2. Professor : James R. Moyer, Jr., Ph.D. Semester : Fall 2010 Office : Garland 208 Meeting Time : MW 9:00 – 9:50 a.m. Office hrs: MW 10:00 – 10:50 a.m. Meeting Place : ENG 105 Office ph: x3255 Psych Listing : 254–402 lecture Email: [email_address] Course Description This course is designed to provide each student with comprehensive exposure to the nervous system and how it governs various behaviors . The course will also cover relevant anatomical, behavioral, psychological, cellular, imaging, and neurophysiological approaches used to study animal behavior. Upon completion of the course, the student will have a solid foundation regarding the biological basis of behavior upon which to build in more advanced courses of study. Reading Materials The recommended textbook for this course is Carlson, NR (2010). Physiology of Behavior, 10 th Ed. Allyn & Bacon, New York, NY . (Note: there are a variety of texts on reserve in the library as well). Course Syllabus for Physiological Psychology

3. Determination of Your Final Grade Your overall grade will be determined by combining your scores from the following: 1. Discussion Section Attendance (10%) . Discussion sessions will begin Monday, September 13. TA will take attendance. If you cannot make your discussion session, you must make arrangements to attend one of the other 9 discussion sections that week . See page 6 of the syllabus for the weekly discussion session schedule . 2. Weekly Online Quizzes (25%) . There will be 12 open-book/notes quizzes available for you to take online beginning September 13 (each quiz will be available for one week). See page 7 of the syllabus for the quiz schedule. NO make-ups (if you fail to take a quiz you will receive a grade of zero for that quiz). 3. Regular Exams (40%). There will be 2 exams ( multiple-choice, true-false, matching questions ) scheduled during the semester (see dates on syllabus). Exams will be cumulative , which means that there will be some material from the previous exam(s) on each successive exam. 4. Final exam (25%). There will be a cumulative final exam on Tuesday, December 21, 2010 from 10:00 a.m. to 12:00 p.m. in ENG 105 . Any student who does not take the final exam will fail the course. The final grade for the course will be determined based on your final average according to the following scale: A = 93-100%; A- = 90-92%; B+ = 87-89%; B = 83-86%; B- = 80-82%; C+ = 77-79%; C = 73-76%; C- = 70-72%; D+ = 67-69%; D = 63-66%; D- = 60-62%; F = 0-59%. Course Syllabus for Physiological Psychology

4. Make-up, Curving and Extra Credit Make-up exam. Should a student fail to take one of the three scheduled exams during the semester, that student will receive a zero “0” as a grade for that exam. However, at the end of the semester a “one size fits all” cumulative make-up will be offered for students who missed one of the exams (no excuse or reason necessary). The make-up will be held on the study day at 9:00 a.m. on Wednesday, December 15 in ENG 105 . Curving of exams. I will not curve any of the exams. However, all exams will contain some extra credit questions. Thus, it is always possible to score greater than 100% on any exam, including the final. Extra credit. You may receive up to a maximum of 5 extra credit points, which will be added to your final exam score (thus, if you scored an 86% on the final and you did 5 points worth of extra credit, your final exam score would be a 91%). Check bulletin boards in Garland and Pearse for extra credit opportunities. I will also post some extra credit opportunities on the D2L, if an instructor requests an advertisement in class. Course Syllabus for Physiological Psychology

5. Getting Help If you are having difficulties or have questions, please do not hesitate to come in for a visit to discuss any issues pertinent to your academic success. If you are struggling in the class, don’t wait until you’ve taken numerous quizzes or both exams to come for help . One mistake students often make is waiting too long to come to me to discuss their performance in the class, which limits my ability to help the student. Course Syllabus for Physiological Psychology

7. History of Brain Research CARDIOCENTRIC explanations of behavior prevailed in ancient cultures • argued that the heart controlled thoughts, emotions and behavior • e.g., ancient Egyptians removed and discarded the brain before mummification but preserved the heart for the afterlife ENCEPHALOCENTRIC explanations of behavior emerged from dissections • argued that the brain controlled thoughts and emotions and behavior • Hippocrates (460-377 B.C.) after witnessing many dissections argued that the brain controls behavior • Plato (427-327 B.C.) agreed with Hippocrates • Aristotle (384-322 B.C.) disagreed & argued it “cools the heart” • Galen (130-200 A.D.) later concluded that Aristotle’s role for the brain was “utterly absurd” for two reasons: 1. The brain was too far away to cool the heart and 2. Too many sensory nerves were attached to the brain • René Descartes (1596-1650 A.D.) argued that the pineal gland is the seat of the soul and exerts its actions via pressure changes in the fluid-filled ventricles

8. Holism vs. Localization Controlled experiments involving the brain were quite rare until the 19th century. • Thus, two schools of thought emerged regarding the extent to which specific brain areas govern behaviors. Holism – argued that every area of the brain can control all human functions Localization – argued that human functions are regulated by distinct brain regions • Franz Gall (1757-1828) popularized localization based on his theories that specific brain protuberances (felt via skull) corresponded to specific personality traits “ Phrenology ” • Although not based on experimental evidence, Gall changed how many people thought about the brain and the work of future scientists supported localization of brain function.

9. 1861 – Paul Broca examined patient “Tan” who had a stroke ~20 yrs earlier.

10. 1876 – David Ferrier stimulated the motor cortex of monkeys and demonstrated that the indicated areas controlled movement of specific body parts: 1 and 2 hind limbs 3 tail 4, 5, 6 arm a, b, c, d hands and fingers 7-11 face and mouth 12, 13 eyes, head 14 ear 1870 – Fritsch and Hitzig stimulated the motor cortex of dogs and noted that stimulation near the top caused the hind legs to wiggle whereas stimulation near the bottom caused the jaw to move.

11. TOPOGRAPHICAL ORGANIZATION - Motor Cortex

12. TOPOGRAPHICAL ORGANIZATION - Motor Homunculus

13. TOPOGRAPHICAL ORGANIZATION - Somatosensory Cortex

14. TOPOGRAPHICAL ORGANIZATION - Somatosensory Cortex

17. PET scans reveal which specific brain regions are activated by a given task

18. PET scans reveal which specific brain regions are activated by a given task Sight Sound Touch Speech

19. PET scans reveal which specific brain regions are activated by a given task Sight Sound Touch Speech

20. PET scans reveal which specific brain regions are activated by a given task Sight Sound Touch Speech

21. PET scans reveal which specific brain regions are activated by a given task Sight Sound Touch Speech

22. WHERE’S THE MIND? Two schools of thought: Dualism – the mind and body (or brain) are separate. e.g., Plato “father of western dualism” e.g., René Descartes Monism – the mind is the result of brain functioning & follows physical laws e.g., Leonardo da Vinci (1452-1519) stated “mind is a product of the brain” e.g., most modern brain scientists

23. Physiological Approaches to Consciousness • Consciousness can be altered by changes in brain chemistry and thus we may hypothesize that it is a physiological function, just like behavior • Consciousness and ability to communicate seem to go hand in hand • Verbal communication allows us to send and receive messages from other people as well as send and receive our own messages (and thus think and be aware of our own existence)

25. An explanation of the blindsight phenomenon

26. MRIs of human brain showing corpus callosum (cc) corpus callosum

27. Identification of an object by smell in a split-brain patient

28. Identification of an object by sight in a split-brain patient

29. Angular Gyrus Activity and the Out of Body Experience

30. END – Lecture 01

31. ORGANIZATION OF THE NERVOUS SYSTEM • CNS vs. PNS THE CENTRAL NERVOUS SYSTEM I • Meninges, Ventricles, and Cerebrospinal Fluid • The Spinal Cord • Anatomical Coordinates PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 02 (September 13, 2010)

34. Ventricles & Flow of CSF • Lateral ventricle (2) • Third ventricle – aqueduct of Sylvius • Fourth ventricle – central canal

35. Flow of CSF (Choroid Plexus Produces CSF) * * * * * * • CSF flows from choroid plexus (cells that make CSF) • CSF vol ~125 mL, continuously produced with half life ~3 hr • CSF circulates and then returns to blood stream via arachnoid villi or granulations (absorb CSF)

36. Different Views of the Ventricles & Flow of CSF

37. CSF Flows Down Spinal Cord via the Central Canal

40. Anatomical Planes

41. Anatomical Planes

42. Anatomical Planes

43. Anatomical Directions

44. END – Lecture 02

48. The Cerebrum Central Sulcus separates frontal ( precentral gyrus ) from parietal ( postcentral gyrus ) Sylvian Fissure or Lateral Sulcus separates the temporal lobe from other lobes Sulci are fissures or grooves; Gyri are raised areas or outward bumps The Four Lobes of the Cerebrum

49. The Major Lobes of the Cerebrum The Cerebrum

52. Cross Section through the Cerebrum

53. The Cerebrum Anterior Commissure Note that the line from the label “Cerebral Cortex” at the upper left seems to point to white matter. However, the term Cerebral Cortex is generally used to refer to the Gray Matter.

54. Diffusion Tensor Imaging of Corpus Callosum Projections Diffusion Tensor Imaging involves a modified MRI magnet. It enables visualization of bundles of axons (the processes that transmit signals from one cell to another)

57. Schematic of Limbic Structures

58. Superior View of Limbic Structures Side View of Limbic Structures (without any other brain regions)

61. Location of the Basal Ganglia & Thalamus

64. Thalamic Connections with the Cortex

65. Thalamic Connections using Diffusion Tensor Imaging

66. Location of the Hypothalamus & Pituitary Gland

67. Location of the Hypothalamus & Pituitary Gland

72. Midsagittal view of Forebrain, Midbrain, & Hindbrain

73. Parts of the Forebrain, Midbrain, & Hindbrain

74. Human Brainstem

75. END – Lecture 03

80. PNS Transmits Information to the Body via 43 Pairs of Nerves • 12 pairs of CRANIAL NERVES – enter & exit the brain through holes in skull • 31 pairs of SPINAL NERVES – enter & exit the spinal cord between vertebrae

81. CRANIAL NERVES (12 pairs, CNs I through XII) • enter & exit the brain through holes ( foramena ) in skull • permit direct communication between brain & PNS • allow for sensory input from head, neck, upper abdomen • allow for motor output from brain to skeletal muscles in head and neck • allow for parasympathetic output to smooth muscles in head, neck, and upper abdomen • CNs I & II go to forebrain (prosencephalon) • CNs III & IV arise from midbrain (mesencephalon) • CNs V–XII enter & exit the hindbrain (rhombencephalon)

82. CRANIAL NERVES (12 pairs) 3 of the cranial nerves serve sensory functions only: • CN I (olfactory nerve) – sensory ; smell • CN II (optic nerve) – sensory ; sight • CN III • CN IV • CN V • CN VI • CN VII • CN VIII (auditory nerve) – sensory ; hearing • CN IX • CN X • CN XI • CN XII

83. Red is motor Blue is Sensory

84. CRANIAL NERVES (12 pairs) 3 of the cranial nerves control eye movement: • CN I (olfactory nerve) – sensory ; smell • CN II (optic nerve) – sensory ; sight • CN III (oculomotor nerve) – motor, eye movement • CN IV (trochlear nerve) – motor, eye movement • CN V • CN VI (abducens nerve) – motor, eye movement • CN VII • CN VIII (auditory nerve) – sensory ; hearing • CN IX • CN X • CN XI • CN XII

85. Red is motor Blue is Sensory

86. CRANIAL NERVES (12 pairs) 2 of the cranial nerves control facial muscles: • CN I (olfactory nerve) – sensory ; smell • CN II (optic nerve) – sensory ; sight • CN III (oculomotor nerve) – motor, eye movement • CN IV (trochlear nerve) – motor, eye movement • CN V (trigeminal nerve) – motor, chewing; sensory, face & head • CN VI (abducens nerve) – motor, eye movement • CN VII (facial nerve) – motor, facial muscles; sensory, taste & face • CN VIII (auditory nerve) – sensory ; hearing • CN IX • CN X • CN XI • CN XII

87. Red is motor Blue is Sensory

88. CRANIAL NERVES (12 pairs) 2 of the cranial nerves control throat and tongue muscles: • CN I (olfactory nerve) – sensory ; smell • CN II (optic nerve) – sensory ; sight • CN III (oculomotor nerve) – motor, eye movement • CN IV (trochlear nerve) – motor, eye movement • CN V (trigeminal nerve) – motor, chewing; sensory, face & head • CN VI (abducens nerve) – motor, eye movement • CN VII (facial nerve) – motor, facial muscles; sensory, taste & face • CN VIII (auditory nerve) – sensory ; hearing • CN IX (glossopharyngeal) – motor, throat & larynx; sensory, taste • CN X • CN XI • CN XII (hypoglossal nerve) – motor, tongue movements

89. Red is motor Blue is Sensory

90. CRANIAL NERVES (12 pairs) 1 cranial nerve wanders to the head, neck, & upper abdomen: • CN I (olfactory nerve) – sensory ; smell • CN II (optic nerve) – sensory ; sight • CN III (oculomotor nerve) – motor, eye movement • CN IV (trochlear nerve) – motor, eye movement • CN V (trigeminal nerve) – motor, chewing; sensory, face & head • CN VI (abducens nerve) – motor, eye movement • CN VII (facial nerve) – motor, facial muscles; sensory, taste & face • CN VIII (auditory nerve) – sensory ; hearing • CN IX (glossopharyngeal) – motor, throat & larynx; sensory, taste • CN X (vagus nerve) – motor, smooth muscles of neck, chest & upper abdomen; sensory, taste, organs of chest & upper abdomen • CN XI • CN XII (hypoglossal nerve) – motor, tongue movements

91. Red is motor Blue is Sensory

92. CRANIAL NERVES (12 pairs) 1 cranial nerve is motor only & innervates neck muscles: • CN I (olfactory nerve) – sensory ; smell (S) • CN II (optic nerve) – sensory ; sight (S) • CN III (oculomotor nerve) – motor, eye movement (M) • CN IV (trochlear nerve) – motor, eye movement (M) • CN V (trigeminal nerve) – motor, chewing; sensory, face & head (B) • CN VI (abducens nerve) – motor, eye movement (M) • CN VII (facial nerve) – motor, facial muscles; sensory, taste & face (B) • CN VIII (auditory nerve) – sensory ; hearing (S) • CN IX (glossopharyngeal) – motor, throat & larynx; sensory, taste (B) • CN X (vagus nerve) – motor, smooth muscles of thoracic & upper abdomen; sensory, taste, organs of chest & upper abdomen (B) • CN XI (accessory nerve) – motor only, skeletal muscles of neck (M) • CN XII (hypoglossal nerve) – motor, tongue movements (M) Mnemonic: S ome S ay M oney M atters B ut M y B rother S ays B ig B rains M atter M ore ( S = sensory; M = motor; B = both)

93. Red is motor Blue is Sensory

94. The Cranial Nerves & Their Functions Bell’s Palsy – facial paralysis caused by an infection of the facial nerve ( CN VII ). Results in paralysis on that side of face (not usually permanent).

95. PNS Transmits Information to the Body via 43 Pairs of Nerves • 12 pairs of CRANIAL NERVES – enter & exit the brain through holes in skull • 31 pairs of SPINAL NERVES – enter & exit the spinal cord between vertebrae

96. Spinal Nerves Exit the Spinal Cord Between Adjacent Vertebra

97. Spinal Nerves Exit the Spinal Cord Between Adjacent Vertebra

98. Spinal Nerves Exit the Spinal Cord Between Adjacent Vertebra

102. Dermatome Map • The body area innervated by one spinal nerve Q: Why do you not see C1 on the dermatome map to the right?

103. Sacral–Parasympathetic (anus, genitals, & bladder) Cranial–Parasympathetic (organs, vessels, and muscles, etc…) Thoracic & Lumbar – Sympathetic (organs, vessels, muscles, anus, genitals, bladder, etc…) Distribution of the Autonomic Nervous System

104. • thoracolumbar • craniosacral Distribution of the Autonomic Nervous System

105. END – Lecture 04

107. The Nervous System Two Types of Cells: 1. Neurons – cells of the nervous system 2. Glia – support cells Historically: • 1840 – Schleiden & Schwann proposed cells were basic units of tissue • However, scientists thought that nervous tissue was not made of cells 1860s Golgi – Silver impregnation 1892 Cajal – Neuron doctrine 1906 Golgi & Cajal were awarded the Nobel Prize Camillo Golgi (1843-1926) Ramón y Cajal (1852-1934)

109. Example of a Motor Neuron

110. Parts of a Neuron

111. Information Flow Between and Within Neurons 1. Signal enters dendrite or soma 2. Signal travels from soma to axon 3. Signal travels down axon 4. Signal leaves axon and enters dendrite or soma

112. Divergence (e.g., sensory) Convergence (e.g., motor) Information Flow Between Neurons

113. Basic Subcellular Components of Mammalian cells (similar for neurons)

114. Structure of Neurons

116. Cell Nucleus and Protein Synthesis Chromosomes contain genetic information, 23 pairs – 22 pairs are autosomal – the final pair are sex chromosomes (XX or XY) – the 23 pair of chromosomes contain ~20,000 to 25,000 genes Genome refers to the sum total of all the genes; same in every cell Nucleic acids are specialized compounds that contain a nitrogenous base, a sugar, and a phosphoric acid • Deoxyribonucleic acid (DNA ) encodes the genetic material of a cell – found in the nucleus (and in mitochondria) • Contains 4 nitrogen bases: Adenine, Guanine, Cytosine, Thymine • Nucleoside is nitrogen base + sugar (2-deoxyribose) • Nucleotide is base-sugar + phosphoric acid • Ribonucleic acid (RNA ) serves as blueprint for proteins – generally found in the cytoplasm as mRNA and ribosomes – also contain 4 nitrogen bases: Adenine, Guanine, Cytosine, Uracil – triplet base pairs encode specific amino acids (e.g., UGG = tryptophan ) – ribosomes read mRNA and add appropriate amino acids to make protein

117. Structure of Neurons

118. Examples of Genetic Alterations that affect Brain Function Fragile-X Syndrome – normally the X chromosome (FMR1 gene has a CGG triad repeated 10-30 times ) – in fragile-X, the CGG triad is repeated hundreds of times – produces mental retardation (disrupted synaptic connections) Mental retardation also results from untreated phenylketonuria (PKU) which is linked to an altered gene on chromosome 12 ( lack of phenylalanine hydroxylase ) Down Syndrome – Results from a trisomy of chromosome 21 (3 copies instead of 2) – leads to faulty brain development and cognitive impairments as well as other skeletal and soft tissue abnormalities

119. Classifying Neurons 1. Based on anatomical or morphological features (Ramón y Cajal) – unipolar (or monopolar) neuron – bipolar neuron – pseudo-unipolar neuron – multipolar neuron 2. Based on functionality (often used to describe neurons in the spinal cord) – motor neuron – sensory neuron – interneuron

120. Anatomical Classifications

121. Example of a Sensory Neuron Note: functionally, this pseudo-unipolar cell contains one axon (on the left) and a sensory process on the right, however this process is functionally an axon (it reliably transmits electrical spikes from the skin to the CNS). Only the sensory endings are technically dendrites. Warning: some people (including your text) refer to pseudo-unipolar cells as unipolar cells, I maintain a separate classification between these, however both are exclusively sensory neurons .

126. Glial Cells – Astrocytes

127. Myelination of Axons Schwann Cells (PNS) Oligodendrocytes (CNS) Value of myelination: 1. Speeds axonal transmission (action potential jumps from node of Ranvier to node of Ranvier instead of traveling down entire axon (Saltatory Conduction) 2. Assist in axon regeneration (Schwann cells only)

128. Electron Micrograph of a Schwann Cell Schwann Cells – myelinate only one segment of one axon

129. Comparison of Oligodendrocytes and Schwann Cells

130. Oligodendrocytes myelinate multiple segments of multiple axons

131. Blood-Brain Barrier

132. Blood-Brain Barrier

133. END – Lecture 05

135. Structure of Neurons

137. Cell Nucleus and Protein Synthesis Chromosomes contain genetic information, 23 pairs – 22 pairs are autosomal – the final pair are sex chromosomes (XX or XY) – the 23 pair of chromosomes contain ~20,000 to 25,000 genes Genome refers to the sum total of all the genes; same in every cell Nucleic acids are specialized compounds that contain a nitrogenous base, a sugar, and a phosphoric acid • Deoxyribonucleic acid (DNA ) encodes the genetic material of a cell – found in the nucleus (and in mitochondria) • Contains 4 nitrogen bases: Adenine, Guanine, Cytosine, Thymine • Nucleoside is nitrogen base + sugar (2-deoxyribose) • Nucleotide is base-sugar + phosphoric acid • Ribonucleic acid (RNA ) serves as blueprint for proteins – generally found in the cytoplasm as mRNA and ribosomes – also contain 4 nitrogen bases: Adenine, Guanine, Cytosine, Uracil – triplet base pairs encode specific amino acids (e.g., UGG = tryptophan ) – ribosomes read mRNA and add appropriate amino acids to make protein

138. Structure of Neurons

139. Examples of Genetic Alterations that affect Brain Function Fragile-X Syndrome – normally the X chromosome (FMR1 gene has a CGG triad repeated 10-30 times ) – in fragile-X, the CGG triad is repeated hundreds of times – produces mental retardation (disrupted synaptic connections) Mental retardation also results from untreated phenylketonuria (PKU) which is linked to an altered gene on chromosome 12 ( lack of phenylalanine hydroxylase ) Down Syndrome – Results from a trisomy of chromosome 21 (3 copies instead of 2) – leads to faulty brain development and cognitive impairments as well as other skeletal and soft tissue abnormalities

142. Synapse – the junction between two connected neurons (Sherrington, 1906) Synapse is composed of: 1. presynaptic membrane 2. synaptic cleft (<300 Å or 30 nm) 3. postsynaptic membrane Chemical Synapse During an impulse, or action potential, neurotransmitter vesicles fuse with the presynaptic membrane and release neurotransmitters into the synaptic cleft. They then diffuse across the cleft and bind to receptors on the postsynaptic neuronal membrane.

143. Electron Micrograph of an axodendritic synapse

144. EM of axodendritic synapse Mag: 280,000 X

147. Glial Cells and Neurons can communicate via Gap Junctions Gap junctions – enable electrical coupling between neurons and/or glial cells

148. Resting Membrane Potential (RMP) • Neurons are bathed in a salt solution (the salts dissociate into ions) • Ions are positive (cations) or negative (anions); e.g., NaCl dissociates into Na + & Cl - • Inside cell is more negative • Outside cell is more positive • cell membrane restricts ion movement • RMP is usually ~ -70 mV

150. Recording Neuronal Activity Much of what we know about the ionic basis of membrane potential and the action potential was learned using the Squid Giant Axon preparation.

151. Recording Neuronal Activity

152. Neuronal Cell Membrane is a Phospholipid Bilayer with Ion Channels Ions (salts) cannot simply diffuse across the cell membrane (they must go through channels) Hydrophilic (attracted to water) & Hydrophobic (repelled from water)

153. High Na + and Cl - outside (low inside) High K + inside (low outside) Distribution of Ions Across the Neuronal Membrane at Rest

154. What is the Equilibrium or Reversal Potential of an Ion?

155. Distribution of Ions Across the Neuronal Membrane at Rest 2 forces at work: chemical and electrical gradients

156. At Rest During Depolarization • Neuron’s RMP is negative at rest • During depolarization, Na + rushes into cell, making inside more positive • If depolarization is strong enough to fire an Action Potential, the inside will become much more positive than the outside Membrane Potential

157. • Small inputs are subthreshold (e.g., 1, 2, 3) • If input is large enough, threshold is reached. • At threshold, an Action Potential is initiated (e.g., 4) Relevant Concepts: • All-or-none law • absolute refractory period • relative refractory period The Action Potential

158. Summary of Ion Channel Activity During an Action Potential

160. Conduction of the Action Potential

161. Movement of an Action Potential down an Unmyelinated Axon

163. Saltatory Conduction – conserves energy; increases conduction speed (up to 120 m/s or 432 km/hr) Myelination

164. Saltatory Conduction IMPORTANT CONCEPTS: • Distribution of Na + & K + channels • Spread of electrical charge

165. Action Potential Propagation THOUGHT QUESTION: Is it better to have a previously myelinated axon become demyelinated or is it better to have an axon that was never myelinated in the first place? Or do they function the same?

166. The Na-K Pump ( 3 Na + : 2K + ) also called the Na-K ATPase Summary of Action Potential Events 1. During AP, Na + enters 2. After AP begins, K + exits 3. Cell must restore Na + & K + ! Na-K ATPase restores ion balance 1. 3 Na + ions are pumped out 2. 2 K + ions are pumped in

167. Coding of Stimulus Strength

168. 1. Temporal summation 2. Spatial summation How does a neuron integrate or add up inputs it receives?

169. Temporal and Spatial summation

170. Temporal and Spatial summation

171. END – Lecture 06

173. Four General Classes of Ion Channels

174. Movement of Sodium Ions with Channel Opening

175. Basic Steps involved in Transmitter Release

176. Before the action potential arrives, the postsynaptic ligand-gated channels are closed After the action potential arrives, neurotransmitter is released, binds and causes postsynaptic ligand-gated channels to open Ligand-Gated Ion Channel A B

177. Schematic of Synaptic Vesicle Release

178. Steps Involved in Neurotransmitter Release

179. Neurotransmitter Release & Reuptake

180. EM of Synaptic Vesicle Release

184. Movement of Major Ions (EPSPs vs IPSPs)

185. Postsynaptic and Presynaptic Inhibition Simple Rule of Thumb (each causes hyperpolarization of the membrane): Postsynaptic inhibition decreases a neuron’s responsiveness to inputs (acts at inputs) Presynaptic inhibition decreases a neuron’s ability to release transmitter (acts at output)

186. Balance between Excitation and Inhibition

188. IONOTROPIC RECEPTORS (e.g., nicotinic AChRs)

190. METABOTROPIC RECEPTORS Effects of Second Messenger Cascades, such as those through metabotropic G-protein-linked receptors, last longer than those through ionotropic ligand-gated receptors.

191. Agonists and Antagonists • Agonist activates the receptor • Antagonist blocks the receptor

192. Two Common Types of Agonists and Antagonists DIRECT INDIRECT Competes for same site as neurotransmitter ( competitive ) Does NOT compete for same site as neurotransmitter ( noncompetitive )

194. SUMMARY OF WAYS IN WHICH DRUGS CAN AFFECT SYNAPTIC TRANSMISSION Note: AGO = agonist ( blue Box ); ANT = antagonist ( red Box )

195. END – Lecture 07

197. Neurotransmitters and Neurohormones • Neurotransmitters – substances released by one neuron that bind to receptors on the target neuron e.g., acetylcholine note: some are referred to as Neuromodulators • Neurohormones – released by brain or other organs, travel via bloodstream to target neurons e.g., epinephrine (adrenal gland)

198. Neurohormone Release of epinephrine from the adrenal gland produces sympathetic arousal

200. Neurotransmitter Associated Neurons Acetylcholine cholinergic Dopamine dopaminergic Norepinephrine noradrenergic Serotonin serotonergic Epinephrine adrenergic Glutamate glutaminergic GABA GABAergic Anandamide cannabinergic Names of Neurons Associated with Specific Neurotransmitters

201. Acetylcholine • First neurotransmitter discovered (in PNS) • Most extensively studied neurotransmitter

202. Cholinergic Neurons 1. Dorsolateral Pons ––––––– REM sleep (including atonia) 2. Basolateral Forebrain –––– Activates cerebral cortex (nucleus basalis) facilitates learning & memory 3. Medial Septum ––––––––– Controls rhythms in hippocampus modulates memory formation

203. Synthesis of Acetylcholine Produced by combining the lipid breakdown product choline with acetyl-CoA (made in the mitochondria)

204. Synthesis of Acetylcholine

205. Enzymes Enzymes are proteins that catalyze a reaction that might normally take a long time to occur. If you see a word ending in “ –ase ” it’s an enzyme. The first word or part of the word (if it’s a one-word name) refers to what the enzyme is acting on. For example : • Choline acetyltransferase acts on choline to transfer an acetyl group and thus convert it to acetylcholine • Acetylcholinesterase acts on acetylcholine to break it up.

207. Cholinergic Receptors • Muscles contain nicotinic AChRs ( essential for rapid transmitter action at neuromuscular junction! ) • CNS contains both types, though mostly muscarinic AChRs ( nicotinic AChRs tend to be found at axoaxonic synapses )

208. Breakdown & Local Synthesis of ACh Acetylcholinesterase – Inactivates ACh after it is released (AChE) (breaks it into acetate and choline) Choline Re-uptake ––– Choline is transported back into the presynaptic terminal for local synthesis of ACh. Re-uptake is vital because axonal transport of choline from cell body is slow! Re-uptake has an efficiency of ~50% (i.e., about half of released is recovered)

209. Breakdown & Local Synthesis of ACh

210. Acetylcholinesterase ( located in the synaptic cleft ) breaks down acetylcholine into acetate and choline (which is recycled). Hemicholinium is a drug that inhibits the reuptake of choline. Reuptake has an efficiency of 50% (i.e., 50% is reused)

211. Drugs that Affect Cholinergic Receptors Examples 1. Curare • Blocks nicotinic AChRs (or nAChRs) • Had been and still is used by native South American populations • Used to paralyze muscles during surgery 2. Atropine • Blocks muscarinic AChRs (or mAChRs) • Used to treat AChE inhibitors (thus reducing the excess ACh action) • Also used to dilate the pupils for eye exams

212. Toxins that Affect Cholinergic Transmission Examples 1. Botulinum toxin ––––––––––––– Clostridium botulinum Prevents release of ACh thus it blocks muscle excitation VERY POTENT! (e.g., 1 oz can kill 200 million people!) 2. Tetanus toxin ––––––––––––––– Clostridium tetani Prevents release of Glycine & GABA thus it blocks inhibitory transmission indirectly causing excess ACh release Botulinum and Tetanus toxins cleave Synaptobrevin (thus preventing vesicle fusion & transmitter release) 3. Black Widow Spider Venom ––– Stimulates ACh release less toxic, but can be fatal in infants and elderly

213. Drugs that Affect ACh Breakdown Acetylcholinesterase inhibitors (AChE inhibitors) • Prolong the effects of ACh release by preventing its breakdown • Used as insecticides (insects can’t destroy it) • Used medically to relieve symptoms of myasthenia gravis (auto-immune) e.g., neostigmine - AChE inhibitor that can’t cross blood-brain barrier • Used as biological weapons e.g., Sarin, Tabun (treated with atropine sulfate , discussed earlier, and pralidoxime , which rejuvenates the AChE)

214. Summary of Cholinergic Drugs Drug Name Drug Effect Effect on Transmission Nicotine Stim nicotinic AChRs AGONIST Curare Block nicotinic AChRs ANTAGONIST Muscarine Stim. muscarinic AChRs AGONIST Atropine Block muscarinic AChRs ANTAGONIST Black widow spider venom Stim. ACh release AGONIST Botulinum toxin Block ACh release ANTAGONIST Neostigmine (can’t cross blood-brain barrier) Blocks acetylcholinesterase AGONIST Hemicholinium Blocks choline reuptake ANTAGONIST

215. Classification of the Monoamine Transmitters Catecholamines Indolamines Dopamine Serotonin Norepinephrine Epinephrine

217. Dopaminergic Neurons & Projections 1. Substantia Nigra ––––––––– to neostriatum , part of basal ganglia (involved in the control of movement ) 2. VTA ––––––––––––––––– to nucleus accumbens (involved in reinforcing effects of drugs of abuse ) to amygdala (involved in emotions ) to hippocampus (involved in the formation of memories ) 3. VTA ––––––––––––––––– to prefrontal cortex (involved in short-term memories , planning, problem-solving strategies) Nigrostriatal Mesolimbic projection Mesocortical projection

219. MAO (Monoamine Oxidase) – destroys excess monoamines – MAO-B is specific for dopamine – Deprenyl is an MAO-B inhibitor (depression, Parkinson’s) Reuptake – Transporters are used to remove Dopamine from the synaptic cleft and return it to the nerve terminal Regulation of Dopamine

220. Drugs that Affect Dopaminergic Transmission Examples 1. Monoamine oxidase inhibitors (MAO inhibitors) • MAO regulates production of catecholamines (destroys excess) • MAO inhibitors are used to treat depression • MAO-B is specific for dopamine (e.g., deprenyl) 2. Re-uptake inhibitors • Blocks re-uptake of dopamine by nerve terminals • e.g., amphetamine , cocaine , methylphenidate (Ritalin) Also causes release of DA & NE by reversing the direction of transporters Also blocks voltage-dependent sodium channels Used to treat ADHD

221. Examples of Drugs that Affect Dopaminergic Transmission 1. L-DOPA • Used to treat Parkinson’s disease • Crosses blood-brain barrier & enters CNS where it is converted to dopamine 2. AMPT (  -methyl-p-tyrosine) • Binds to tyrosine hydroxylase • Thus it prevents synthesis of L-DOPA and therefore dopamine 3. MPTP (methyl-phenyl-tetrahydropyridene) • Contaminant in synthetic Heroin • It’s metabolized into MPP+, which destroys dopamine neurons and produces Parkinson-like symptoms 4. Reserpine • Prevents storage of monoamines in synaptic vesicles • Acts by blocking transporters that pump monoamines into vesicles • End result is no transmitter is released

222. Effects of Drugs at Dopaminergic Synapses

223. Dopamine Receptors • DA receptors are metabotropic • 5 subtypes of DA receptors (D1 – D5) - D1 & D2 are the most common subtypes • Some are autoreceptors (similar to D2) located pre- and post-synaptic - postsynaptic – act to decrease neuron firing (K current) - presynaptic – act to suppress tyrosine-hydroxylase • Apomorphine has multiple effects on DA receptors - At low doses it binds presynaptic autoreceptors (decrease DA) - At high doses it acts as an agonist at postsynaptic D2 receptors

224. Schizophrenia • Serious mental disorder characterized by hallucinations, delusions, and disruption of normal logical thought processes • May involve hyperactivity of dopaminergic neurons ( excess ) 1. Chlorpromazine ( D2 antagonist ) alleviates hallucinations in schizophrenic patients 2. Clozapine ( D4 antagonist ) also relieves symptoms

225. Summary of Dopaminergic Drugs Drug Name Drug Effect Effect on Transmission L-DOPA Stimulate DA synthesis AGONIST AMPT Inhibit DA synthesis ANTAGONIST Deprenyl MAO-B inhibitor AGONIST Reserpine Block storage of DA in synaptic vesicles ANTAGONIST Amphetamine, Cocaine, Methylphenidate All 3 Block DA reuptake AGONIST MPTP Destroys DA neurons ANTAGONIST Clorpromazine Blocks D2 receptors ANTAGONIST Clozapine Blocks D4 receptors ANTAGONIST

226. Noradrenergic Neurons Locus Coeruleus (located in Reticular Formation) • Contains noradrenergic neurons whose axons extend to most of the brain, including thalamus, hypothalamus, limbic, cerebral cortex • Activation of LC increases vigilance or attentiveness to environment

227. Norepinephrine • Synthesized from dopamine • Synthesis actually occurs inside synaptic vesicles

229. Examples of Drugs that Affect Noradrenergic Transmission 1. Fusaric acid • Blocks DA-  -hydroxylase • Results in blockade of NE production in vesicles 2. Moclobemide • Blocks MAO-A (which normally destroys excess NE) • Results in an increase in NE 3. Desipramine • Blocks re-uptake of NE (and possibly serotonin) • a tricyclic antidepressant

230. Noradrenergic Receptors • NE receptors are called adrenergic because they respond to both norepinephrine (nor adren alin) and epinephrine ( adren alin) • Adrenergic receptors are metabotropic and coupled to G proteins • 2 types of adrenergic receptors are alpha (  ) and beta (  ) -  1 - and  2 -adrenergic (located in CNS & PNS) -  1 - and  2 -adrenergic (located in CNS & PNS) -  3 (located only in PNS) •  1 -adrenergic (slow depolarizing effect; more responsive to excitatory input) •  2 -adrenergic (slow hyperpolarizing effect) •  1 - and  2 -adrenergic are excitatory (they increase neuronal responsiveness to inputs).  1 are mostly on heart muscle whereas  2 are mostly on smooth muscle lining bronchioles & arterioles of skeletal muscle. Example of contraindications: beta-blockers & hypertension in asthmatics!

232. Summary of Noradrenergic Drugs Drug Name Drug Effect Effect on Transmission Clonidine – has a calming effect (but also interferes with learning) Yohimbine – has an agitating effect; promotes anxiety Clonidine Stimulate  2 receptors AGONIST Yohimbine Block  2 receptors ANTAGONIST Albuterol Stimulate  2 receptors AGONIST Butoxamine Block  2 receptors ANTAGONIST Fusaric acid Inhibits NE synthesis ANTAGONIST Reserpine Inhibits storage of NE in vesicles ANTAGONIST Desipramine Inhibits reuptake of NE AGONIST Moclobemide Inhibits MAO-A AGONIST

233. END – Lecture 08

235. Serotonin • Synthesized from the amino acid tryptophan • Important in the following: - regulation of mood - control of eating, sleep, arousal - regulation of pain ( hyperalgesia after injury) - control of dreaming

236. Serotonin • PRECURSORS to serotonin Dorsal Raphe –– sends 5-HT projections to cortex & basal ganglia • Medial Raphe –– sends 5-HT projections to cortex & dentate gyrus Note: raphe means “crease” or “seam” (the nuclei are found near the midline of the brain stem) The clusters of nuclei that make up the raphe are found in the medulla, pons, and midbrain.

237. Synthesis of Serotonin (or 5-HT) PCPA ( p -chlorophenylalanine) • blocks tryptophan hydroxylase and thus serotonin production MAO-A (monoamine oxidase A) • inactivates excess serotonin • ultimately converted into 5-HIAA ( measureable metabolite ) (5-hydroxy-indoleacetic acid)

238. Serotonin Receptors • 5-HT receptors are metabotropic ( except 5-HT 3 is an ionotropic Cl - channel ) • At least 9 different subtypes of 5-HT receptors - 5-HT 1A-1B ; 5-HT 1D-1F ; 5-HT 2A-2C ; 5-HT 3 - 5-HT 1B and 1D are presynaptic autoreceptors (axons) - 5-HT 1A are presynaptic autoreceptors (soma & dendrites) • 5-HT 3 are important in nausea & vomiting (antagonists help in chemo patients) Reminder: an autoreceptor is a receptor on its own axon terminal that responds to the neurotransmitter released by the same axon (a negative feedback mechanism)

239. Drugs that Affect Serotonin • 5-HT re-uptake inhibitors ( SRIs or SSRIs ) are useful in treating certain mental disorders (these drugs act by prolonging the action of serotonin at synapses) e.g., Fluoxetine (Prozac) - depression & anxiety disorders • Drugs that stimulate 5-HT release have also been used e.g., Fenfluramine – has been used as an appetite suppressant (in combination with phenteramine which acts on catecholamines to counteract the drowsiness caused by fenfluramine) • 5-HT 2A agonists cause hallucinations e.g., LSD is thought to exert behavioral effects as an agonist of 5-HT 2A receptors in the forebrain • Ecstasy ( MDMA ; 3-4 methylenedioxymethamphetamine ) causes release of serotonin, norepinephrine, and to a lesser extent dopamine (agonistic effect). MDMA damages serotonergic neurons .

240. Summary of Serotonergic Drugs Drug Name Drug Effect Effect on Transmission Fenfluramine Stimulate 5-HT release AGONIST Fluoxetine Inhibits reuptake of 5-HT AGONIST PCPA Inhibits 5-HT synthesis ANTAGONIST Reserpine Inhibits storage of 5-HT in vesicles ANTAGONIST

241. Summary of Neurotransmitter Synthesis Pathways PKU (phenylketonuria) - myelination - brain damage

242. Amino Acid Neurotransmitters Two Major Classes: excitatory and inhibitory 1. The Excitatory Neurotransmitter is Glutamate (in brain & spinal cord) 2. The Inhibitory Neurotransmitter is GABA (in brain) or Glycine (in spinal cord and lower brain)

244. NMDA Receptor Channel Complex 6 NMDAR Binding Sites 1. Glutamate (natural agonist) 2. Glycine (co-agonist required for glutamate to have any effect on NMDARs) 3. Mg 2+ (binds inside channel and blocks) 4. Zn 2+ (decreases activity) 5. Polyamine (increases activity) 6. PCP (blocks channel) Thus, the NMDA Receptor is a Voltage & Neurotransmitter-Dependent Ion Channel

245. Amino Acid Neurotransmitters GABA (MAJOR INHIBITORY TRANSMITTER IN BRAIN) • 2 main receptor subtypes ( 1 ionotropic & 1 metabotropic ) • [discussed further on next slide] GLYCINE (INHIBITORY TRANSMITTER IN CORD AND LOWER BRAIN) • ionotropic receptors (Cl – influx causes IPSPs) • strychnine is an antagonist (convulsions via excess/uncontrolled excitatatory drive)

246. GABA Receptors • Enzyme GAD (glutamic acid decarboxylase) converts glutamic acid to GABA - GAD is inhibited by allylglycine (thus blocking GABA synthesis) • GABA receptor subtypes: 1. GABA A • ionotropic • opens Cl – channel, causing Cl – influx and hyperpolarization • [see next slide for more details on GABA receptors] 2. GABA B • metabotropic (coupled to G-proteins) • causes K + efflux and thus hyperpolarization • Baclofen is an agonist (relaxes muscles)

247. GABA A Receptors GABA A Receptor has 5 binding sites 1. GABA (natural agonist) • muscimol is a direct agonist • bicuculline is a direct antagonist 2. Benzodiazepine (indirect agonist) • anxiolytic drugs (diazepam or valium) tranquilizers, promote sleep, reduce seizure activity, relax muscles 3. Barbiturate (indirect agonist) • low doses have a calming effect • rarely used as anesthetic due to small therapeutic index (easy to OD) 4. Steroid (indirect agonist) 5. Picrotoxin (indirect antagonist) Note:  -CCM (methyl-  -carboline-3-carboxylate) may be a natural ligand for Benzodiazepine binding site. This is an inverse agonist and thus produces fear, tension, and anxiety. It may be part of our fight or flight danger system.

249. END – Lecture 09

251. Development of the Human Brain Relative Brain Size: At birth: ~ 350 g At 1 yr: ~1000 g Adult: ~1200 g • Forebrain • Midbrain • Hindbrain

252. Timeline of Major Stages in Cerebral Cortex Development Neurogenesis declines significantly by week 20 and is nearly complete by 5 mo., but it does continue throughout life in some regions ( i.e., adult neurogenesis ).

253. Origin of Brain Cells Neurotrophic factors • EGF (epidermal growth factor) – stem to progenitor • bFGF (basic fibroblast growth factor) – progenitor to neuroblast • PDGF (platelet derived growth factor) – progenitor to glioblast (specifically oligodendrocyte)

255. Axon Pathfinding (how does an axon know where to go?) Roger Sperry (1943)

256. Axon Growth and Neuron Survival Growth Cones extend out as axons seek targets Tropic molecules guide axons; produced by targets (e.g., netrins) Trophic molecules support survival of cells and axons once target is reached neurotrophins (e.g., NGF, BDNF) Neuronal and synaptic pruning (via apoptosis) Important concepts : • Chemoattractant • Chemorepellent

257. Synapse Pruning (Elimination) Synaptic connections are plastic!

259. Regrowth of Axons • Can occur as long as the soma or cell body is intact • Rate is usually ~1 mm/day (PNS) • in CNS, axons usually regenerate only 1-2 mm total (CNS) , thus paralysis due to spinal cord injury is usually permanent • In PNS, axon regrowth follows myelin sheath back to target • Regrowth in PNS may not be perfect • e.g., if a motor neuron’s axon is cut (not crushed), segments may not align and axon may synapse on wrong target muscle

260. Collateral Sprouting

261. Denervation Supersensitivity Remember: Amphetamine causes DA release from existing axon terminals Apomorphine stimulates DA receptors (an appropriately high dose was used)

262. END – Lecture 10

264. Muscles and Muscle Fibers

265. 3 Types Muscle

266. Muscles and Muscle Fibers Skeletal Muscle : • Attach to bone or cartilage via tendons • Made up of cells (muscle fibers) • Each muscle fiber contains contractile proteins Actin – thin filaments Myosin – thick filaments • The filaments overlap

267. Major Components of Skeletal Muscle

268. Skeletal Muscle : • Striated appearance due to arrangement of actin & myosin • Actin filaments (thin) are attached to proteins that form the Z-line • Myosin filaments (thick) are found between rows of actin Sliding Filament Theory of Muscle Contraction • During contraction , the following events occur: 1. Actin filaments slide along each myosin filament (from both ends) 2. Z-lines get closer together (because actin is attached to Z-line) 3. Result is that the muscle shortens

269. Sliding Filament Theory

270. Neuromuscular Junction & Muscle Contraction : • Motor neurons innervate skeletal muscle fibers at a special region called the motor endplate • The motor endplate contains ACh receptors (mostly nicotinic) • One motor neuron can innervate multiple muscle fibers Motor Unit = motor neuron plus the muscle fibers it innervates • Muscles used for very fine (discrete) movements have smaller motor units • Muscles used for posture have larger motor units

271. Classification of Skeletal Muscles by Color : Red Muscle – High concentration of myoglobin (carries oxygen) – Relies heavily on oxidation to produce ATP – Engages in heavy activity without fatiguing – Used for slow, sustained movements – e.g., chicken or turkey legs White Muscle – Low concentration of myoglobin – Quickly goes into oxygen debt during contraction – Fatigues quickly – Used for rapid contractions in short bursts – e.g., chicken or turkey breasts Note: In humans and other mammals, red and white muscle fibers are found in the same muscles, unlike birds. For example, sprinting uses white, hiking/walking uses red.

272. Antagonistic Muscles (flexion and extension) Isotonic Contraction (muscle shortens) e.g., legs, produces the movement when carrying heavy box Isometric Contraction (muscle length stays same) e.g., back & arm muscles contract when holding or carrying heavy box Think of the different muscles that are used when carrying a heavy box up a flight of stairs – some contractions are isotonic and some are isometric. Muscular Movements and Contractions

273. Opposing or Antagonistic Muscle Movements Antagonistic Muscles (flexion vs extension)

274. Spinal Control of Movement REFLEXES are rapid movements mediated by either brain stem nuclei or the spinal cord (we’ll only cover spinal cord today). They are very Important (e.g., protect the body, basic life support) They vary in complexity and number of synapses: • Simple (e.g., withdrawal or flexion reflex) • Complex (e.g., postural, involving many different muscles) Note: Simple and Complex are relative terms. Even simple reflexes can involve MANY neurons (even thousands).

275. Three Reflexes Seen in Infants • Grasping • Babinski • Rooting

276. The Babinski Reflex – in children & adults it’s diagnostic of CNS damage • Positive Babinski – fanning of toes with stroking bottom of foot – always seen in infants < ~6 mo. (due to lack of descending inhibition) • Negative Babinski – curling of toes with stroking bottom of foot – seen in older infants and all healthy people – results from descending inhibitio n from brain

277. Withdrawal Reflex is a simple reflex involving only a few synapses between the sensory (afferent) neuron and the motor (efferent) neuron

278. Withdrawal Reflex (involves one or more interneurons between the sensory and motor neuron) Note: the more interneurons (and thus synapses) there are in the reflex arc, the longer the reflex takes

279. Withdrawal Reflex Note: descending projections from the brain can inhibit reflexes

281. Extrafusal fibers run the length of the muscle Intrafusal fibers do not run the length of the muscle and are located within the muscle spindle Note that the downward movement of the arm activates stretch reflex, which increases the strength of the muscle contraction and pulls the arm back up Monosynaptic Stretch Reflex

282. Examples • Patellar tendon reflex • Head bobbing upward when falling asleep while sitting in a chair Monosynaptic Stretch Reflex

283. Intrafusal muscle fibers Muscle Spindle – A few intrafusal fibers joined to a nuclear bag (inside the nuclear bag is a stretch receptor called the Annulospiral Receptor ). Axons from annulospiral receptor terminate onto motor neurons in spinal cord . Thus, stretching a muscle activates the annulospiral receptor which then stimulates extrafusal fibers to contract that same muscle. The Muscle Spindle (or annulospiral receptor) is vital for maintaining muscle tone Think of it like a “spring” located inside the muscle.

284. Gamma Motor Neurons Notice that if the muscle length changes due to muscle contraction (b) , the muscle spindle is “off line” and unable to respond to changes in muscle length. Activation of gamma motor neuron contracts the intrafusal fibers and thus “resets” the spindle so it can once again respond to stretch (c) .

285. Problem inherent in the stretch reflex • Contraction of one muscle would produce contraction of antagonist muscle • For example, the simple bending of the arm by biceps contraction (agonist) would cause the arm to straighten due to activation of the stretch reflex of triceps (antagonist) muscle Solution: Reciprocal Innervation (discovered by Sherrington). With reciprocal innervation, the axons of motor neurons that synapse on a muscle also branch and activate interneurons that inhibit motor neurons that synapse on the antagonist muscles.

286. Reciprocal Innervation Prevents the simple bending of an arm (biceps contraction) from causing the arm to straighten due to stretch reflex of the antagonistic triceps muscle

287. What if the muscle is contracting too vigorously? Golgi Tendon Organ Reflex is activated Golgi Tendon Organ (GTO) – stretch receptor found in the tendon – provides feedback to nervous system about muscle contraction – GTO fires when stretched – GTO axons synapse onto inhibitory spinal cord neurons – result of GTO activation is inhibition of the motor neuron – prevents damage to muscle as a result of excess contraction

288. Golgi Tendon Organ Reflex Think of the GTO like a “spring” located at each end of the muscle (in the tendon)

289. Proprioceptors (stretch receptors)

290. Sir Charles Scott Sherrington (1884-1935) • Studied many kinds of reflexes • Discovered reciprocal innervation • Introduced the term synapse • Principle of the Common Path – motor neuron is final common path for all movement • Principle of the Integrative Action of Neurons – all neurons in the body work together to produce smooth, precise movement – the crossed extensor reflex is an excellent example

291. Crossed Extensor Reflex • Withdrawal Reflex activated by sensory neuron synapsing onto interneuron, which excites motor neurons of the ipsilateral flexor • Interneuron also crosses over and synapses onto and excites the motor neurons of the contralateral extensor Example - if you step on a tack while walking, you’ll fall down without this reflex

292. END – Lecture 11

295. Motor Cortex & Motor Homunculus 1 2 3 4

297. The Lateral (Pyramidal) Motor System Originates in the Primary Motor Cortex (precentral gyrus) Axons of these Upper Motor Neurons project downward • through internal capsule • through medullary pyramids (hence name) • main branch crosses over at pyramidal decussation in medulla and descends through the contralateral spinal cord forming the lateral corticospinal tract

298. Lateral Corticospinal Tract • fine, directed motor control • hands, fingers, feet, toes • synapse directly onto motor neurons or indirectly via interneurons

299. Effects of Damage to Corticospinal Tract Damage to the Corticospinal Tract at any Level produces: 1. Initial loss of muscle tone ( atonia ) • transient flaccid paralysis immediately upon damage 2. Hyperactive deep tendon reflexes (myotactic) • hyperreflexia 3. Appearance of the Babinski sign ( positive Babinski ) • note: a positive Babinski may be seen during sleep or intoxication, and in infants <~6mo. Thus, appearance of a positive Babinski sign is diagnostic of pyramidal tract damage.

300. Effects of Cortical Damage to Lateral System Damage to the Premotor or Supplementary Motor Cortex or to parts of the Parietal or Temporal cortex produces Apraxia Apraxia “without action” – Difficulty carrying out purposeful movements, in the absence of paralysis or muscle weakness Apraxias are classified according to the systems affected: limb apraxia – movement (parietal lobe damage) (e.g., difficulty if asked to demonstrate a movement) oral apraxia – speech (Broca’s area damage) apraxic agraphia – writing (left parietal lobe damage if right-handed) constructional apraxia - drawing or construction (parietal lobe damage) (e.g., difficulty with spatial perception and execution) NOTE: Apraxias DO NOT involve damage to primary motor cortex or any other lower portions of the lateral motor system

301. Cortical Control of Movement Posterior association cortex is involved with perceptions Frontal association cortex is involved with plans for movement

302. Motor Neuron Disorders Muscular Dystrophy – muscle wasting • 30 different types, Duchenne’s MD is the most common - about 1 in 3-4000, typically between ages of 2 and 6 - due to defect in gene that encodes dystrophan - more common in boys (due to gene on X-chromosome) Myasthenia Gravis – degeneration of acetylcholine receptors at NMJ • results from an autoimmune response against AChRs • treated with immunosuppressants or thymectomy • treated with anticholinesterases (acetylcholinesterase inhibitors) • may also try plasmapheresis (filter the AChR-attacking antibodies from the patient’s blood) Amyotrophic lateral Sclerosis or ALS (Lou Gehrig’s disease) – motor neuron degeneration • degeneration of motor neurons in brain and spinal cord • progresses from muscle weakness to muscle wasting • no treatment • ~5,600 new cases each year, typically between ages of 40 & 70

303. The Medial (Extrapyramidal) Motor System Coordinates gross movements & postural adjustments • Develops before the pyramidal (lateral) system e.g., babies can play patty-cake before learning to hold a crayon • Develops at different times e.g., babies can hold head up before sitting upright

307. Location of the Basal Ganglia within the Forebrain

308. Damage to the Basal Ganglia Basal ganglia damage results in movement disorders Tics – brief, involuntary contractions of specific muscles Choreas – involuntary movements of head, arms, legs Huntington’s disease – uncontrolled tics and choreas early, dementia later – disruption of gene on chromosome 4 (excess CAG repeat) resulting in an abnormal Huntingtin ( Htt ) protein (with an elongated string of glutamine residues on it). The Htt mutation ultimately leads to death of GABAergic inhibitory neurons in the putamen (part of striatum) Parkinson’s disease – tremor, loss of balance, rigidity (hard to initiate movement) – caused by loss of dopaminergic neurons in substantia nigra

309. Relationship Between CAG Repeats and Age of Onset • CAG codes for glutamine • 11-24 CAG repeats is normal • >36 is linked to Huntington disease

310. Brain of Patient with Huntington’s Disease

311. Treatments for Parkinson’s Disease 1. Pharmacological Treatments L-DOPA – crosses blood-brain barrier and is converted to dopamine glutamate antagonists – reduce hyperactivity of glutamate in subthalamic nucleus 2. Destructive Surgical Treatments thalamotomy – surgical cut in ventral thalamus pallidotomy – surgical cut through the globus pallidus • both are thought to interfere with excitatory messages that produce symptoms • both reduce the rigidity and tremors (improving posture, gait, locomotion) • cognition and mood may also be improved with pallidotomy 3. Nondestructive Surgical Treatments subthalamic nucleus (STN) stimulation reduces symptoms • also called deep brain stimulation 4. Restorative Surgical Treatments fetal stem cell implantations – insertion of DA-producing cells from dead fetuses • raises serious ethical issues ( adult stem cells may be better, especially from same patient ) gene therapy – introduction of a gene that would rescue function • e.g., use virus to deliver GAD gene to STN, thus restoring lost inhibition

312. END – Lecture 12

314. Many Stimuli are Transmitted as Waves (e.g., electromagnetic radiation, vibration, and sound) The Electromagnetic Spectrum 1. Wavelength (nm, 1 nm = 10 -9 m) 2. Frequency (Hz, Hertz, cycles per s) 3. Amplitude (dB, decibels, range: 0 to 160) Wavelength ~380-760 nm is visible to humans Q: Why is the sky blue during day but reddish at sunrise or sunset?

315. v = ƒ  Electromagnetic Radiation (e.g., Light Waves) Relationship between velocity ( v ) , frequency (ƒ) , and wavelength (  ) of light can be described by the following equation: • Don’t worry about doing any calculations, this is just an example e.g., blue light with a wavelength of 455 nm (455 x 10 -9 m) would have a frequency of: ƒ = v /  ƒ = (3 x 10 8 m/s) / (455 x 10 -9 m) ƒ = (3/455) x 10 17 / sec ƒ = .00659 x 10 17 Hz ƒ = 659 x 10 12 Hz Notes: speed of light ( v ) is 3 x 10 8 m/s or 186,000 miles/sec m = meters; s = seconds nm = nanometers (10 -9 meters)

316. Stimulus Intensity is encoded by changes in action potential frequency Adaptation is a decrease in the firing rate in response to a continuous stimulus (e.g., odor perception decreases as you get used to it)

317. Distribution of Visual Receptors Why is this baby owl’s head nearly upside down?

318. The Visual System

319. The