LECTURE 1 Reading Assignment: Chapter 1 and the Preface in Kolb

1
LECTURE 1Reading Assignment Chapter 1 and the
Preface in Kolb Whishaw
2
Lecture 1. Introduction to the Study of the
Nervous System
Here are some things you should learn from this
first lecture. 1. Understand how brain function
and structure is related to natural
selection. 2. Understand the concept of
localization of function and appreciate its
history. 3. Recognize pioneers in the field of
neuroscience. 4. Explain what factors determine
the overall structure of your brain. 5.
Understand the mechanist-vitalist controversy and
how it relates to brain behavior. 6. What
limitations do human brains have?
3
I. What is the Function of the Nervous System?

• A. Internal Communication and Homeostasis
• B. Monitoring of and Response to External
  Environment

4
II. Levels of Study of the Nervous System

• A. Molecular/Biochemical
• B. Cellular
• C. Cell Assemblies and Circuits
• D. Organ System
• E. Behavioral

5
III. Determinants of Nervous System Structure

• A. Evolution and Natural Selection
• B. Gene Action and Development

6
IV. History of Neuroscience - How Did We Get
Here?

• A. The Mechanist-Vitalist Controversy
  (Aristotle, Decartes and Darwin)
• B. Cell Pioneers Organ System Pioneers
• C. The Struggle over Localization of Function
• 1. Memory Storage - Karl Lashley
• 2. Phrenology - Franz Gall
• 3. Broca - "Nous parlon avec l'hemisphere
  gauche"
• 4. Wernicke - Connectionism
• 5. Wilder Penfield - Brain Stimulation
• D. The Emergence of Circuits as a Concept

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V. Adaptation and the Human Brain

• A. Why the First Two Years of Medical School
  are a Bitch
• B. Limitations on the Human Brain
  Implications for Medicine and for Physicians
• C. Learning and Memory Lessons for Medical
  Students from Brain Research

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Lecture 2. Principles of Nervous System Function

• What Do I Want You to Learn from this Lecture?
• 1. What two major ways the nervous system uses
  to transmit information?
• 2. Know what is ment by localized and
  distributed processing.
• 3. Know some general characteristics of CNS
  circuits?
• 4. Understand the concept of up or down
  regulation of receptors.
• 5. Know what is ment by hierarchial and
  parallel organization.
• 6. Understand how reflexes are classified.
• 7. Understand the characteristic features of
  reflexes.
• 8. Understand what neurorophic factors are and
  why they are important?

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LECTURE 2Reading Assignment Chapter 2 in
Kolb Whishaw.
10
I. Structure versus Function in Neuroscience

• The first part of Chapter 2 in the text outlines
  basic anatomical relationships in the CNS. Your
  neuroanatomy lectures will provide insights
  about CNS structures and how they are connected
  to each other, but in order to grasp how these
  structures produce behavior, certain operating
  principles must first be considered. Some of
  hese principles are disucssed in the last part of
  Chap. 2.
• A. In - Integrate - Out
• B. Sensory and Motor Components
• C. Crossed Inputs and Outputs
• D. Symmetrical and Asymmetrical Components
• E. Excitation and Inhibition
• F. Hierarchial Organization
• G. Parallel Organization
• H. Localized and Distributed Processing

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II. Signaling in the CNS - General Principles

• Communication within the nervous system occurs by
  two principle methods by the release and
  reception of chemical signals and by the
  production and propagation of nerve impulses. It
  is important to appreciate that both modes of
  information transfer occur simultaneously within
  the nervous system. Neurons are specialized to
  send information over long distances using ionic
  currents cascading down the cell membrane to
  generate digital signals. This type of
  communication is more rapid than transmitting
  chemical messages in the blood. However, not all
  important elements of CNS function results from
  electrical impulses in neuron circuits. Much of
  the brain's work is done the old fashioned way by
  the use of chemical signals borne in the blood or
  in the interstitial and cerebrospinal fluid. In
  this respect the brain is like most other organs.
  If the student really wishes to understand how
  the brain works, a thorough knowledge of CELL
  BIOLOGY is essential.

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II. Signaling in the CNS - General Principles

• A. Chemical messages from neurons released at a
  synapse are called neurotransmitters.
  Non-synaptic chemical messages originating from
  neurons, from glia or from other cell types
  within and outside the brain are also important.
• 1. There are many types of neurotransmitters.
• a. Amino Acids and Amino Acid Derivatives
• b. Polypeptides
• c. Acetylcholine
• d. Gases

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II. Signaling in the CNS - General Principles

• 2. Neurotransmitters act by binding to receptors
  on the target cell (postsynaptic receptor) or on
  the cell that released them (autoreceptor). A
  neurotransmitter or any substance that may
  potentially bind to a receptor is referred to as
  a ligand.
• 3. Non-neurotransmitter chemical signals acting
  on the brain can be classified into two basic
  groups
• a. Signals acting on intracellular receptors.
• i. steroids
• ii. thyroid hormone
• b. Signals acting on membrane receptors.
• i. proteins
• ii. amino acid derivatives, e.g.,
  serotonin, adrenaline, etc.

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II. Signaling in the CNS - General Principles

• 4. Neurotropins are an example of
  non-neurotransmitters important in neuron
  function.

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II. Signaling in the CNS - General Principles

• B. Receptors are large proteins often with
  several subunits.
• There are two types - intracellular and membrane
  bound.
• The number of receptors produced by a cell can be
  regulated to compensate for chronically low or
  high ligand concentrations.
• A receptor may bind different substances on
  different domains of the molecule.

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III. Circuits in the CNS - General Principles

• By connecting cells into specific circuits
  information can be transmitted in a highly
  specific fashion. A knowledge of particular
  circuits can be useful in diagnosing pathology in
  the nervous system.
• A. Circuits transmit information through action
  potentials, i.e., nerve impulses.
• B. Several simple circuits may be hooked up to
  form more complex circuits.
• C. Most circuits are produced from genetic
  instructions during embryonic and fetal
  development.

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III. Circuits in the CNS - General Principles

• D. Unused circuits are often dismantled unless
  maintained by activity dependent processes, e.g.,
  neurotrophic factors.
• E. Reflexes consist of simple circuits and are
  the elementary units of function of the nervous
  system. They involve a sensory neuron, a motor
  neuron and often one or more interneurons.
  Generally speaking, the more interneurons
  involved, the less "reflexive" a reflex is.
  Reflexes, like other more sophisticated behavior
  programs such as fixed action patterns, are
  indicators of the underlying neural function.
  Abnormal reflexes indicate pathology along the
  circuit. The location of the neurons in the
  circuits of many reflexes are known and the
  clinician can test for pathology in many brain
  regions by artifically eliciting reflexes.

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IV. Reflexes are classified in different ways by
different  authors, depending on one's point of
reference.

• A. Somatic versus Autonomic Reflexes
• 1. Somatic reflexes consist of circuits
  that involve skeletal muscles, whereas autonomic
  reflexes rarely involve skeletal muscle
  endpoints.
• 2. Visceral reflexes commonly involve fibers
  from both the autonomic nervous system and the
  somatic nervous system, and therefore, such
  reflexes are ususally under some degree of
  conscious control and can, within limits, be
  conditioned. It is important to recognize that
  some neural control mechanisms contain primarily
  autonomic efferent fibers, others contain
  primarily somatic efferents and some contain both.

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IV. Reflexes are classified in different ways by
different  authors, depending on one's point of
reference

• B. Superficial versus Deep Reflexes
• 1. Superficial reflexes are elicited by
  stimulation of mucous membranes or skin
• -examples include corneal, snout,
  rooting,suckling, abdominal, plantar,
  cremasteric, and sphincter
• 2. Deep Reflexes are stretch reflexes

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IV. Reflexes are classified in different ways by
different  authors, depending on one's point of
reference

• C. Normal versus Pathological Reflexes
• 1. During development cerebral cortex begins to
  exert inhibition on various circuits in the brain
  stem and cord resulting in the disappearance of
  reflexes in these areas.
• 2. In adulthood, infantile reflexes may reoccur
  as pathological signs, e.g. Babinski's reflex,
  indicating that damage exists to the cortical
  control mechanism

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IV. Reflexes are classified in different ways by
different  authors, depending on one's point of
reference

• D. Classification according to connections in
  cord and brain stem
• 1. Segmental reflex such as stretch reflex
• 2. Intersegmental such as flexion withdrawal
• 3. Suprasegmental such as swallowing

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V. Characteristic Features of Reflexes

• A. Reflexes, like more complex functions of the
  nervous system, have parallel and hierarchial
  organization. A hierarchy of reflexes controls
  which reflex will occur when two reflex pathways
  are stimulated simultaneously.
• B. Reflexes are graded responses that reflect
  the intensity of the stimulus.
• C. Reflexes are characterized by a fixed spatial
  relationship between the site of stimulation and
  the particular muscles that contract this
  relationship is called the local sign.
• D. Unlearned reflexive responses to complex
  environmental stimuli are more properly called
  fixed action patterns, e.g., smiling, grimaces,
  speech sounds, etc.

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LECTURE 3Reading Assignment Chap. 10 (pp.
356-365 386-387) in Kolb Whishaw
24
Lecture 3. Circuits in the Nervous System -
Somatic Reflexes

• What Do I Want You to Learn from this Lecture?
• 1. Understand the difference in circuitry
  between myotatic and inverse myotatic reflexes.
• 2. What is reciprocal and recurrent inhibition?
  
• 3. What is local sign and how does it apply to
  the flexion withdrawal reflex?
• 4. What is ment by saying that reflexes have
  somatic and autonomic components?
• 5. Discuss the interaction of the vomiting
  center in the medulla with other areas of the
  nervous system.
• 6. What sensory organs are involved in the
  myotatic and inverse myotatic reflex?
• 7. Understand how bladder function is
  controlled?
• 8. In what ways has an understanding of the
  physiology of vomiting contributed to
  therapeutic interventions?

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I. Somatic Reflexes are especially important for
osteopaths.

• A. The function of reflexes is not always
  apparent. Spinal reflexes are the first level of
  a hierarchy of motor response systems. This
  concept of hierarchial organization was first
  elaborated by the 19th century British
  neurologist, Hughling Jackson.

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I. Somatic Reflexes are especially important for
osteopaths

• B. The myotatic reflex probably operates to
  maintain muscle tone and occurs when the muscle
  is stretched.
• 1. studied by Charles Sherrington in late 19th
  century using cats and dogs
• 2. occurs in both flexor extensors but
  especially in anti-gravity muscles
• 3. muscle spindle 1a afferents excite homonymous
  muscle and synergists monosynaptically

27
I. Somatic Reflexes are especially important for
osteopaths

• 4. single 1a fiber may synapse on all alpha
  motor neurons innervating the muscle (300)
• 5. response may involve two types of inhibitory
  synaptic interactions
• -reciprocal inhibition through excitation of an
  interneuron connected to antagonist muscle
• -recurrent inhibition via a Renshaw cell that is
  excited by the alpha-motor neuron and in turn
  inhibits it this has the effect of dampening
  the intensity and duration of the reflex

28
I. Somatic Reflexes are especially important for
osteopaths

• C. Inverse myotatic reflex (clasp-knife reflex)
  occurs when 1b fibers from Golgi tendon organs
  are stimulated.
• 1. functions to dampen excessive tension by
  exciting antagonists and inhibiting
  homonymous muscle
• 2. action is via glycinergic interneurons
• 3. elicitation requires more tension than
  myotactic reflex
• 4. crossed extensor component

29
I. Somatic Reflexes are especially important for
osteopaths

• D. Flexor Withdrawal reflexes are mediated by
  skin receptors and pain receptors.
• 1. ipsilateral flexion and contralateral
  extension
• 2. functions to remove limb from potentially
  harmful stimulus and maintain balance
• 3. non-linear input-output relationship full
  blown response requires certain threshold hence,
  resembles fixed action patterns
• 4. light touch to foot pads may have opposite
  effect causing reflex extension (positive
  supporting reaction)
• 5. divergence occurs within the cord
• 6. final limb position is a function of site of
  stimulation (local sign)
• 7. withdrawal reflexes are prepotent, i.e., they
  preempt the spinal pathways from any other reflex
  activity taking place

30
I. Somatic Reflexes are especially important for
osteopaths

• E. Coughing, sneezing and gagging are reflex
  responses integrated in the medulla. Irritation
  of the nasal, tracheal, bronchial or esophageal
  mucosa induces activity in the glossopharyngeal
  and vagus nerves. Efferent fibers are mostly
  somatic.

31
II. Visceral Reflexes

• Visceral reflexes involve a neural response to
  sensory information coming from visceral organs.
  In some cases the responses involve both somatic
  and autonomic motor fibers resulting in some
  limited degree of conscious control over these
  reflexes.
• The reflex arc may be relatively restricted with
  local circuits in nearby ganglia playing an
  important role, or it may involve relatively
  localized spinal or supraspinal circuits termed
  "centers".

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II. Visceral Reflexes

• A. The neural mechanisms controlling micturition
  converge on a "center" in the sacral spinal cord.
• 1. Parasympathetic nerves in the micturition
  center in the sacral region send fibers via the
  pelvic nerves to synapse in pelvic plexus or in
  the intrinsic plexus of the bladder wall
  activation of the postganglionic fibers induces
  contraction of the muscles of the bladder wall.
• 2. Stimulation of sympathetic fibers in the
  lumbar cord causes contraction of the bladder
  neck.
• 3. Somatic fibers in the sacral cord control
  urethral contraction.
• 4. Sensory pathways from the bladder are not
  clearly understood, but most information on
  bladder filling is carried in the parasympathetic
  pelvic nerves.

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II. Visceral Reflexes

• B. Vomiting (Emesis) is coordinated by a center
  in the reticular formation of the medulla just
  beneath the 4th ventricle
• 1. Afferent fibers to vomiting center
• a. chemoreceptors in stomach intestine send
  signals via vagi and sympathetic nerves
• b. chemoreceptor trigger zone in area postrema
  sensitive to emetics
• c. input from retching area, higher centers and
  labyrinthae
• 2. Efferent fibers include both visceral
  somatic nerves.

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LECTURE 4Reading Assignment Chapter 2, Pp.
48-65 in Kolb Whishaw
35
Lecture 4. Circuits in the Nervous System -
Autonomic Reflexes

• What Do I Want You to Learn from this Lecture?
• 1. What areas of the CNS are involved in
  pupillary response to light and be able to
  explain how damage to one of these structures
  affects pupil size.
• 2. How is the swallowing process controlled by
  the nervous system?
• 3. Explain why sympathetic stimulation may cause
  muscle contraction in one tissue and muscle
  relaxation in another.
• 4. What factors induce the secretion of saliva?
• 5. What effect on the mouth would you expect to
  see after administering sympathomimetic drugs?
  What about the effect on swallowing?
• 6. How does the hypothalamus control body
  temperature? milk ejection?
• 7. How is fever produced and what is the role of
  interleukin-1 in fever production?
• 8. What is the basic circuitry for the medullary
  control of blood pressure?

36
I. Autonomic Reflexes

• There are autonomic components to the neural
  regulation of many body functions. In all cases
  the circuitry for these responses is complex,
  involves supraspinal circuits, and is
  incompletely understood.

37
I. Autonomic Reflexes

• A. Reflex control of the pupil diameter is
  consensual and is mediated by the innervation to
  the constrictor and dilator muscles of the iris.
• 1. Miosis is caused by stimulation of
  parasympathetic fibers
• 2. Mydriasis is caused by sympathetic
  stimulation
• 3. The pupillary reflex may be used to test
  for damage or pathology in the underlying
  neural circuits.

38
I. Autonomic Reflexes

• B. Swallowing (Deglutition) is a complex reflex
  with both autonomic and somatic components.
• 1. Afferent Fibers stimulated by pushing food
  to back of the mouth.
• a. Vagal, Glossopharyngeal
• b. Nucleus of the Tractus Solitarius/Nucleus
  Ambiguus
• 2. Efferent fibers are mostly vagal little
  sympathetic innervation.
• a. Parasympathetic fibers
• - preganglionic fibers synapse in myenteric
  plexus
• - anticholinergics block swallowing
• b. VIP and gastrin in lower esophageal
  sphincter
• - VIP may cause relaxation
• - high levels of gastrin cause
  constriction
• c. Lesions in the esophageal plexus may cause
  achalasia (excess tension in LES)

39
I. Autonomic Reflexes

• Salivation as an example of a process with
  autonomic controls. Parasympathetic stimulation
  induces profuse secretion of saliva low in
  organic material, whereas sympathetic stimulation
  induces secretion of small quantities of saliva
  rich in organics. Sympathetic stimulation
  affects the submandibular

40
I. Autonomic Reflexes

• Sympathetic stimulation affects the
  submandibular gland but not the parotid gland.
• 1. VIP induces local vasodilation
• 2. Atropine reduces salivation
• 3. Reflex secretion due to
• a. food in mouth
• b. stimulation of vagal afferents in lower
  esophagus

41
I. Autonomic Reflexes

• D. Other visceral and autonomic reflexes of
  considerable importance are those which control
  respiration, blood pressure, heart rate and
  digestion.
• 1. The NTS is a major integrating area of the
  medulla involved in the control of blood
  pressure.
• 2. The interomediolateral cell column of the
  cord is a final common path for signals involving
  sympathetic reflex control of heart rate and
  blood pressure.

42
II. Hypothalamic Reflexes - Body Temperature

• The hypothalamus is a major autonomic integrating
  center in the diencephalon, and many autonomic
  reflexes are seriously impaired when damage to
  the hypothalamus occurs. Body temperature
  regulation is controlled from the hypothalamus.

43
II. Hypothalamic Reflexes - Body Temperature

• A. Afferent fibers from cold receptors in the
  skin, spinal cord and viscera carry information
  to the hypothalamus.
• B. Receptors in the anterior hypothalamus are
  sensitive to local temperature changes.
• 1. Warm sensitive neurons increase their firing
  when the local temperature rises
• 2. Cold-sensitive neurons increase firing when
  local temperature drops.
• 3. Stimulation of anterior hypothalamus induces
  vasodilation in skin, panting blocks shivering.

44
II. Hypothalamic Reflexes - Body Temperature

• C. Posterior hypothalamic stimulation causes
  shivering, vasoconstriction in skin, etc.
  Efference includes both autonomic and somatic
  compontents.
• 1. Autonomic component - piloerection
• 2. Somatic efference - skeletal muscle
• D. Fever is produced by changes in the response
  threshold of the hypothalamic neurons.
• 1. Chill during fever produced due to activation
  of receptors monitoring peripheral
  vasoconstriction.
• 2. Interleukin 1 acts on hypothalamic receptors
  to induce changes in set-point possibly via
  release of prostaglandins.

45
III. Hypothalamic Neuroendocrine Reflexes - Milk
Ejection

• A. Sensory Input via tactile receptors in the
  nipple to the supraoptic nucleus and PVN.
• B. Posterior pituitary release of oxytocin
• C. Contraction of myoepithelial cells lining the
  ducts of breast.

46
LECTURE 5Reading Assignment Read about closed
head injury (see pg 2 of your text) and cerebral
palsy (see pg 248 of your text).Web Assignment
Visit www.braintrauma.org and learn more about
closed head injury.
47
Lecture 5. Physiology of CSF and the BBB

• What Do I Want You to Learn from this Lecture?
• 1. Describe and trace the formation, circulation
  and absorption of cerebrospinal fluid.
• 2. Describe the ontogeny of the ventricular
  system.
• 3. How does CSF differ from blood, from brain
  ISF?
• 4. What is the relationship between increased
  intracranial pressure and CSF flow?
• 5. What are the causes of hydrocephalus and
  brain edema?
• 6. What clinically useful information is
  available from analysis of the CSF?
• 7. Under what circumstances would the
  composition of CSF approach that of blood plasma?
• 8. How is intracranial pressure measured?

48
I. Introduction

• The cerebrospinal fluid (CSF) forms an
  environmental buffer and medium of communication
  for the brain. CSF is secreted by cells lining
  the walls of the ventricles and by the choroid
  plexus, a multitufted vascular organ located in
  the lateral, third and fourth ventricles. CSF
  fills the ventricles and cisternae and surrounds
  the brain thus providing a mechanical cushion in
  which the brain floats. It moves through the
  ventricles into the subarachnoid space, propelled
  by surges in blood volume and by the beating of
  cilia in the ventricles. CSF is separated from
  blood by the blood-brain barrier (BBB), and its
  composition differs in significant ways from the
  blood plasma. CSF is continuous with the
  extracellular fluid suggesting that substances
  introduced into the CSF may eventually diffuse
  deep into the interior of the cortex similarly
  substances secreted into the extracellular fluid
  by nerve cells will eventually end up in CSF.
  Because the CSF is a metabolic mirror of the
  brain, it is sometimes useful in diagnosis of
  neurological disease. This lecture will describe
  some of the properties of CSF which may be of
  interest to the physician.

49
II. Embryonic development of ventricular system
and CSF secretion.

• A. Ventricles of brain and central canal
  originate from the primitive neural tube of the
  embryo.
• 1. The neuraxis bends during development leaving
  various bulges and stenoses in the neural tube
  producing reservoirs and passageways for the CSF
  if a passageway becomes blocked at a narrow
  point such as at the Cerebral Aqueduct, pathology
  develops.
• 2. Choroid Plexus arises from mesodermal cells
  growing down into neural fold and joining
  ependymal cells from the inner layer of the
  neural tube

50
II. Embryonic development of ventricular system
and CSF secretion.

• B. C-shape of lateral ventricles and other brain
  structures, e.g., caudate nucleus, hippocampus
  results from early growth of the lateral cerebral
  hemispheres in a rostro-caudal direction.

51
III. Function of CSF

• A. CSF in the subarachnoid space acts to buoy
  the brain and protect it from striking the skull
  when the head moves.
• B. CSF serves as the route for the spread of
  neuroactive peptides and hormones and may serve
  as a reservoir of neuroactive substances that can
  be transported outward by glial tanycytes

52
IV. Composition of CSF

• A. Filtrate of Choroid Plexus - 90-150 ml total
  formed .35ml/min (500ml/day) Na is actively
  transported across the choroid epithelium.
• 1. Blood and CSF are in osmotic equilibrium
• 2. Active epithelial secretion of ions into CSF
  since digitalis glycosides inhibit the transport
  process
• 3. Sympathetic stimulation reduces CSF
  production
• B. Differences in chemical distribution
• 1. Elevated Mg and Cl-
• 2. Lower K, HCO3, Ca, glucose
• 3. Very little protein - accounts for clarity of
  fluid
• -albumin level of CSF is 0.5 of blood
• 4. Lumbar CSF is somewhat closer to blood in
  composition suggesting extra-choroid secretory
  elements

53
V. Pathophysiology of CSF

• A. The Monroe-Kellie doctrine states that an
  increase in the volume of any one of the
  compartments of the calvarium must be accompanied
  by a decrease in another compartment or
  intra-cranial pressure will rise.
• 1. Normal changes in brain blood volume are
  accompanied by surges in CSF movement from the
  ventricles into the subarachnoid space.
• 2. CSF pressure can be measured by lumbar
  puncture using a manometer and can be considered
  a guide to the pressure in the brain, however
  lumbar puncture when intracranial pressure is
  high may result in herniation of the cerebellum
  through the foramen magnum. (Normal 50-200 mm
  H20)
• 3. Increased intracranial pressure is usually
  accompanied by papilloedema, a swelling and
  elevation of the optic disk with blurring of the
  disk margin and by increased CSF pressure in the
  lumbar cistern.

54
V. Pathophysiology of CSF

• B. Brain edema (increased brain volume) and
  hydrocephalus (increased ventricular volume) may
  result from defects in CSF production, movement
  or removal, e.g., papillomas are tumors of
  choroid plexus which secrete excess CSF
• 1. Communicating hydrocephalus is due to
  impaired excretion of CSF through the
  subarachnoid villi.
• 2. Noncommunicating hydrocephalus results from
  stenosis of the cerebral aqueduct of Sylvius or
  blockage of the foramina of Luschka or the
  foramen of Magendie
• 3. Vasogenic edema results from an increase in
  brain capillary endothelial cell permeability
  causing an increase in extracellular fluid volume
• 4. Cytotoxic edema is increased intracellular
  volume due to failure of mechanisms removing Na
  from cells, e.g., inactivation of Na pump by
  hypoxia

55
V. Pathophysiology of CSF

• C. Normally CSF contains very few blood cells,
  so more than 5 cells per cubic mm suggests the
  presence of disease in the brain or meninges.
• D. The protein content of the CSF is normally
  low and analysis by electrophoresis of the
  immunoglobulin fraction may help in diagnosis of
  certain diseases.
• 1. Oligoclonal bands of Ig G and multiple
  sclerosis
• 2. Myelin basic protein (MBP) and demyelinating
  disease MBP is limited to the CNS injection of
  MBP produces experimental allergic
  encephalomyelitis

56
VI. The blood-brain barrier (BBB) controls what
enters the CSF and what enters the extracellular
fluid of the brain.

• A. Tight junctions in the endothelial cells of
  the cerebral capillaries and in the epithelium of
  the choroid plexus produce the BBB.
• B. The circumventricular organs of the brain lie
  outside the BBB.
• C. Some substances pass more readily through the
  BBB than others.
• 1. Molecular size is inversely proportional to
  rat of passage, and large proteins hardly pass
  the BBB.
• 2. Lipid soluble substances pass more readily
  than polar compounds

57
VI. The blood-brain barrier (BBB) controls what
enters the CSF and what enters the extracellular
fluid of the brain.

• D. The capillary endothelial cells act as
  metabolic regulators of what enters and exits the
  CNS.
• E. The BBB may be disturbed in various disease
  states.
• 1. Tumors in the brain frequently have faulty
  BBB,s and this property may be helpful in
  localizing the tumor.
• 2. Some brain diseases, such as meningitis alter
  the BBB such that substances normally excluded
  may be used therapeutically, e.g., penicillin.
• F. Brief periods of hyperosmolarity can "unzip"
  the tight junctions of the BBB and may be used to
  advantage in treating some brain infections.

58
LECTURE 6Reading Assignment Read part of Chap.
4 (pp.138-139) and Chap 8 (pp. 279-280) in Kolb
Whishaw
59
Lecture 6. Principles of Sensory Transduction

• What Do I Want You to Learn from this Lecture?
• 1. Be able to categorize all sensory systems.
• 2. What is the relationship between the receptor
  and the adequate stimulus?
• 3. How are stimuli encoded by sensory systems?
• 4. What is a receptive field?
• 5. How does convergence and divergence of
  neuronal connections influence information
  processing?
• 6. Know how redundancy is built into sensory
  systems and why it is important.
• 7. Describe the relationship between magnitude
  of the sensory stimulus and frequency of action
  potentials in the afferent nerve.
• 8. Know how the receptive field of a sensory
  receptor cell differs from the receptive field of
  a sensory neuron located in the spinal cord,
  thalamus or cortex..

60
I. Classification of Sensory Systems

• A. Sherrington's Classification is still in use.
• 1. Proprioceptors provide information about the
  relative position of the body segments and their
  position in space.
• 2. Exteroceptors are sensitive to external
  stimuli and include taste, touch, pressure, pain
  and may also include vision, audition and smell.
• 3. Interoceptors monitor internal bodily events.
• 4. Teleceptors are concerned with detecting
  distant external events, and include vision and
  audition.

61
I. Classification of Sensory Systems

• B. Clinical Classification
• 1. Special Senses are served by cranial nerves
  and include smell, taste, rotational linear
  acceleration, vision and audition.
• 2. Superficial or cutaneous senses are those
  with receptors in the skin.
• 3. Deep Sensations are position senses in the
  muscles and joints.
• 4. Visceral Sensations are those concerned with
  perception of the internal environment.
• C. Other classifications include functional and
  descriptive terms such as audition, olfaction,
  mechanoreceptors, etc.

62
II. Sensory Receptors and the "Adequate
Stimulus"

• A. Secondary and Primary Receptors differ in
  terms of the embryological origin of the receptor
  cells.
• 1. Receptors produce a receptor potential or
  generator potential.
• 2. Secondary receptors are of non-nervous
  origin, e.g., hair cells in taste receptors, and
  they communicate with the primary afferent
  neuron.
• B. Receptors are specialized for detecting
  specific kinds of energy and transducing it into
  electrochemical energy.

63
II. Sensory Receptors and the "Adequate
Stimulus"

• C. What Qualities of Stimuli do receptors
  respond to or what features are extracted?
• 1. Qualitative
• 2. Quantitative
• 3. Temporal
• 4. Spatial
• D. Evolutionary refinement of receptor structure
  has reached a theoretical limit for some receptor
  types.

64
III. Stimulus Encoding occurs in two basic ways.

• A. Place Coding
• B. Frequency Coding

65
IV. Adaptation and Habituation may contribute to
discrimination of stimulus change.

• A. Fast Adapting or phasic receptors
• B. Slow Adapting or tonic receptors
• C. Habituation is mediated centrally.

66
V. Sensation and Perception

• A. Sensory Filtering occurs at every level of
  analysis.
• B. Sensory Threshold - What are the Limits?
• C. Weber-Fechner Law relates the strength of the
  stimulus to the individual's perception of its
  strength.
• D. Stevens Law is a refinement of the
  Weber-Fechner Law.
• E. Sensation is related to ecological niche
• 1. Function of Sensation
• 2. Is Pain always Painful?

67
VI. Properties of Sensory Fibers

• A. Classification of Fiber Size
• B. Fiber Pathways
• 1. Convergence occurs when many diverse cells
  send projections to one or a few afferent
  neurons this is necessary for feature
  extraction.
• 2. Divergence occurs when a single afferent cell
  projects to multiple cells also permits feature
  abstraction.
• C. Sensory Fibers have Receptive Fields
• D. Redundancy is important in information
  processing
• 1. New information is abstracted at each level
  of processing.
• 2. Information is processed simultaneously in
  different circuits (parallel processing).

68
LECTURE 7Reading Assignment Chapter 10
(pp.380-397)in Kolb Whishaw Read about
Synesthesia on Page 564 of your text.
69
Lecture 7. Tactile and Position Senses

• What Do I Want You to Learn from this Lecture?
• 1. Discuss the receptors, pathways and
  terminations for crude touch and for fine touch.
• 2. How are fast adapting and slow adapting
  fibers important for tactile sensation?
• 3. What classes of fibers conduct tactile
  information?
• 4. How is the sensory input organized in the
  thalamus and cortex?
• 5. What techniques are available for measuring
  tactile sensation?
• 6. How does the activity of the muscle spindle
  allow the organism finer control over muscle
  contraction?
• 7. How does the information about body position
  reach the brain?
• 8. Distinguish the dynamic from the static
  response of the muscle spindle.

70
I. Introduction

• In order to control the muscle contraction
  patterns which produce movement of the body,
  information on the position of the various body
  parts in space is essential. This information is
  gained by several different receptor systems
  located in the muscles, joints, tendons, and in
  the inner ear. The information forms the basis
  for numerous reflexes and for the organization of
  motor output to the skeletal muscles. Most of
  this information is not processed at a conscious
  level, but the sense of knowing, where in space,
  your arms and legs are, is termed kinesthesia.

71
I. Introduction

• Tactile sensations arise from stimulation of
  receptors in the skin. There are both primary
  and secondary receptors in the skin which convey
  information about mechanical distortion of the
  skin surface. Sensations arising from
  stimulation of these receptors are frequently
  divided into discriminative touch, deep touch or
  pressure, vibration sense and crude touch. Crude
  touch is phylogenetically older and less
  topographically organized. Sometimes other
  cutaneous sensations such as pain and temperature
  and proprioception are grouped with these senses
  under the umbrella term, somasthesia.

72
II. There are three basic classes of peripheral
receptors which provide information needed for
control of muscle contraction.

• A. Joint proprioceptors signal joint angle and
  angle change.
• 1. structure
• 2. fiber size
• 3. response patterns

73
II. There are three basic classes of peripheral
receptors which provide information needed for
control of muscle contraction.

• B. Muscle Spindles consist of 2 - 10 muscle
  fibers (intrafusal fibers) surrounded by sensory
  nerve endings and enclosed by a connective tissue
  capsule. They are capable of dynamic and static
  responses to muscle action.
• 1. There are two basic kinds of sensory endings
  in a muscle spindle. Primary or Annulospiral
  Endings are on Bag Fibers and Chain Fibers,
  whereas Secondary or Flower-spray Endings are on
  Chain Fibers.
• a. termination site
• b. fiber size
• c. response properties
• 2. The reponse range of the muscle spindle is
  increased by a Gamma Efferent Motor Neuron.

74
II. There are three basic classes of peripheral
receptors which provide information needed for
control of muscle contraction.

• C. Golgi Tendon Organs signal stretch on the
  tendon.
• 1. structure
• 2. fiber size
• 3. response properties

75
III. There are several types of tactile
receptors, and each type responds more easily to
some kinds of stimuli than other kinds (adequate
stimulus).

• A. Glabrous skin and Hairy skin have different
  receptor distributions. Meissner Corpuscles are
  not found in Hairy skin and hair receptors are
  absent from glabrous skin. Hyperemia influences
  the quality of sensation, e.g., male genitalia.

76
III. There are several types of tactile
receptors, and each type responds more easily to
some kinds of stimuli than other kinds (adequate
stimulus).

• B. Receptors are either slow adapting or fast
  adapting
• 1. Slow adapting receptors - related to pressure
  sensation
• a. Merkels Discs (Iggo dome receptor) found in
  the superficial portion of the dermis contains a
  synapse.
• b. Ruffini's end organs found deeper and have
  larger receptive fields
• 2. Fast Adapting receptors - related to light
  touch.
• a. Meissner Corpuscle found in superficial
  dermal papillae
• b. Pacinian Corpuscle found in the subcutaneous
  tissue.

77
III. There are several types of tactile
receptors, and each type responds more easily to
some kinds of stimuli than other kinds (adequate
stimulus).

• C. Some parts of the skin are more sensitive
  than others. Minimum stimulus intensity varies,
  with the nose,lips and tips of fingers being most
  sensitive (2g/mm2) and the loin the least (50
  g/mm2). This correlates with receptor densities
  in the various areas. Energy required for
  generating a sensation is 108 more than with
  hearing.
• D. Tactile sensory information is carried mostly
  in large myelinated A-beta fibers, but crude
  touch may use smaller fibers.
• E. Dermatomes mark areas of spinal nerve
  innervation of skin surface.

78
IV. Spinal Afferent Fiber Organization - Two
Basic Routes to the Brain. Sensory fibers with
cell bodies in dorsal root ganglion enter the
cord and ascend in parallel systems to the
brain.

• A. Crude touch is mediated mainly by the
  Anterolateral System, sometimes called the
  spinothalamic system. Fibers synapse on dorsal
  horn cells at or near level of entry into cord
  and second order neurons then cross over and
  ascend in the spinothalamic tract. Closely
  related to pain sense.
• 1. Generally small unmyelinated fibers.
• 2. Transmission rate is slow
• 3. Pathway also transmits pain, thermal, tickle,
  itch and sexual sensations.
• 4. Low degree of spatial orientation.
• 5. Axons may terminate in reticular formation,
  midbrain tectal area or thalamus.

79
IV. Spinal Afferent Fiber Organization - Two
Basic Routes to the Brain. Sensory fibers with
cell bodies in dorsal root ganglion enter the
cord and ascend in parallel systems to the brain.

• B. Dorsal Column (Medial Lemniscal) System,
  sometimes called Posterior Columns, mediates
  mostly discriminative touch, pressure and
  vibration. It also carries proprioceptive inputs
  from the arm. The fibers first synapse in the
  dorsal column nuclei in the medulla.
• 1. Large myelinated fibers ascend ipsilaterally.
• 2. Fasiculus gracilis and fasiculus cuneatus end
  in the corresponding nuclei in medulla.
• 3. Distinct spatial fiber orientation
• a. fibers from lower parts of body lie toward
  center and upper parts more more lateral
• b. orientation changes at different levels

80
IV. Spinal Afferent Fiber Organization - Two
Basic Routes to the Brain. Sensory fibers with
cell bodies in dorsal root ganglion enter the
cord and ascend in parallel systems to the brain.

• 4. Second order fibers course ventrally through
  the medulla asinternal arcuate fibers and ascend
  medially to thalamus as the Medial Lemniscus.
• 5. Transmits fine gradations of intensty.
• 6. Vibration sense due to ability of dorsal
  columns to transmit rapid volleys neurologists
  use tuning fork to test this tract, but some
  vibration sensory information is carried in the
  lateral funiculus.

81
IV. Spinal Afferent Fiber Organization - Two
Basic Routes to the Brain. Sensory fibers with
cell bodies in dorsal root ganglion enter the
cord and ascend in parallel systems to the brain.

• C. Kinesthetic information from the legs are
  carried in a separate pathway (Spinocerebellar
  Tract) which merges with other dorsal column
  afferents at the level of the brain stem.

82
V. Cranial Nerve Afferents for tactile senses
are carried mostly in the trigeminal nerve.

• A. Main sensory nucleus of trigeminal nerve in
  pons receives information analagous to that
  carried in dorsal columns.
• B. Nucleus of the Spinal tract of trigeminal
  receives information analagous to that carried in
  anterolateral system.

83
VI. Thalamic and cortical organization is
topographical

• A. Several thalamic cell groups receive tactile
  input.
• 1. Discriminative touch relays are in the
  ventral posterior nucleus (VPN).
• 2. Crude touch relays are in the VPN, posterior
  nuclear group and the intralaminar nucleus.
• B. The body surface is represented in at least
  four separate cortical areas in macaques and
  presumably also humans.
• 1. SI contains areas 1,2,3a and 3b which are
  functionally distinct.
• 2. SII is located adjacent to SI on the upper
  bank of the lateral fissure.

84
VII. Lesions of the somatosensory cortex may
produce very specific tactile agnosias.

• A. Lesions of SI cause loss of position sense
  for limbs and difficulties in identifying or
  discriminating higher order properties of tactile
  stimuli.
• 1. Astereognosis is inability to recognize
  objects by touch.
• 2. unable to identify a number or letter traced
  on skin
• 3. unable to judge exactly weights (abarognosia)
• 4. unable to judge textures
• B. Measuring tactile deficits
• 1. Two-point discrimination
• 2. Topagnosia - inability to localize source of
  touch

85
LECTURE 8Assignment Read Science Article by
M. Lotz et al and answer questions in problem set.
86
Lecture 8. Pain and Temperature

• What Do I Want You to Learn from this Lecture?
• 1. Distinguish the pattern hypothesis from the
  specificity theory of nocioceptive transmission.
• 2. What do pain receptors look like and how is
  information on pain carried to the brain?
• 3. What are some possible mechanisms through
  which abnormal activity in pain fibers can lead
  to pathology?
• 4. How do cutaneous and visceral receptive
  fields for pain fibers differ?
• 5. What physiological processes generate
  analgesia.
• 6. How is nocioceptive input regulated
  centrally?
• 7. Understand the potential mechanisms of
  referred pain.
• 8. What are the chemical signals and mediators
  of pain, and what is the Gate Control Theory of
  Pain?
• 9. How are the mechanisms for sensing
  temperature different from those sensing pain?

87
I. Introduction

• Pain and temperature are intimately related in
  their reception and transmission. There is some
  overlap in the response of fibers which transmit
  information about tissue damage and fibers which
  transmit information about changes in
  temperature. The pattern hypothesis of pain
  argues that the receptors and transmission lines
  to the CNS are shared among different sensory
  modalities and that only the pattern of
  stimulation is interpreted as pain or temperature
  or touch. Specificity theory argues that
  specific transducers exist for pain and that the
  perception of pain is a result of activation of
  these labeled lines. Currently available
  evidence supports the specificity theory more.
  Nocioception is the term applied to stimulation
  that can lead to tissue damage if this
  stimulation is felt or perceived as a negative
  affect, then it is termed pain. Because pain is
  a conscious interpretation of signals entering
  the CNS, there is a tremendous likelihood that
  the same signals will be interpreted differently
  depending on the time, place, conditions, etc.
  Hence pain may be intractable in lots of
  respects, e.g., scientifically, medically, etc.

88
II. Receptors and Afferent Fibers

• A. Receptors for Pain are free nerve endings.
• 1. A Generator Potential occurs in the free
  nerve ending due to various types of stimuli.
• a. mechanical - no response to low energy
  stimuli
• b. thermal
• c. chemical
• 2. Algogenic Substances induce pain.
• a. K released with tissue damage - K
  correlates with pain intensity
• b. prostaglandins sensitize all fibers types
  -asprin inhibits prostaglandin synthesis
• c. bradykinins and other plasmakinins
• d. ACh, 5-HT, histamine - present in venoms
• e. Interleukin-1

89
II. Receptors and Afferent Fibers

• 3. Distribution on skin and internal organs
• a. receptive field on skin 1.5 - 3 cm2 larger
  internally
• b. especially sensitive - skin of face, lips,
  coronea, muscous membranes of eyes, ears, nose,
  mouth throat parietal pleura, diaphram,
  coronary arteries
• c. digestive organs only sensitive if distended
• d. insensitive - pia mater, lungs, liver, spleen

90
II. Receptors and Afferent Fibers

• B. Receptors for Temperature are free nerve
  endings, Ruffini Endings, and Krauses End Bulbs.
• 1. Cold Sensitive Fibers
• 2. Heat Sensitive Fibers
• 3. Spatial summation may allow detection of
  changes as small as .01oC

91
II. Receptors and Afferent Fibers

• C. Cell bodies of the first order neurons are in
  DRG
• 1. Axons terminate in dorsal horn and in
  periphery where they may secrete transmitter
  which may induce local inflammation.
• 2. Visceral afferents may have collaterals
  ending in sympathetic or parasympathetic ganglia
  or in peripheral tissue near the receptor site.

92
II. Receptors and Afferent Fibers

• D. All pain fibers either do not adapt or adapt
  slowly (sharp pain) some temperature fibers are
  rapidly adapting.
• E. Different fiber systems mediate dull
  (protopathic) and sharp (epicritical) pain.
• 1. Delta-A Type fibers carry sharp pain
• a. myelinated
• b. adequate stimuli - strong pressure or heat
• c. easily localized
• d. called fast pain since fiber diameter larger
  (5-30m/sec)
• 2. C Type fibers carry dull burning pain
• a. non-myelinated and slower (.5-2m/sec)
• b. adequate stimulus probably chemical
• c. less easily localized
• d. longer latency and duration

93
III. Afferent Spinal Organization

• A. Primary somatic pain fiber enters and ascends
  or descends 1 - 3 segments in Tract of Lissauer
  before synapsing in dorsal horn
• 1. Termination sites in Lamina I or in Lamina II
  III (substantia gelatinosa).
• 2. Some delta-A types terminate in Lamina V

94
III. Afferent Spinal Organization

• B. Second Order Neuron is either a relay cell or
  interneuron.
• 1. Relay neurons from Lamina I make up
  neospinothalamic tract and project directly to
  thalamus
• 2. Relay neurons from deeper Laminae make up
  paleospinothalamic tract
• a. misnomer - most terminate in reticular
  formation of brainstem
• b. more medial fiber distribution
• c. medically most interesting
• 3. Most axons cross over to anterolateral
  quadrant - those that do not may be significant
  for understanding return of pain after cord
  section.
• 4. Terminal fields in ventrobasal complex of
  thalamus (neospinothalamic) and intralaminar
  nucleus (paleospinothalamic) large termination
  fields in tectum of midbrain and in periaquetal
  grey which have reciprocal connections with
  limbic system

95
III. Afferent Spinal Organization

• C. Visceral afferent pain fibers are carried in
  the same spinal tracts as cutaneous fibers.
• 1. Parietal visceral pain is more easily
  localized and is not carried through autonomic
  ganglia
• 2. Visceral pain may be associated with nausea,
  vomiting, pallor, sweating and may be caused by
  ischemia, spasms reflex contractions,
  overdistension, inflammation.
• D. Cranial Afferents are carried in Cranial
  Nerves V, VII, IX, X. Functional organization
  is as for touch.

96
IV. Thalamic and Cortical Organization

• A. Topographic organization retained in
  ventrobasal complex of thalamus
• B. Cortical projection is to SI and SII
  somatosensory area of parietal cortex.

97
V. The affective nature of pain is determined by
processing of nocioceptive input by higher brain
centers.

• A. Pain may be incorrectly localized (Referred
  Pain).
• 1. habit reference
• 2. dermatomal rule
• 3. convergence and facilitation theories

98
V. The affective nature of pain is determined by
processing of nocioceptive input by higher brain
centers.

• B. There are multiple neurochemical controls on
  pain sensation analgesia or hyperalgesia result
  from the action of various neurotransmitters on
  pain sensory neurons.
• 1. Opiate systems act in the spinal cord and at
  brain stem sites to block nocioceptive input.
• 2. There are descending inhibitory controls that
  are partly serotonergic.
• 3. Substance P is an important mediator of
  activity in spinal pain circuits.

99
V. The affective nature of pain is determined by
processing of nocioceptive input by higher brain
centers.

• C. Central inhibition of input from pain fibers
  may generate analgesia.
• 1. Stress-induced analgesia occurs frequently in
  man and animals.
• 2. The Gate Control Theory of Melzack Wall has
  led to techniques for pain treatment such as
  sub-cutaneous electrical stimulation (SCNS).
• 3. Hypnosis may induce analgesia, and it is not
  dependent on opiates since naloxone does not
  reverse it.
• 4. Some acupunture-induced analgesia is opiate
  dependent, especially that induced by distant
  needle placement.

100
V. The affective nature of pain is determined by
processing of nocioceptive input by higher brain
centers.

• D. Anesthesia is a generalized suppression of
  neural activity as opposed to analgesia which is
  the reduction of perceived pain.

101
VI. Unusual activity, especially hyperactivity,
in pain circuits may gradually cause disease.

• A. Stimulation of certain sensory neurons may
  induce antidromic liberation of substance P from
  the nerve endings of joints and the gradual
  development of arthritis.
• B. It is possible that the relief of pain
  induced by osteopathic manipulation is due to a
  redistribution of neural activity in afferent
  neural circuits similar to that induced by SCNS.

102
LECTURE 9 10Reading Assignment LA Times
article by T. Maugh on the work of Martha
McClintock
103
Lecture 9. The Gustatory SystemLecture 10. The
Olfactory System

• What Do I Want You to Learn from this Lecture?
• 1. How are the receptors for taste and smell
  similar and how are they different?
• 2. What are the primary stimuli that elicit
  activity in taste receptors?
• 3. Compare the central projections of taste and
  olfaction.
• 4. Damage to what neural structures are known to
  influence taste or smell?
• 5. How are odorant signals transduced and
  analyzed by the olfactory system?
• 6. What is the VMO and what is its significance
  in man?
• 7. How can smell be a factor in the
  physician-patient relationship.

104
I. Introduction

• Olfaction and taste are chemoreceptor sensations
  with similar modes of operation but different
  evolutionary histories. Olfaction is the
  phylogenetically oldest and, ironically, the
  least understood sensation. Both senses have
  multiple functions in most vertebrates including,
  food selection, habitat selection, social
  recognition and mating. Whether all these
  functions apply to man is an open question.

105
II. Taste

• A. Receptors are located in the oral cavity
• 1. Gustatory receptors are secondary receptors
  and are fouund in taste buds on the tongue,
  tonsils, pharnyx and larnyx
• -loss with age
• 2. Taste buds contain 3 types of epithelial
  cells and numerous neural processes.
• -hair cells - life span 10 days
• -basal cells - differentiate into support
  cells
• -support cells - differentiate into hair cell
• -primary afferent neurons
• 3. Taste buds are clumped together in papillae
• -fungiform
• -foliate
• -circumvallate
• 4. Taste buds deteriorate in absence of neural
  connection or axoplasmic flow
• -chemical synapses

106
II. Taste

• B. Three different nerves carry afferent taste
  information.
• 1. Chordi tympani, a branch of facial nerve
  (VII) carries fibers from anterior 2/3 of tongue
• -myelinated, cell body in geniculate ganglion,
  synapse in nucleus of solitary tract
• 2. Glossopharyngeal (IX) - posterior part of
  tongue
• -myleinated, cell body in petrosal ganglion,
  synapse in nucleus of solitary tract
• 3. Vagus (X) - all other gustatory inputs
• -myelinated, cell body in nodose ganglion,
  synapse in nuc. solitary tract

107
II. Taste

• C. Second order neurons in the solitary tract
  nucleus project to either motor neurons or other
  relay cells.
• 1. Rostral projections to VPM of thalamus via
  medial lemniscus with possible relay in
  parabrachial area. Projections are ipsilateral.
• 2. Rostral projections to salivary nuclei