oberdick neuro3000 midterm 1 lecture 1-5 learning objectives

Be able to describe the different early views of the brain; how various scientists and philosophers understood the brain and know the general years

pre-enlightenment

trepanation (12,000 bce)

- anciently used for head injuries & spirit pulling

- today used for DBS & hydrocephaly

egyptians (3000 bce)

- thought HEART was seat of conciousness & key to soul bc dumped brain postmortem

- knew about brain damage bc helmets, aware of contralateralization, hieroglyph for brain

greeks (~500 bce)

- alcmaeon of croton: optic nerve + 4 senses (not touch), BRAIN was seat of conciousness, b4 hippocrates

- hippocrates: physician (Hippocratic oath), 4 elements linked to 4 humors (root of sickness); BRAIN was seat of conciousness; book 'corpus hippocraticum' talks abt seizures and contralateral projections

- aristotle: dad was physician he was philosopher/physicist, HEART was seat of consciousness and BRAIN cools blood

- herophilus: identified arteries/veins, father of anatomy, sensory/motor nerve observation, brain ventricle described, BRAIN is seat of consciousness

Describe how the current understanding of the basic brain anatomy and function evolved, what was learned about electrical conduction and localization of function

romans (early ce)

galen/aelius galenus: physician, structure/function animal dissection and patient observations, sensation& memory ctrl by cerebrum bc soft while muscles ctrl by cerebellum bc hard, early version of ventricular fluid mech. model of spirit flow, 7/12 cranial nerves, input/output of brain

the renaissance

andreas vesalius: anatomy artist, BRAIN is seat of consciousness, more mechanical model than galens, pons & hippocampus namer

rene descartes: hydraulic model, nerves are hollow and carry vital spirits that were pumped by pineal gland and inflated muscles(physical explanation of behavior), mind-brain dualism, empirical scientific method

the enlightenment

- less emphasis on religion, more on concrete science "sapere aude" dare to know based on observation

- 1800s: pns and cns known, same basic brain structure/localization, nerves-white matter project-gray matter

- galvani: electrical stimulation makes contractions

- reymond and bernstein: nerve AP, didn't know mechanism

- hemholtz: found that nerve AP is slower so not like electricity

- nerves don't have animal spirits for movement, it uses electrical properties

- phrenology is BS and doesnt explain localization

- broca's area is localization example

- localization is monoist view (opposite of mind-brain dualism)

- complex behaviors are as much distributed as much as they are localized

- fritsch and hitzig: induced movement by stimulation of specific areas

- penfield and rasmussen: inhibition and activation at the same time, motor homunculus

Describe how animal models have been used in neuroscience and the basic principles of animal use in research

animals have been used to revolutionize all areas of neuroscience by answering questions easily and efficiently with tools that nature provides

- hodgkin and huxley: giant squid axon bc large axon to record AP

- kandel: aplysia bc simple reflex pathway with large neuron circuit for isolation

- brenner: c elegans bc simple cell makeup to do genetic analysis w connectome map

- monkeys were used for visual system bc simular to humans

- rates and mice were used for somatosensory/olfactionbc good whiskers and olfaction

the three r's of research w animals:

1. replacement - dont use animals if possible

2. reduction - minimize amount of animals needed in experiment (use stats to estimate # of animals needed intially)

3. refinement - no pain/harm, improve welfare

Describe the basic structures of the neuron and how they are identified

neuron- chem/electrical circuit driving brain function over long distances; studies through golgi (random neurons) and nissl (rough ER) stains

soma (cell body): nucleus for DNA to protein/ctrl by histone acetylation & dna methylation, and subcellular organelles, mitochondria for ATP 20%/NT release/apoptosis/Ca2+ homeostasis, ribosomes for mRNA/tRNA translation to proteins, ER smooth for lipids for cell membrane (stays inside cell), ER rough for mRNA release/nissl shows this, golgi for tagging/trafficking, RER+golgi= somatodendritic domain extension

dendrite: treelike receiving projections, # of branches biforcating distinguishes, synaptic plasticity, RER+golgi= somatodendritic domain extension for proteins used there, can use distal pools of mRNA, morphology affect synaptic transmission related to neuro diseases

axon: long extension from soma, transmit AP propogating from axon hillock, collaterals bifurcate off main, varicosities are early transmission of NT, terminal buttons store and release neuro chemicals, presynaptic, needs a way to traffic molecules bc no rough ER+golgi

cytoskeleton: outer shell of it all ctrl shape/traffic, microtubules (tubulin) are long tracks for cargo up/down axon+dendrites/ant uses kinesin ret uses dynein, actin microfilaments (actin) for cell shape/plasticity/local tracks for cargo of synapse/myosin motor, neurofilaments (neurofilament) control diameter of axon/signal propagation/goes on microtubule tracks

Explain the basic structure and function of the synapse

chemical transmission btwn neurons is at synpase

tripartite synapse:

axonal end presynaptic -- synaptic cleft -- dendritic end postsynaptic

hugged by astrocyte for reuptake, held bby neuroligins

Describe how neurons are classified

1) neurite number: unipolar (sensory), bipolar (retina, olfactory), multipolar (most neurons)

2) shape of dendritic tree: pyrimidal (spiny) and stellate cells (half and half spiny)

3) connectivity: sensory (sensory receptors to brains), interneurons (local neuron connection), projection neurons (long neuron connection), motor neurons (brain to muscle)

4) chemistry: Nt and enzymes used to make them, gene expression

Describe the basic structure and function of different types of glial cells

- Oligodendrocytes:

myelin insulation, metabolic support by 1 on 1 but multiple nodes, regenerative, CNS

- Astrocytes:

hug synapse, regulate excitibility/transmission, injury sends proteins for brain repair, transports H2O, brain tumor bc division, feet for BBB

- Microglia:

nervous system injury, resident immune cell of CNS, moniters electrical activity and prunes connections, phagocytizes cells,

- Schwann cells:

myelinates 1 acon (internode region), scar tissue, peripheral axon regeneration, PNS

Understand the basic electrical concepts - resistance, conductance, voltage, current, and how ion movement is controlled

Resistance: how hard it is for an electric charge to move, inverse of conductance; R, ohms = 1/g; think myeline

Conductance: how easy it is for an electric charge to move, inverse of resistance: g, siemens; think myelin

Voltage: aka electrical potential, measures the force (diff btwn 2 points, more dif means more current); E measured in Volts, V; think charge

Current: amount of charge moving thru conductor/unit of time depends on CONDUCTANCE + VOLTAGE; Ohm's Law ~ all are proportional to each other, if one=0 then the rate is 0

Ion Movement: impermeable to cell membrane; the current depends on chemical gradience and electrostatic attraction; at RMP K+ high inside Na+ high outside; must pass through protein channels that open and close under different circumstances

Refresh knowledge of the basic structure of cell membrane and proteins

-semipermeable

-fluid mosaic model

-glycolipids and glycoproteins embedded within

-protein channels help pass things thru- quaternary protein complex has multiple subunits created by tertiary folding

Be able to describe the concept of equilibrium potential, resting potential, and be able to apply it

resting potential: comparing inside vs outside of NONACTIVE neuron; potential Vm = -65mV inside; negative bc A- inside and Na+ kind permeable, no open ion channels, more + ions outside

equilibrium potential: when electrochemical tendencies balance out for an ion, sometimes they are opposite! EK+ = -80mV high inside, small number makes big difference; ENa+ = +62, counterbalancing electrical potential

ionic driving force: proportional difference of membrane potential Vm and equilibrium potential Eion

Understand the Nernst and Goldman equations, be able to apply them

Nernst Equation: used to calculate equilibrium potential, assumes channel for specific ion is open; =Eion

Goldman Equation: considers 2+ channels relative permeabilties, like resting neuron has open K+ and Na+ leak, otherwise RMP would be -80mV=EK+; AP driven by Na+ permeability increase inward

RMP maintained thru 321Nokia pump replenishing leak channels and is voltage independent

Voltage gated/dependent ion channels are responsible for AP, at the axon hillock

Be able to explain how AP are produced

local potentials are excitatory/inhibitory, are graded and combine to form AP

EPSP depolorizes and can cause AP, neuron gets more + influx

IPSP hyperpolarizes and inhibits AP, neuron gets more - influx

can be spatial or temporal summation, and can 'cancel' each other out

Understand how APs are propogated down the axon

steps: all or nothingg! subthreshold membrane potentials don't lead to AP!

1) AP made if depolarization collects at axon hillock and reaches threshold of -55mV (more positive)

2) Na+ influx til about +40mV

3) peak positive causes K+ to efflux (more negative)

4) afterhyperpolarization to about -80mV bc tons of K+

5) RMP restoration

6) NT release at axonal terminal

greater frequency can initiate another AP during RELATIVE refractory period; not absolute

multiple things can affect propagation of AP down axon like diameter and myelination etc.

Understand how APs are recorded

- electrode intracellularly

- electrode extracellularly near cell/s

-hodgkin and huxley used voltage clamp to see how ion permeability changes through an AP; showed Na+ influx, K+ efflux

- outward current/driving force = positive; inward current/driving force = negative

- firing frequency/pattern diversity encodes unique neuronal function

Be able to explain how Ohm's law and equilibrium potentials relate to AP

use Ohm's Law of electrochemistry proportions to calculate driving force difference= Vm - ion or current=gion(Vm-Eion)

driving forces

Na+: neg rmp and high extracellular Na+; -65-62)=-127 mV; greatest effect from threshold to rising bc driving force and conductance is changing

K+: pos membrane potential and high intracellular K+; +40-(-80)=+105mV; greatest effect from peak to lowering

driving for

Understand the basics of how voltage-gated Na+ and K+ channels work

(voltage sensor, gating, selectivity, etc.)

There is a sensor on the protein (positive stretch ) when membrane potential gets more positive, the positive stretch part on protein 'moves' to open, and it is selectively permeable to the specific ion, and then it has to close and be able to reopen again

patch clamp technique used to record current of single channel; can suck and hold or break it off. unless let loose to refresh, wont go back to RMP and reopen

Na+ voltage channel; selectivity filter large enough for Na+ and H2O; linkers has inactivation gate like a ball (III-IV linker) caused by activation of voltage sensor (-55mV opens channel pore moving sensor), ball wont be taken out until RMP deactivate inactivation gate (absolute refractory period) and voltage gate is back open; 1 protein with 4 subunits

K+ voltage change; it is a delayed rectified, gets things back, lots of variety bc 4 dif proteins creating subunits; inactivation stays for a while, doesn't open right away and needs a higher potential to open, has plus charge sensor like Na+

There are a variety of animal venoms and toxins that can be used to study the pharmacology of the nervous system

different chemicals can be used to block specific channel types

label sites and source***, can use these sources to investigate

ex. Na+ and K+ channel blockers were used to investigate AP in squic axon

There are many channelopathies caused by pathological variants (mutations) in the genes encoding voltage dependent ion channels

things like epilepsy caused by mutations in these genes that encode voltage dependent ion channels, causing more to come in etc and causing electrical imbalance

Na+ channelopathies:

Nav or SCN most cause epilepsy

K+ channelopathies:

KCN, epilepsy, ataxia, paralysis,