DEVELOPMENT I: PROLIFERATION, MIGRATIONTodays reading: Chap. 7(178-195); 23(690-698) Wednesday: Chapter 23 (698-708)AMHERST COLLEGE INTRODUCTION TO NEUROSCIENCE MONDAY, FEBRUARY 4, 2008 Neuroanatomy questions What is an exception to the rule that ganglia are in the PNS?Place in rostro-caudal order:Inferior colliculusThalamusMedullary respiratory centerThe medial forebrain bundle is, as the name suggests, a bundle of axons in the medial forebrain . Why isnt it called the medial forebrain tract?

Tomorrow - 7:00 AM to 8:00 PMBangs Community Center(Behind Panda East & Raos)

Outline of development

Neuroscience 26 AMHERST COLLEGE Spring, 2008

INTRODUCTION TO NEUROSCIENCE

Profs. Sarah Turgeon and Steve George

Course Outline and Readings

Date

Topic

Reading

Introduction

January 28

Introduction to neuroscience

Chapter 1

30

SG

Approaches to studying brain and behavior

Chapter 2

February 1

ST

Outline of neuroanatomy

Chapter 7 (168-180; 193-199; 205-235); Chapter 15 (490-497)

Development of the nervous system

4

SG

Neurogenesis, migration

Chap. 7 (178-195); 23 (690-8)

6

Axon pathfinding; cell death

Chapter 23 (698-708)

8

Role of neural activity in development

Sheetz AJ, Williams RW, and Dubin MW Severity of ganglion cell death during early postnatal development is modulated by both neuronal activity and binocular competition. Visual Neuroscience 12 (1995) 605-610.

Electrical signalling

11

Membranes and membrane potentials

Chapter 3

13

Action potential

Chapter 4

15

Conductance mechanisms

Stringer JL. Regulation of extracellular potassium in the developing hippocampus. Developmental Brain Research 110 (1998) 97103.

Synaptic transmission

18

Chemical and electrical transmission

Chapter 5 (102-122)

20

Postsynaptic potentials; neural integration

Chapter 5 (122-131)

21/22

Exam 1

25

ST

Neurotransmitter systems

Chapter 6; Chapter 15 (498-507)

27

Castner SA, Xiao L, Becker JB. Sex differences in striatal dopamine: in vivo microdialysis and behavioral studies. Brain Research 610 (1993) 127-134.

29

Morgan DG et al. Divergent changes in D-1 and D-2 dopamine binding sites in human brain during aging. Neurobiology of Aging 8 (1987) 95-201.

Sensory Neuroscience

March 3

SG

Vision: transduction; receptive fields

Chapter 9 (288-306)

5

Visual information processing

Chapter 10 (310-329)

7

Visual cortex Chapter 10 (324-348)

Ferster D, Chung S, Wheat H. Orientation selectivity of thalamic input to simple cells of cat visual cortex. Nature. 380 (1996) 24952.

10

Visual plasticity; critical periods

Chapter 23 (708-716)

12

Somatosensory system

Chapter 12 (388-408)

14

Pain Chapter 12 (408-421)

Eisenberger NI, Lieberman MD, Williams KD. Does rejection hurt? An FMRI study of social exclusion. Science. 302 (2003) 290292.

[Spring break]

24

ST

Chemoreception Chapter 8

Curtis KS, Contreras RJ. Sex differences in electrophysiological and behavioral responses to NaCl taste. Behavioral Neuroscience120 (2006) 917-924.

26

Auditory system

Chapter 11 (344-375)

28

Auditory system II

Wu H.-C. et al. Influence of auditory deprivation upon the tonotopic organization in the inferior colliculus: a Fos immunocytochemical study in the rat.

Eur. J. Neuroscience 17 (2003) 2540-2552

Sensorimotor control systems

31

Spinal mechanisms

Chapter 13

April 2

Brain mechanisms Chapter 14

Perese DA, Ulman J, Viola J, Ewing SE, Bankiewicz KS. A 6-hydroxy-dopamine-induced selective parkinsonian rat model. Brain Research 494 (1989) 285-293.

3/4

Exam 2

Neural basis of behavioral plasticity

7

SG

Human and animal memory

Chapter 24

9

Cellular mechanisms of neural plasticity

Chapter 23 (716-722); Chap. 25

11

Clem RL, Tansu C, Barth AL Ongoing in vivo experience triggers synaptic metaplasticity in the neocortex. Science 319 (2008) 101-104.

Neuroendocrine and motivational systems

14

ST

Endocrine systems

Chapter 15 (482-490); Chapter 17

16

Bado C, Rissman EF. Androgen receptor is essential for sexual differentiation of responses to olfactory cues in mice. Eur. J. Neuroscience25 (2007), 2182-2190.

18

JPB

Feeding behavior

Chapter 16 (510-527)

21

ST

Stress I

Chapter 18 (573-582); Ch 22 (668-670)

23

Stress II

Yaka R et al. Effect of varied gestational stress on acquisition of spatial memory, hippocampal LTP and synaptic proteins in juvenile male rats.

Behavioural Brain Res. 179 (2007) 126-132

24/25

Exam 3

Diseases of the nervous system

28

Addiction Chap.16 (504-507; 522-527)

Box 16.5 p. 526

Cruz FC, Marin MT, Planeta CS. The reinstatement of amphetamine-induced place preference is long-lasting and related to decreased expression of AMPA receptors in the nucleus accumbens. Neuroscience 151 (2008) 313-319

30

ST

Depression Chapter 22 (673-679)

Hattori, S., et al. Enriched environments influence depression-related behavior in adult mice and the survival of newborn cells in their hippocampi.

Behavioural Brain Res. 180 (2007) 69-76

May 2

Biochemical basis of neurodegenerative diseases: Huntingtons and ALS

Guest Lecture: Dr. Robert Ferrante Box 14.3 p. 468

5

Schizophrenia Chapter 22 (679-685)

Flagstad P, Glenthoj BY, Didriksen M. Cognitive deficits caused by late gestational disruption of neurogenesis in rats: a preclinical model of schizophrenia. Neuropsychopharmacology 30 (2005) 250-260.

7

SG

Alzheimer disease Box 2.3 p. 36-37

Verret L, Jankowsky JL, Xu GM, Borchelt DR, Rampon C. Alzheimer's-type amyloidosis in transgenic mice impairs survival of newborn neurons derived from adult hippocampal neurogenesis. Journal of Neuroscience 27 (2007) 6771-80

9

Review /catchup session [+ Neuroscience Senior Thesis presentations]

Final exam: 3-day take home, due during finals period

2

ProliferationFertilized egg Whole organism (single cell)1011 neuronsQuestion: how many rounds of cell division?2x2x2x2x. = 10x10x10x.x10Log10(2)=3.3, i.e.10 = 23.3, so 1011=(23.3)11= 236

ProliferationFertilized egg Whole organism (single cell)1011 neuronsQuestion: how many rounds of cell division?

Early vertebrate developmentNeural groove neural tube. Vertebrate CNS = hollow organFig. 7.8

Early vertebrate developmentNeural groove neural tube. Vertebrate CNS = hollow organFig. 7.8

Vertebrate brain development: 3 subdivisions Anterior neural tube 3 brain vesiclesFig. 7.9, 7.10, 7.13Basal Line of Thalamusganglia secondary fusion

Vertebrate development: 3 brain subdivisions Anterior neural tube 3 brain vesiclesFig. 7.9, 710

Development of the retina

Retinal ganglion cells develop after the optic cup is formed. Their axons grow from the retina to the diencephalon and midbrain.Is optic nerve a consistent name for the bundle of axons connecting the retina to the rest of the brain? Is ganglion cell a consistent name for neurons in the retina?Fig. 7.10,11

Features of proliferationCell divisions occur in ventricular zone

Nucleus moves to marginal zone for S phase (synthesizing DNA for next division)

Cell becomes postmitotic (has its birthday) after horizontal cleavageFig. 22.2

Features of proliferationFig. 22.2

1. Technique: Autoradiography3H = tritium, hydrogen atom with 2 extra neutrons; it undergoes radioactive decay3H -thymidine (a nucleotide that is one component of the genetic material, DNA) is used to study cell birthdays (i.e. date of final cell division) 3H-proline, an amino acid that is one component of proteins, is used to trace neuronal pathways.

1. Technique: Autoradiography

Analysis of cell birthdaysLabel monkey fetus with 3H-thymidine at E33 or E56Wait until animal matures, then perform autoradiographyPiaVentricleExposed to label at E33Exposed to label at E56Conclusion:Postmitotic neurons migrate towards the pia, migrating past neurons that migrated previously.

Analysis of cell birthdaysLabel monkey fetus with 3H-thymidine at E33 or E56Wait until animal matures, then perform autoradiographyPiaVentricleExposed to label at E33Exposed to label at E56

Technical question: When a monkey fetus is exposed to 3H-thymidine at embryonic day 33, shouldnt all dividing cells take up the label, including cells whose progeny will be dividing later, e.g. at day 56? In that case, why is there only a narrow band of label in the animals exposed at day 33 why doesnt it extend all the way up to the pia?Exposedat E33Exposedat E56

Features of mammalian cortical developmentDividing neuroblasts proliferate in the ventricular zoneAt some point (before birth in mammals) cells stop dividing i.e. they have their birthday, except for a very few neuronal stem cells They immediately migrate towards the marginal zone, following radial glial cellsThe order of migration is inside out, i.e. newly born neurons migrate past previously migrated ones to a point nearer the piaLarge neurons are born earlier than small neuronsGlial cells retain the capability of dividing throughout the life of the animal

Neurons and the cell cycleAre neurons able to divide, or are they post-mitotic?(Mitosis = cell division; post-mitotic = can no longer divide)Look for mitotic figures in slices of brain tissueBut, theres a problemModern methodsAutoradiographyBromodeoxyuridine (BRDU)

Neurons and the cell cycleAre neurons able to divide, or are they post-mitotic?

2. BRDU + specific neuron labelGreen=BRDURed=neuron-specific stain

Neuronal differentiation: Control of gene expressioncytoplasmnucleusmembranecytoplasmnucleusmembrane

Neuronal differentiation: Control of gene expression

AMPAdenosine monophosphatecAMPCyclic AMPCBPCREB binding proteinCREBcyclic AMP response element binding proteinKinaseEnzyme that adds a phosphate to another moleculePKAProtein kinase APol II Polymerase II enzyme that transcribes DNA into RNAPO4PhosphateTATAsequence of thymidine, adenine, etc. that binds Pol II

cytoplasmnucleusmembrane

Introduction to cell death2 3 times overproduction of cells during developmentOccurs in many parts of the bodyTwo distinct kinds:Programmed (apoptotic, suicide) Necrotic (murder)In invertebrates, specific identified cell always dies at a particular timeCell death program can be activated in adults, e.g. neurodegenerative diseases