Foundations I Fall, 2017 Prof. J.M. Tepper Aidekman 109F X 3618 - - PowerPoint PPT Presentation

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Foundations I Fall, 2017 Prof. J.M. Tepper Aidekman 109F X 3618 Course Organization Brief History of Neuroscience Intro to Neurocytology Foundations I (26:112:565:01) Fall 2017 Course coordinator: Vince McGinty (vince.mcginty@rutgers.edu)

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Foundations I Fall, 2017

Prof. J.M. Tepper Aidekman 109F X 3618

Course Organization Brief History of Neuroscience Intro to Neurocytology

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Foundations I (26:112:565:01) Fall 2017

Course coordinator: Vince McGinty (vince.mcginty@rutgers.edu) Tuesdays and Thursdays (10:00-12:30). All classes in Room 202. TAs: Hussein Khdour (hussein.khdour@rutgers.edu) Required books: Liqun Luo’s “Principles of Neurobiology”; Watson’s “Molecular Biology of the Gene” DATE TOPIC READINGS TYPE Lecturer Sept 19 Historical Introduction; Basic Neurocytology, Synaptology Notes Physiol Tepper Sept 21 NO CLASS (ROSH HASHANAH) Sept 26 Development of the Nervous System Luo’s Chapter 7 + Notes Tran Sept 28 Overview of Neurophysiological Methods; Basic Concepts in Electrical Circuitry Notes Physiol Tepper Oct 3 Ionic Basis of the Resting Membrane Potential Luo’s Chapter 2 Physiol McGinty Oct 5 Ionic Basis of the Action Potential Luo’s Chapter 2 Physiol McGinty Oct 10 No Class Oct 12 No Class Oct 17 Structure and Function of Voltage-Gated Ion Channels Luo’s Chapter 2 Physiol McGinty Oct 19 Synaptic Transmission I: General Overview, NMJ, quantal release, presynaptic mechanisms Luo’s Chapter 3 Physiol McGinty Oct 24 Synaptic Transmission II: Pharmacokinetics & Pharmacodynamics Notes Pharmacol Abercrombie Oct 26 Synaptic Transmission III: Structure and Function

f Ligand-Gated Ion Channels; Ionotropes and

GPCRs Notes Pharmacol Abercrombie Oct 31 Review session with TAs Nov 2 Exam Nov 7 Synaptic Transmission IV: CNS Transmitters I – Amino Acid Transmitters Notes Pharmacol Abercrombie Nov 9 Synaptic Transmission V: CNS Transmitters II – Biogenic Amine Transmitters; Neuromodulators and Auto and Hetero-receptors Notes Pharmacol Abercrombie Nov 14 No Class (SFN Meeting) Nov 16 Synaptic Transmission VII: Pre and postsynaptic Mechanisms of Synaptic Plasticity Luo’s Chapter 10 + Notes Physiol Pare Nov 21 Structure of nucleic acids, chromosome structure, genome, replication genes and basic genetics, mechanisms of replication. I Watson et al., (see hand-out) Molecular Biology Koos Nov 23 No Class Nov 28 Mechanism of transcription, and translation, posttranslational modification, RNA splicing, non protein-coding genes and RNA interference I Watson et al., (see hand-out) Molecular Biology Koos Nov 30 Mechanism of transcription, and translation, posttranslational modification, RNA splicing, non protein-coding genes and RNA interference II Watson et al., (see hand-out) Molecular Biology Koos Dec 5 Regulation of gene expression, epigenetics Watson et al., (see hand-out) Molecular Biology Koos Dec 7 Methods for regulating transgene expression, or for interfering with gene expression Watson et al., (see hand-out) Molecular Biology Koos Dec 12 Designer methods for regulating or reporting neuronal function and structure, optogenetics, DREADDs Watson et al., (see hand-out) Molecular Biology Koos Dec 14 Review session with TAs Dec 19 Exam

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Foundations I (26:112:565:01) Fall 2017

Course coordinator: Vince McGinty (juvm430@newark.rutgers.edu)) Tuesdays and Thursdays (10:00-12:30). All classes in Room 202

TA: Hussein Khdour (hussein.khdour@rutgers.edu)

Required texts: Liqun Luo’ s “Principles of Neurobiology”; Watson’ s “Molecular Biology of the Gene”

2 exams – mostly objective – MC, fill-in TF , matching etc. best way to study is a) lecture notes b) handouts, c) assigned readings TA hours/meetings by arrangement, use them any time, as often as you like Must maintain B average in Foundations to maintain good standing in Program

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A brief (and biased) history of neurophysiology

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Ancient Egypt

c. 3300 B.C.E.

Canopic Jars

liver lungs intestines stomach

The function of the brain is to produce snot brain hook

mummification

The heart was considered to be the seat of intelligence and reason

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Alcmaeon of Crota (5th Century B.C.E.)

“The brain is the seat of intelligence and sensation….”

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Aristotle (384-322 B.C.E.)

Plato Aristotle

“...every animate being is a living thing which can move itself only because it has a soul.”

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René Descartes (1596-1650)

“Cogito ergo sum” founder of analytic geometry law of refraction conservation of momentum Cartesian coordinates

polymath - an expert/genius in many different fields

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René Descartes (1632)

pineal controls release of animal spirits from the ventricles hollow nerve animal spirits flow down the nerve and inflate the muscle, causing contraction

“..animals respond to external stimuli.”

Traite de l’homme (1664) The Royal gardens at Saint Germain-en-Laye

particles of fire excite skin and tug on little threads connected to the pineal

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Luigi Galvani (1791)

animal electricity

"Therefore having noticed that frog preparations which hung by copper hooks from the iron railings surrounding a balcony of our house contracted not only during thunder storms but also in fine weather, I decided to determine whether or not these contractions were due to the action of atmospheric electricity...Finally....I began to scrape and press the hook fastened to the back bone against the iron railing to see whether by such a procedure contractions might be excited, and whether instead of an alteration in the condition of the atmospheric electricity some other changes might be effective. I then noticed frequent contractions, none of which depended on the variations of the weather. ”

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Alessandro Volta (1793)

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Voltaic Piles

no animal electricity!- external electrical stimulation from a battery!

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Hans Christian Oersted (1820)

Advances in science often occur by leaps and bounds as a result of the discovery of new technologies The invention of the galvanometer - April 21, 1820

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Leopold Nobili (1825)

improved the galvanometer by adding a second winding in the

pposite direction to cancel out interference

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Johannes Müller (1826)

“Law of Specific Nerve Energies”

‘... the kind of sensation following stimulation of a sensory nerve does not depend on the mode

f stimulation but upon the nature of the nerve itself...’

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Carlos Matteuchi c. 1840

“injury current”

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Emil DuBois Reymond (1845)

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Emil DuBois Reymond

“The motor nerve is not stimulated by the absolute value

f the current-density at any given moment, but by its

variations from one instant to another, and the effect produced by these rapid changes increases with their rapidity and their greatness in a given time.”

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Emil DuBois Reymond

“If I do not greatly deceive myself, I have succeeded in realizing in full actuality (albeit under a slightly different aspect) the hundred years’ dream of physicists and physiologists, to wit, the identity of the nervous principle with electricity.”

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Herman Von Helmholtz (1850)

first measurement of action potential propagation inferred synaptic delay theory of color vision place theory of pitch perception Law of Conservation of Energy

another polymath

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Richard Caton (1875)

recorded “...feeble currents of varying direction...” from surface

f the skull

Stay away from low profile journals!! EEG

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neuronal syncitium

Camillo Golgi (1843-1926)

Nobel Prize in Physiology and Medicine, 1906

“reazione nera” - the black reaction, i.e. Golgi Stain the Golgi Apparatus

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Santiago Ramon y Cajal (1852-1934)

Nobel Prize in Physiology and Medicine, 1906

neuron doctrine law of dynamic polarization synapses

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“As nature, in order to assure and amplify the contacts, has created complicated systems of pericellular ramifications (systems which become incomprehensible within the hypothesis of continuity), it must be admitted that the nerve currents are transmitted from one element to the

ther as a consequence of a sort of induction or influence

from a distance.”

S. Ramon y Cajal, Nobel Lecture, 1906

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“It may seem strange that, since I have always been opposed to the neuron theory - although acknowledging that its starting-point is to be found in my own work - I have chosen this question of the neuron as the subject of my lecture, and that it comes at a time when this doctrine is generally recognized to be going out of favour...”

“...I shall therefore confine myself to saying that, while I admire the brilliancy of the doctrine which is a worthy product of the high intellect of my illustrious Spanish colleague, I cannot agree with him on some points of an anatomical nature...”

C. Golgi, Nobel Lecture, 1906

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Sir Charles Sherrington (1857-1952)

“In view therefore, of the probable importance physiologically of this mode of nexus between neurone and neurone it is convenient to have a term for it. The term introduced has been synapse.” - C.S. Sherrington, 1906

Nobel Prize in Physiology and Medicine, 1932

synaptic vesicles synaptic cleft

presynaptic axon terminal postsynaptic dendrite

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Otto Loewi (1873–1961)

"The night before Easter Sunday, I woke, turned on the light and jotted down a few notes on a tiny slip of paper. Then I fell asleep again. It occurred to me at six

'clock in the morning that during the night

I had written down something most important, but I was unable to decipher the scrawl. Nobel Prize in Physiology and Medicine, 1936 The next night at three o'clock, the idea

returned. It was the design of an

experiment to determine whether or not the hypothesis of chemical transmission that I had uttered seventeen years ago was correct. I got up immediately went to the laboratory and performed a simple experiment on a frog heart according to the nocturnal design."

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Hodgkin and Huxley

Nobel Prize in Physiology and Medicine, 1963

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Giant Squid

voltage clamp amplifer quantitative description

f ionic currents

Just kidding Giant Squid up to 13-14 m long

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Eccles and Sherrington, 1936

Sir John Eccles (1903 -1997)

Nobel Prize in Physiology and Medicine, 1963

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Sir John Eccles (1903 -1997)

Nobel Prize in Physiology and Medicine, 1963

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Neher and Sakmann

Nobel Prize in Physiology and Medicine, 1991

Erwin Neher Bert Sakmann

patch clamp recording

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The Nobel Prize in Chemistry 2008 Osamu Shimomura Martin Chalfie Roger Y. Tsien "for the discovery and development of the green fluorescent protein, GFP".

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Introduction to Neurocytology

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Introduction to Real Neurocytology

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spiny dendrites aspiny dendrites

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local axon collaterals soma/cell body dendrites

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2.3 µm

nucleus nuclear indentation nucleolus

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presynaptic bouton postsynaptic dendrite

active zone

Parts of a synapse

synaptic vesicle large dense core vesicle mitochondrion

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pleomorphic vesicles

Gray’s Type II (symmetric)

small round vesicles

Gray’s Type I (asymmetric)

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Gray's type I (asymmetric, 30 nm cleft, small [30-40 nm] round vesicles) = excitatory, usually made onto the heads of dendritic spines, dendritic shafts or occasionally, somata. Gray's type II (symmetric, 20 nm cleft, small or pleomorphic vesicles) = inhibitory, almost never

n the heads of dendritic spines, often spine shafts, dendritic shafts, or somata.

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large (40-50 nm) d e n s e c o r e vesicle small (30-40 nm) electron lucent vesicle

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Axoaxonic synapse

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Axoaxonic synapse

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Dendrodendritic synapse Somatodendritic synapse

Olfactory bulb

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