released
and inhibit feeding behavior
l Leptin ↓: stimulate another type of arcuate nucleus
neurons, orexigenic peptides (NPY and orexin) released
and stimulate feeding behavior
ob/ob mouseNormalmouse
Parabiosis
ob/ob mice
§ Lack both copies of ob gene
§ Lack plasma leptin
§ High motivation to eat
§ Obese
§ Treating with leptin completely
reverses obesity and feeding
behavior
§ Parabiosis: an ob/ob mouse is
surgically fused with a normal
mouse (sharing common blood
supply), its feeding behavior and
obesity are reduced
Increased food intake,
decreased energy
expenditure
FAT DEPOTS
Increased fat deposition
Increased leptinsynthesis
HYPOTHALAMUS
Increased activation
of leptin receptors
Increased plasma
leptin concentration
Feedback control of fat depots by leptin
+
+
+
‹#›
Body fluid homeostasis
§ Water intake — thirst, drinking
(vasopressin secretion, PVN, SON)
l Body fluid osmolality — brain osmoreceptors
(organum vasculosum of the laminar terminalis, OVLT)
l Extracellular fluid volume — renin-angiotensin
system involved
(angiotensin Ⅱ SFO thirst drinking)
§ Water excretion — renal collecting duct
2. Role in water intakeRegulation Of Water-Balance
Hypertonic Low volume
3. Role in body temperature regulation
Heat production heat loss
§ The center of regulating body temperature is
located in the hypothalamus.
l Decorticated animal — body temperature stable
l Brain transection below diencephalon
— body temperature unstable
§ Temperature-sensitive neurons in hypothalamus
— Preoptic anterior hypothalamus ( PO/AH )
(body temperature-regulating center)
§ Set point for body temperature control
Regulation of body temperature
4. Relation to the pituitary gland
Hypothalamohypophyseal
tract 下丘脑垂体束 (neural
connection)
Hypophyseal portal system
垂体门脉系统 (vascular
connection)
Control Of Anterior Pituitary Secretion
§ Anterior pituitary secretion is controlled by
chemical agents carried in the portal hypophyseal
vessels from the hypothalamus to the pituitary.
§ There are 6 established hypophysiotropic hormones
(促垂体激素). The releasing hormones can trigger
the anterior pituitary gland releasing, but the
inhibition hormones reduce their releasing.
‹#›
§ Biological rhythms: Many physiological
functions vary in a pattern that repeats itself
daily, monthly or annually.
§ These rhythms appear to be endogenous
because they persist even in the absence of
time cues
§ The hypothalamus is thought to play a major
role in regulating all of these biological
rhythms
5. Relation to cyclic phenomenaCircadian rhythms
§ Circadian rhythms: Most homeostatically
regulated functions exhibit peaks and valleys
of activity that recur approximately daily.
§ Body temperature, sleep-wake cycles and
some hormones release
Suprachiasmatic nucleus (SCN)
§ SCN, a center in the hypothalamus, drives the circadian
rhythms
§ Lesions of the nuclei disrupt circadian rhythm in the
secretion of ACTH and melatonin
§ The nuclei receive input from the eye (retinohypothalamic
fibers)
§ Synchronize various body rhythms to
light-dark cycle
Chapter 45
Neural Basis of Instinctual
Behavior & Emotions
§ The limbic system and its function
§ Emotions
§ Motivation & Addiction
§ Brain Chemistry & Behavior
‹#›
The limbic system
§ A rim of cortical tissue around the hilum of the cerebral
hemisphere and a group of associated deep structures: the
amygdala, hippocampus, and septal nuclei
§ Regulation of visceral functions, emotion, behavior
Instinctual behavior
§ Life-maintaining functions — from millions of
years of evolution
§ Survival of an individual — Eating, drinking
§ Survival of a species — Reproduction, sex-
related behaviors
§ Associated with emotional responses
§ Regulated by hypothalamus and limbic system
Emotions
§ Emotions have both mental and physical
components (involve cognition, affect, conation and
physical changes)
§ Feelings (love, hate, disgust, joy, shame, envy, guilt,
fear, anxiety, ……)
§ Neural basisl Cortex is involved in the experience of emotion
l Hypothalamus governs the behavioral expression
of emotion
l Hypothalamus and cortex link each other
Fear and rage
Klüver-Bucy syndrome — bilateral temporal lobectomy
in monkey has dramatic effect on the animal’s
responses to fearful situations
§ Emotional changes ( an apparent decrease in fear, let the
human stroke them and pick them up, both the normal
experience and expression are severely decreased)
§ Hypermetamorphosis ( irresistible compulsion to examine
things, run around and touch everything and place it in mouth)
§ Altered sexual behavior ( strikingly increased interest in sex)
§ Psychic blindness ( not seem to recognize common objects)
Defense reaction
Stimulation of the medial hypothalamus of a cat —§ Somatic and behavioral responses: growl, hiss, fold ears back,
arched back, hair erection, …… highly coordinated set of
behaviors normally occurs when feels threatened by an enemy
— fight-or-flight response
§ Visceral responses: increase in BP, HR, cardiac output,
pupillary dilatation, muscular vasodilation, splanchnic
vasoconstriction
§ Affective aggression (a threat attack): hiss, spit, arching back,
but would usually not attack the victim (a nearby rat)
§ Predatory aggression (a silent biting attack) by stimulating the
lateral hypothalamus: no dramatic threatening gestures, but
would move swiftly toward a rat and viciously bite its neck
Amazing cases in humans
§ Phineas Gage in 1848: Passage of an iron
rod through the head, Gage was no longer
Gage
§ Surgery to reduce human aggression:l Psychosurgery: early in 20th century
l Electric coagulation of amygdala
l Frontal lobotomy: in 1949 the Nobel Prize
in medicine was awarded to Dr. Egas oniz
for his development of the frontal
lobotomy technique (tens of thousands
were performed lobotomies following
World War Ⅱ, though not being performed
anymore now)
‹#›
Anxiety
§ Mediated by a2 GABAA receptor
§ Relieved by benzodiazepines
Motivation
§ Self-stimulation:
l “Pleasure areas” — septal area,
lateral hypothalamus, the medial
forebrain bundle, ……reward system
l “Displeasure areas” — medial
hypothalamus, lateral midbrain
punishment system
§ Brain stimulation in humans:
l Septal area, caudate nucleus, ……
Patients with intractable pain
§ D3 dopaminergic receptors Self-stimulation
Addiction
§ Associated with the reward system, particularly
with the nucleus accumbens (伏隔核)
§ Mesocortical dopaminergic neurons
§ Increase the amount of dopamine available to act
on D3 receptors in the nucleus accumbens
Brain Chemistry & Behavior
§ Aminergic systems (胺能系统) in the brain
l Serotonin, Norepinephrine, Epinephrine, dopamine
§ Histamine
§ Acetylcholine
l Alzheimer’s disease
§ Opioid peptides
Responses of effector organs to
autonomic nerve impulses
§ Acetylcholine
l N1,2 , M1-5
§ Norepinephrine
l a1, a2, b1
§ Epinephrine
l a1, a2, b1 , b2
Function of ANS on the target organs
§ Eye
§ Heart
§ Blood vessels
§ Lungs and salivary glands
§ Gastrointestinal tract and liver
Medulla oblongata
§ The medullary centers for the autonomic
reflex control of the circulation, heart, and
lungs are vital centers because damage to
them is usually fatal.
§ Swallowing, coughing, sneezing, and
vomiting are also reflex responses
integrated in the medulla oblongata.
Functions of Hypothalamus
①Regulation of food intake
②Regulation of body water-balance
③Regulation of body temperature: heat-
sensitive-neurons and cold-sensitive
neurons.
④Control of the pituitary gland
⑤Control of biorhythms
⑥Defensive reaction: fear, rage
⑦Other ―instinct‖ behavior : such as sexual
behavior
Instinctual behavior
§ Life-maintaining functions — from millions
of years of evolution
§ Survival of an individual — Eating, drinking
§ Survival of a species — Reproduction, sex-
related behaviors
§ Associated with emotional responses
§ Regulated by hypothalamus and limbic
system
Addiction
§ Associated with the reward system, particularly
with the nucleus accumbens (伏隔核)
§ Mesocortical dopaminergic neurons
§ Increase the amount of dopamine available to
act on D3 receptors in the nucleus accumbens
Brain Chemistry & Behavior
§ Aminergic systems (胺能系统) in the brain
l Serotonin, Norepinephrine, Epinephrine,
dopamine
§ Histamine
§ Acetylcholine
l Alzheimer’s disease
§ Opioid peptides
About this lesson§ Electrical Activity of the Brain, Sleep and
wakefulnessl Electrical Activity of the Brain
• Evoked Cortical Potentials
• The Electroencephalogram
l The Reticular Activating System
l Sleep physiology
§ Higher Functions of the Nervous systeml Learning & Memory
• Forms of memory
• Habituation & Sensitization
• Conditioned Reflexes
• Neural Basis of learning and Memory
l Cerebral Dominance and language
Chapter 46
Electrical Activity of the Brain, Sleep and
wakefulness
§ Sleep and wakefulness: circadian
periodicity
§ Universal among higher vertebrates
§ Sleep is a readily reversible state of
reduced responsiveness to and interaction
with the environment. It is an active part of
the normal function of the body.
§ Compare to coma and general anesthesia
ELECTRICAL ACTIVITY OF
THE BRAIN
Electric activity of cerebral cortex
§ Spontaneous electric activity of the brain
l Electroencephalogram (EEG)
l Brain death: a maintained flat EEG
§ Evoked cortical potential
Evoked cortical potential
§ Definition: The electrical events that
occur in the cortex after stimulation of a
sense organ can be monitored.
§ Component:
l Primary response
l Secondary response
l After discharge
Evoked cortical potential
Animal experiment
§ Guinea pig is anesthetized to eliminate
background EEG
§ Stimulation of sciatic nerve
§ Recording electrode on the sensory cortex
§ A latency followed by a positive-negative
wave (primary response)
§ A larger, more prolonged positive deflection
(diffuse secondary response)
latency
primary response
secondary response
after discharge
Somatosensory evoked potential
§ Elicited by stimulation of the
peroneal nerve
§ Component:
Primary response
highly specific in its location
large pyramidal cells
Secondary response
diffuse
activity in projections from the
midline and related thalamic
nuclei
After discharge (cortex-thalamic circuit)
§ Can be used clinically to assess
the integrity of a sensory pathway
Electroencephalogram (EEG)
§ Definition: The record of the variations in potential
recorded from the brain is called the EEG.
§ EEG can be recorded with scalp electrodes through
the unopened skull or with electrodes on or in the
brain. The term electrocorticogram (EcoG) is
sometimes used to refer to the record obtained with
electrodes on the pial surface of the cortex.
§ Used clinically diagnose and localize brain lesions,
tumors, infarcts, infections, abscesses, epileptic
lesions and brain death.
spontaneous
cortical
electrical
potentials
Different waves in EEG
Alpha waves (alpha rhythm)
§ Adult human at rest, eye
closed, mind wandering,
most prominent wave of
EEG
§ Fairly regular
§ Most marked in the
parieto-occipital area
§ Frequency:8-12 cycles/sec
§ Amplitude: 50100 V
Alpha Block
§ α rhythm is replaced by fast, irregular low-voltage
activity when the eyes are open and attention is
focused on something (arithmetic solving) . This
phenomenon is called alpha block.
§ Known as ―arousal‖ or ―alerting response‖
Beta waves (Beta rhythm)
§ Appears during
cortical activity
§ Strongest from
frontal lobes
§ Frequency:18-30
cycles/sec
§ Amplitude: 520 V
Theta waves
§ Emitted from temporal
and occipital lobes
§ Common in newborn,
some in sleep adult
(drowsy states)
§ Adult indicates
emotional stress
§ Frequency:4-7
cycles/sec
§ Amplitude: 100150 V
Delta waves
§ Large, slow waves
§ Common during deep
sleep and awake
infant
§ In awake adult
indicate very serious
brain damage
§ Frequency:0.5-4
cycles/sec
§ Amplitude: 20200 V
Physiological basis of EEG
§ Synchronized activity: neural components
discharge rhythmically
§ Electrical activities of the dendrites of cortical
cells correlate with postsynaptic potential
§ Reverberating activity between cortex and
nonspecific thalamic nuclei
§ EEG arousal: by stimulating the midbrain
ascending reticular activating system (ARAS)
[Lesion of midbrain tegmentum: synchronization,
comatose for long periods]
§ Currents in extracellular space generated by
summation of EPSPs and IPSPs
§ Continuous graph of changing voltage fields at scalp
surface resulting from ongoing synaptic activity in
underlying cortex
§ Inputs from subcortical structures (Thalamus)
EEG Records During
Epileptic Seizure
Epilepsy is characterized by
uncontrolled excessive activity of
either a part or all of the central
nervous system.
Grand mal epilepsy:
characterized by extreme
neuronal discharges in all areas
of the brain, last from a few
seconds to 3 to 4 minutes.
Petit mal epilepsy: Characterized
by 3 to 30 seconds of
unconsciousness or diminished
consciousness during which the
person has several twitch-like
contractions of the muscle.
THE RETICULAR ACTIVATING
SYSTEM
Wakefulness and Sleep
Maintenance of wakefulness§ Stimulation of the ascending reticular activating
system (ARAS): stimulation of the midbrain reticular
formation (RF) causes activation of the cortex and
awakes a sleeping animal
§ Transmitter involvedl acetylcholine (phasic action)
l noradrenergic system (tonic action, Locus ceruleus, 蓝斑)
§ EEG arousalcholinergic system (RF)
§ Behavioral arousaldopamine system (substantia nigra)
黑质
RAS is cut off
SLEEP PHYSIOLOGY
Sleep
§ Sleep is a behavior and an altered state of
consciousness
l Sleep is associated with an urge to lie down for several
hours in a quiet environment
• Few movement occur during sleep (eye movements)
l The nature of consciousness is changed during sleep
• We experience some dreaming during sleep
• We may recall very little of the mental activity that occurred
during sleep
§ We spend about a third of our lives in sleep
l A basic issue is to understand the function of sleep
Importance of Sleep
§ Sleep is necessary for survival
§ Sleep appears necessary for our nervous systems to work properly.
§ During the SWS, growth hormone secretion increase and important for the infants growth and physical restorative process of adult
§ During REM, brain blood flow and protein synthesis increase, and it is important for the mental development of infants and long-term memory and mental restoration in adults.
§ Daily sleep requirements decline with age
What Happens if We are Deprived of Sleep?
§ Lack of alertness
§ Fatigue
§ Memory problems
§ Irritability
§ Depression
§ Lack of motivation
§ Accidents
§ Fibromyalgia
Two types of sleep
§ Slow wave sleep (SWS)/non-REM sleep (NREM):
A person falling asleep first enters this stage, and
passes through four stages of NREM during the
first 30-45 minutes of sleep.
§ Fast wave sleep (FWS) / Rapid eye movement
(REM) sleep: Occurs after the fourth NREM stage
has been achieved. Back-and-forth movements of
the eyes under closed lids, accompanied by
autonomic excitation.
l Dreams occur
l EEG activity is rapid (paradoxical sleep)
Slow wave sleep§ EEG changes as one falls asleep
l Wakefulness: random pattern of fast waves of low voltage
l Quiet restfulness: one closes eyes — α rhythm, sleep
spindles
l Light sleep: replaced by larger and slower waves — θ
rhythm
l Deep slow wave sleep: high voltage δ rhythm
l Thus, EEG waves are slow and synchronized
§ Characteristicl decreased heart rate and blood pressure
l slow and regular breathing
l reduced sensory functions
l reduced muscular tone and reflex activity
l increased growth hormone release
Four stages of SWS
Stage 1eyes are closed and relaxation begins; the EEG shows alpha waves; one can be easily aroused
Stage 2EEG pattern is irregular with sleep spindles (high-voltage wave bursts); arousal is more difficult
EOG
EOG
EMG
CENTRAL
FRONTAL
OCCIP
EOG
EOG
EMG
CENTRAL
FRONTAL
OCCIP
Stage 3
sleep deepens; theta and delta waves appear; vital signs decline; dreaming is common
Stage 4
EEG pattern is dominated by delta waves; skeletal muscles are relaxed; arousal is difficult
EOG
EOG
EMG
CENTRAL
FRONTAL
OCCIP
EOG
EOG
EMG
CENTRAL
FRONTAL
OCCIP
Genesis of slow-wave sleep
§ Stimulation (low frequency of 8/s) of the following
brain areas produces slow-wave sleep
l Diencephalic sleep zone: posterior hypothalamus
l Medullary synchronizing zone: RF at the level of NTS
l Basal forebrain sleep zone: preoptic area, diagonal band
§ Neurotransmitters involved
l SWS: 5-HT (serotonin antagonist increases SWS in
human)
l REM: 5-HT, norepinephrine, Ach
l PGD2 in medial preoptic area increases SWS and REM
§ Humoral factors: Sleep peptide (?)
Chemical Control of Sleep/Waking
§ Sleep is regulated: loss of SWS or REM sleep is made up somewhat on following nightsl Does the body produce a sleep-promoting chemical
during wakefulness or a wakefulness-promoting chemical during sleep?
§ Unlikely that sleep is controlled by circulating chemicals:l Siamese twins share the same circulatory system, but
sleep independently
l Bottle-nose dolphins: the two hemispheres sleep independently
Fast wave sleep/REM Sleep§ Desynchronized EEG pattern ( resembles
wakefulness — beta rhythm)
§ Characteristic
l The autonomic nervous system is in a state of excitation
• Heart-rate quickens, blood pressure increases
• Breathing more irregular and rapid
l further decrease in muscular tone and reflex activity
l Recallable, vivid, emotional dreams
l Physiological arousal threshold increases
§ Mechanism: Pontogeniculo-occipital (PGO) spikes
§ May be involved in memory consolidation.
Important for reinforcing memory traces
REM Dreaming NREM Dreaming
§ ―vivid and exciting‖
§ 3~4 per night
§ Longer, more
detailed
§ Fantasy world
§ ―just thinking‖
§ Shorter, less
active
§ Midst of nowhere
§ Logical, realistic
Normal sleep cycles§ Slow-wave sleep occurs first, passes through
stages 1, 2, 3 and 4 (spends 80~120 min)
§ Sleep then lightens, and a REM sleep follows
(20 ~30 min)
§ This cycle is repeated throughout the night
l 4~6 cycles per night
l Cycles are similar, but less stages 3 and 4, and more
REM sleep towards morning
§ Can be awakened from both slow-wave and
REM sleep
§ The suprachiasmatic and preoptic nuclei of the
hypothalamus regulate the sleep cycle
Children
Young adults
Elderly
awakeREM
1234
awakeREM
1234
awakeREM
1234
1 2 3 4 5 6 7
1 2 3 4 5 6 7
1 2 3 4 5 6 7
Sle
ep st
ag
es
Sle
ep st
ag
es
Sle
ep st
ag
es
Normal sleep cycles at various ages
Percent of total sleep time in
stage 4 sleep
Percent of total sleep time in
REM sleep
Total sleep time
Per
cen
tP
erc
en
tH
r/d
ay
Insomnia:
Sleeping pills (benzodiazepines)
Narcolepsy:
Sleep disorders
§ Frightening dream episodes
§ Occur in the REM stages
§ Last about 20 minutes
§ Can be result of taking drugs that affect neurotransmitter action or from drug withdrawal
§ Severe cases can be treated with medication
Diazepam (tranquilizer)
Nightmares
Tips for Getting a Good Night’s Sleep
§ Avoid caffeine and alcohol after dinner
§ Keep a routine
§ Don’t nap during the day
§ Don’t go to bed hungry or right after
eating
§ Exercise
§ Stop smoking
Chapter 47
Higher Functions of the Nervous
system
LEARNING & MEMORY
Learning & Memory
§ Learning is a process of nervous system
activity to alter behavior and adapt to
environment on the basis of experience .
§ Memory is the ability to the storage of
information and recall past events at the
conscious or unconscious level.
Forms of memory
Declarative (Explicit) or Nondeclarative (Implicit) Memory
§ Declarative (Explicit) -- conscious recall of
events
l Episodic - knowledge of your own past
experiences (events)
l Semantic - general knowledge of the world (words,
rules, language)
§ Nondeclarative (Implicit) -- often totally
unconscious
l learned skills or habitual responses
l Nonassociative (habituation, sensitization)
l Associative (conditioning)
Forms of memory
Declarative (Fact) memory
§ Entails learning explicit information
§ Is related to our conscious thoughts and our language ability
§ Is stored with the context in which it was learned
Nondeclarative (Skill) Memory
§ Skill memory is less conscious than fact
memory and involves motor activity
§ It is acquired through practice
§ Skill memories do not retain the context in
which they were learned
Memory
§ The three principles of memory are:
l Storage – occurs in stages and is continually changing
l Processing –accomplished by the hippocampus and surrounding structures
l Memory traces – chemical or structural changes that encode memory
§ Short-term memory
l Lasts seconds to hours
l it is the memory of a few facts, words, numbers,
letters.
l Memory traces are subject to disruption
l working memory: temporary storage for
seconds, current information
§ Long-term memory
l tertiary memory and secondary memory
l Stores memories for hours, days, months,
years and sometimes for life.
l Memory traces are resistant to disruption
Transfer from STM to LTM
§ Factors that affect transfer of memory from
STM to LTM include:
l Emotional state – we learn best when we are
alert, motivated, and aroused
l Rehearsal – repeating or rehearsing material
enhances memory
l Association – associating new information with
old memories in LTM enhances memory
Simple passage of time after learning has minimal effect on retention
Forgetting as a result of decay?
Forgetting as a result of interference
§ Retroactive Interference
Current learning interferes with recall of
previously learned material
§ Proactive Interference
Prior learning interferes with retention of
new information
Retrograde and Anterograde Amnesia
Time
Retrograde Anterograde
Head Trauma
Forms of learning
§ Nonassociative learning
l Habituation
l Sensitization
§ Associative learning
l Classic conditioning
l Operant conditioning
Nonassociative learning
No paired stimulus/response
§ Habituation - becomes less responsive to
repeated no-harmful stimulus
§ Sensitization - becomes more responsive
to repeated harmful stimulus
Associative learning
Paired stimulus/response
§ classical conditioning (two stimuli are paired,
e.g. when the light shines ----- get food)
§ operant conditioning (stimuli and response
are paired, e.g.push lever = food)
Classic conditioning
§ It is a classical example of associative
learning.
§ Pavlov’s classic experiment
l Unconditioned stimulus (US)
l Conditioned stimulus (CS)
Operant conditioning
(trial-and-error learning)
§ A predictive relationship between response and a
stimulus (must have predictive element)
§ behaviors that are rewarded tend to be repeated;
those that cause aversive consequences are not
repeated
§ timing is important
§ Typical experiment: Animal is taught to perform a
task (pressing a bar) in order to obtain a reward
Conditioned Reflex
§ Definition: A conditioned reflex is reflex
response to a stimulus that previously elicited
little or no response (CS), acquired by
repeatedly pairing the stimulus with another
stimulus that normally does produce the
response (US).
§ Internal inhibition (Extinction) & External
inhibition
§ Form of conditioned reflex
(1)Classical conditioning reflex
(2)Operant conditioned reflex
Elementary Principle of Conditioned Reflex
§ Reinforcement: When unconditioned and
conditioned stimuli are applied in the correct
temporal sequence for a sufficient number of
times, ultimately presentation of the conditioned
stimulus alone will evoke the response that
originally could elicited only by the unconditioned
stimulus.
§ Extinction: If the conditioned stimulation is
presented repeatedly without the unconditioned
stimulation, the conditioned reflex eventually dies
out.
Mechanism of memory§ Morphology
l Association areas of cortex, hippocampus, thalamus
l New synaptic connections established
§ Neurophysiology
l Duration of neuronal activities
l Neuronal circuits (Papez circuit)
l Synaptic activity (habituation, long-term potentiation)
§ Biochemistry
l Protein synthesis
l Neurotransmitters (ACh, catecholamine,
vasopressin)
Structures Involved in Declarative Memory
§ Declarative memory involves the following
brain areas:
l Hippocampus and the amygdala
l Specific areas of
the thalamus and
hypothalamus
l Ventromedial
prefrontal cortex
and the basal
forebrain
Major Structures Involved with Skill Memory
§ Skills memory involves:
l Corpus striatum – mediates the automatic connections between a stimulus and a motor response
l Portion of the brain receiving the stimulus (visual in this figure)
l Premotor and motor cortex
Synaptic plasticity
§ Habituation
§ sensitization
§ Long-term potentiation (discovered in year 1973)
Sensitization
§ A repeated stimulus produces a greater
response if it is coupled one or more
times with an unpleasant or a pleasant
stimulus, e.g. the mother who sleeps
through many kinds of noise but wakes
promptly when her baby cries.
What is long-term potentiation (LTP)?
§ LTP is an electrophysiological
measure of sustained increase
in synaptic efficacy when given
high-frequency stimulation
§ Cellular and behavioral studies
suggest that learning and
memory can be modeled by
LTP
Time (min)
-20 0 20 40 60 80 100 120 140 160 180
fEP
SP
slo
pe (
% c
han
ge o
f b
aselin
e)
0
50
100
150
200
250
300
Field EPSPs
High-frequency stimulation
Alzheimer’s Disease & Senile Dementia
§ Alzheimer’s disease is defined as premature aging of the
brain, usually beginning in mid-adult life and progressing
rapidly to extreme loss of mental powers—similar to that
seen in very, very old age.
§ AD is associated with accumulation of brain Beta-Amyloid
Peptide. The peptide accumulates in amyloid plaques found
in widespread areas of the brain. Thus, AD appears to be a
metabolic degenerative disease.
§ Vascular Disorders May Contribute to Progression of AD.
CEREBRAL DOMINANCE
AND LANGUAGE
Cerebral dominance§ The function of the speech and its control areas
are usually much more highly developed in one
cerebral hemisphere than in the other. This is
called the dominant hemisphere.
l concerned with sequential-analytic process
(categorical hemisphere)
l Its lesion: language disorders.
§ The other hemisphere: identification of objects
by form, recognition of musical theme
(representational hemisphere). Its damage
produces agnosia.
§ Related to handedness
Left and Right Hemisphere
§ The left hemisphere usually is the
dominant one. It excels in mathematical
ability, symbolic thinking, sequential
logic. The areas in temporal lobe
concerned with language ability.
§ Large number of artists, musicians are
left-handers.
Left and Right Hemisphere
Left-hemisphere:
§ Sequential analysis
l Analytical
l Problem solving
§ Language
Right-hemisphere:
§ Simultaneous analysisl Synthetic
§ Visual-Spatial skillsl Cognitive maps
l Personal space
l Facial recognition
l Drawing
§ Emotional functionsl Recognizing emotions
l Expressing emotions
§ Music
corpuscallosum
Unable to name the object in the left part of visual field
Able to identify the object and image
Split-brain
Epileptic activity spread
from one hemisphere
to the other through
corpus callosum
Since 1930, such epileptic
treated by severing the
interhemispheric
pathways
Verbal report ?
categorical
hemisphere
Handedness
§ In right-handed, 96% the left- dominant ,
remaining 4% the right-dominant.
§ In left-handed, 15% the right-dominant, 15%
not clear, 70% the left-dominant.
§ Dyslexia (impaired ability to learn and read,
12 times as common in left-handers as they
are in right-handers.
Physiology of Language§ Language is one of the fundamental
bases of human intelligence, a key part of
human culture.
§ Wernicke’s area is concerned with
comprehension of auditory/visual
information. Responsible for recognition &
construction of words.
Language areas
§ Located in a large area surrounding the left
(or language-dominant) lateral sulcus
§ Major parts
l Wernicke’s area
l Broca’s area
l Angular gyrus
• behind the Wernicke’s area
• processes information from words that are read
In 1908, Dr. Brodmann
numbered areas of cortex
according to cortical cell
arrangement. These
correspond with human
functions.
Areas 44, 45 (Broca’s
area) – Expressive speech
areas
Areas 41, 42 – Primary
auditory
Area 22 (Wernicke’s) –
receptive speech, auditory
perception comprehension
Wernicke’s Area (Brodmann’s 22)
§ in superior temporal gyrus, near auditory cortex
§ comprehension of auditory and visual information
(Receptive speech -- language comprehension)
§ projects to Broca’s area (via arcuate fasciculus)
§ Wernicke’s aphasia
l Fluent
l Syntactical but empty sentences, often make no sense
(contains many paraphasias)
l Used to be thought to be crazy
l Unable to understand what they read
or hear
Broca’s Area (Brodmann’s 44 & 45)
§ in frontal lobe, in front of the inferior motor
cortex
§ processes information into coordinated pattern
(Expressive speech)
§ projects the pattern to motor cortex
(vocalization)
§ Broca’s aphasia
l Nonfluent, labored, and hesitant speech
l Comprehension relatively intact (can understand)
Path taken by impulses when a subject names avisual object, projected on a horizontal section
PET scans of the left cerebral hemisphere
Nonhuman Primates
§ Vocalizations look preprogramed,
serving specific purposes only
§ Initiated by sub-cortical areas like limbic
system
§ But for vocalization and decoding, they
also use left hemisphere
Language Disorders
§ Egyptians reported
speech loss after blow
to head 3000 years ago
§ Broca (1861) finds
damage to left inferior
frontal region (Broca’s
area) of a language
impaired patient, in
postmortem analysis
Broca’s area
Wernicke’s area ( posterior end of the
superior temporal gyrus)
Angular gyrus
(area 39)
posterior part of intermediate frontal gyrus
W
S
H
V
S: motor aphasia
W: agraphia
H: sensory aphasia
V: alexia
Language disorders caused by lesions in the categorical hemisphere
Language Disorders
§ Nonfluent aphasia (Borca’s aphasia):
l Talking with considerable effort (Nonfluent speech)
§ Fluent aphasia
l Wernicke’s aphasia (Fluent speech but
unintelligible)
l Conduction aphasia (auditory cortex)
§ Anomic aphasia:
l Angular gyrus damage
§ Dyslexia
Dyslexia
§ Problem in learning to read
§ Common in boys and left-handed
§ High IQ, so related with language only
§ Postmortem observation revealed anomalies in the arrangement of cortical cellsl Micropolygyria: excessive cortical folding
l Ectopias: nests of extra cells in unusual location
§ Might have occurred in mid-gestation, during cell migration period
SUMMARY-terms
§ autonomic nervous system
§ vital centers
§ Circadian rhythms
§ Instinctual behavior
§ Evoked cortical potential
§ alpha block
§ Conditioned Reflex
§ dominant hemisphere
SUMMARY-questions
§ Function of ANS on the target organs
§ Hypothalamus regulation of visceral
function
§ Name two types of sleep, describe their
characteristics and the distribution of
sleep stages.