Neuro 3000 Exam 1

scientific method

-observation, replication, interpretation, verification

-driven by hypotheses, but research needed

-scientists are still subject to bias (see what they're expecting)

Early Views

-most believed the heart controlled the body

-prehistoric brain surgery told us that they knew the importance of the brain

Early Views: Egypt

-5000 years ago

-know about brain damage

-had hieroglyph for brain

-heart controlled soul and memories

-discarded brains and preserved bodies

Early Views: Hippocrates

-brain = center for sense and intelligence

-epilepsy = brain disorder

Optic Nerve first described

-500 BC

-by Alcmaion of Crotona

Early Views: Plato

-387 BC

-brain = mental process center

Early Views : Aristotle

-384-322 BC

-heart = intelligence center

-brain cooled blood

Early Views: Major Theory

four humors (vital fluids) controlled body

Early Views: Galen

-130-200

-similar to Hippocrates

-dissected and tried to determine brain function

-cerebrum = soft = sense and memory

-cerebellum = tough = muscle

(right for wrong reasons)

-brain receives sensory information

-nerves = hollow tubes & carry humors (laster 1500 years)

-humors = in ventricles

-learned from gladiator injuries and animal dissections

Early Views : Da Vinci

wax cast of ventricles in 1504

Early Views: Vesalius

drawing of the brain 1514-1564

Early Views: Descartes

-fluid mechanical theory

-abilities = from "mind" that talks to brain via pineal gland

-1596-1650

17th & 18th Century views

-white matter = fibers that make up nerves and bring info to and from grey matter

-peripheral (rest) vs. central (brain & SC) NS

-general bump (gyri) and groove (sulci & fissure) patterns on brain

19th Century views

-injury = death, disrupted thought, movement, and sensation (ablation studies)

-brain communicates via nerves

-different parts have different roles

-works like a machine and follows nature's rules

19th Cent: Galvani & Bois-Reymond

-electricity = stimulate movements

-nerves = wires

-electricity = generated in the brain

Bell & Magendie

-nerves = fiber bundles

-each fiber goes one way

-sensory and motor in the same budles

Bell

-motor fiber = from cerebellum

-sensory = to cerebrum

Fluorens ablation experiment agrees

Phrenology

-created by Gall in 1809

-Fluorens thought all cerebellum = all functions (wrong) but proved phrenology wrong

Broca

-different functions for different areas of brain

-lesioned = understand but not talk ("tan")

Fritsch & Hitzig

-1870

-specific region controls movements

-electrical stimulation in dog and frog

Removal of area = paralysis in monkeys (Ferrier 1881)

Munk

occipital lobe required for vision

Willis

animals display basic human behaviors

Darwin

-1859

-origin of species

1. organisms evolve over time

2. common ancestors

3. more species over time

4. evolution is gradual

5. natural selection

Species for studying

-different brain area sizes between species

-some are good for certain studies because of outstanding features, convenience, comparison, preservation, economics, or to treat diseased

Examples:

-squid/snail = neurons, synapse, plasticity

-cat/primate = vision

-rodent = neuropharm & behaviors

-worm (C.elegans) = aging & development

-fruit fly = synapse formation

-zebrafish = development & drug screening

Animals in Research

-smallest possible # used ; mostly rodents

-major discoveries have been made

-animals benefit as well

-welfare = tightly regulates (sometimes better than ours)

-consider alternatives, anesthesia used, only minimum # used, and review committees

-animal rights = life of animal = human life

Alzheimer' Disease

-degeneration of cholinergic neurons

-dementia

-fatal

Parkinson's Disease

-degeneration of dopaminergic neurons

-loss of voluntary control

Depression

-30 million experience it

-major suicide cause

schizophrenia

-2 million affected

-severe psychotic illness

-delusions

-hallucinations

-bizarre behaviors

spinal cord injury & autism

major neuro disorders as well

stroke

loss of blood supply leads to permanent damage to function

epilepsy

seizures due to disruption of normal brain electrical activity

multiple sclerosis

loss of nerve condition

how do neurons and glia compare in numbers?

about equal (85 billion each)

-more neurons in the cerebellum

-more glia in the cerebrum

neuron size

0.01-0.05 mm in diameter

-that is 40-200 times smaller than a pencil tip

-couldn't be studied until late 17th century

Early studies of neurons

-need to "fix" brain to make rubbery instead of pudding like

-used microtome to slice very thin

-need to stain because brain is cream colored

Nissl Stains

-stains the nuclei of all cells

-neurons have way more rough ER and ribosomes (Nissl bodies) to stain therefore you can see them better

-1894

Golgi Stains

-stains entire neuron of some neurons

-changed view of neuron

-one axon=output ; many dendrites = input

-communicate with 5-10 K neurons

Cell Theory

-Schwann (1839)

-all tissues are made of cells

Golgi's hypothesis

-reticular theory (nerve net)

-neurites are fused together like the circulatory system

-i.e. nervous system = exception to cell theory

Cajal's hypothesis

-said neurites are not continuous, but communicate by contact

-created the Neuron Doctrine (cell theory applies to nervous system)

-father of neuroscience

Neuron structure

-same organelles as other cells ; differences in distribution

-soma = cell body = same as other cells

-splicing is also more prevalent in the brain

DNA microarrays

-used to identify unique gene expression in different regions of the same brain or different brains

-two samples labeled with different colors

-put into wells with a gene specific sequence

-color determines which sample has a reduced expression of the gene

-could have 30 K wells for genome study

Neuronal Specification

-cell types have complex molecular composition

-defined by neuron specific combination of genes (makes the different types)

-all cells have same genes, just different combos

-many genes in neurons are expressed in non-neural genes as well

-alternative splicing is wide spread and conserved in the brain

Copy Variation

-each neuron may have a different variation when it is copied

-sequencing genome of individual neurons

-aneuploid (less/more) and subchromosomal CNV

-13-41% have at least one CNV

-a subset of neurons is especially prone to large scale genome alterations

-could have implications for neural function

-neurons with different genome could have different phenotype

Endoplasmic Reticulum in neurons

-Nissl bodies = rough ER and ribosomes

-there are a lot because the make a lot of proteins

-ribosomes on ER make membrane bound proteins

-free ribosomes make free proteins

Mitochondria in neurons

-many proteins imbedded

-protein composition varies from dendrites, soma and axon

Neurofilaments

-cytoskeleton

-diameter = 10 nm, 100 um long

-also called intermediate filaments in other cells

-strong and maintains shape of neuron

-forms tangles in AD

-axial

-not polar

-not tracks (transport)

-filling ; if cell lacks, then slow conduction

Microtubules

-cytoskeleton

-long range (350 um) , diameter = 20 nm

-tubulin polymer

-tracks, not static, axial, polar

-other proteins (MAPs): one tau found on paired helical filaments in AD tangles

Microfilaments

-cytoskeleton

-diameter = 5 nm ; shortest

-numerous in neurites (terminal and spines)

-2 thin strands of actin polymers make it

-not static (still)

-longitudinal in cell and close to membrane

-axial & radial , polar, tracks (help move vesicles maybe?)

axon

-unique to neurons

-no ER ; very few ribosomes

-some mRNA and miRNA (regulates RNAs) = for growth

-some translation is mature axons possible

-proteins differ than in soma

-1 mm - 1 m long

-diameter = 1 um (humans) to 25nm

-squid diameter = 1 mm

-speed is determined by the diameter (thick = fast)

axon hillock

controls what goes down axon

-begins AP

-has many Na channels

what are the branches on an axon called

collaterals

terminal bouton

-at end of axon

-some have terminal arbor (branches)

-no microtubules

-many vesicles

-protein rich

-many mitochondria

boutons en passant

synapses mid way through axon

synapse

-cleft = space between pre and post synaptic neurons

-transmission is mediated by a chemical neurotransmitter

-many drugs/chemicals act here

-malfunctions here are responsible for many mental disorders

Wallerian Degredation

-after axon is cut, everything distal (after) dies

-clue to transport occurence

Slow axonal transport

-1-10 mm a day

-cystolic protein movement

-found by Weis (like a hose?)

fast axonal transport

-400-1000 mm a day

-carries cargo in vesicles

-membranous organelles

-found by Pulse Labeling

anterograde axonal transport

-walked down mictotubule

-uses kinesin (motor protein)

-uses ATP

-some to bouton

retrograde axonal transport

-dynen used (motor protei)

-goes along microtubules

-50-250 mm/day

-macromolecules are in vesicles

-pinocytotic or endocytotic vesicles

-uses "old" mitochondria

Weiss

studied accumulation

-build up on soma side shows that there is transport in one direction

Pulse Labeling

-Grafstein

-label AA radioactive

-feed to neuron

-see how long it takes to move

Imaging transport

-GFP (green fluorescent protein) or other labeled proteins in cultured neurons

-some confocal imaging in vivo preps

Studying transport

-vesicles, mitochondria, and organelles move

-fast and slow differ due to time cargo is actually moving

Using Retrograde:

inject HRP and in 2 days, will travel past soma and show what projects to the area

Using anterograde:

label a NT and see where it goes

Dendrites

-tree= the collection of all branches from the soma

-different shapes and sizes

-covered in 1000s of synapses

-some have spines (aspinous = no spines)

-spines can change structure and amount of input

-polyribosomes under the spines with mRNA present for protein synthesis

-contains microtubules and few microfilaments

Unipolar

also called pseudo-unipolar

-single process with peripherial branch and central branch

-found in sensory glia

bipolar

-found in sensory structures

-i.e retina ad olfactory bulb

-two branches off of soma ; one axon & one dendrite

multipolar

-many dendrites

-single axon

-majority of neurons

Classes of dendrite structure in the cerebrum

pyramidal (multipolar typical) or stellate (blob)

-all pyramidal are spiny

-some stellate are aspinous, some are spiny

neuron connectivity

-sensory = take info in

-motor = sends info out

-interneurons = connect the others ; most of these

Golgi Type I

-type of axonal length

-projection neurons

-extend between brain regions

-long axons

-many pyramidal cells

Golgi type II

-type of axonal legth

-local circuit neurons

-connect to others in the vicinity

-short axon

-stellate cells

Neurotransmitters

-over 100 peptide NT

-determined by enzymes, antibodies, etc.

-acetylcholine, gluatamate, GABA, serotonin, dopamine, opiods, peptides, etc.

Gene expression in neurons

-different types of neurons express specific sets of transcripts

-changes in cell transcriptome (combo of everything) during wiring

-cell types have complex molecular composition defines by neuron specific combo of genes

(combo is what matters, not how many)

-can use RNA sequencing to identify

Glia & non-neural cells

-equal # to neurons

-supportive of neural function , stem cells, and support synapse function

-astrocytes = most numerous

-myelinating = schwann and oligodendrocytes

-micro glia = immune- like

-ependymal cells = line vesicles, direct migration during development

micro glia

-remove debris (phagocytosis)

-release cytokines

-may be activates in response to stoke or trauma

-may be involves in purining or refining circuits

-sends signal to signal body immune cells

astrocytes

-looks like a star

-tightly packed between neurons (20 nm between them)

-express NT receptors and release gliotransmitters (ex: glutamate receptors)

-humans have more than rats and the are larger and more ramifies (more projections)

-rats improved when given human ones (proof of importance for our abilities)

-regulates content of extracellular space (remove NT from cleft (uptake) ; regulate ion levels (release K during AP))

-can divide (major sources of tumors - gliomas) more easily than neurons

Tripartate synapse

astrocytes on either side of the cleft

Homosynaptic modulation

-elementary Ca response

-NT activates astrocyte and increase Ca levels

-releases GT back onto same synapse

Heterosynatic modulation

-integrated Ca response

-more activated

-released GT onto another synapse

Territorial modualtion

-global Ca repsonse

-activated by more than one synapse and releases GT to all possible areas

myelin

fatty coating

-speeds AP

oligodendrocytes

-brain and spinal cord (CNS)

-one cell myelinates several portions of several axons

Schwann cells

-peripheral nervous system (PNS)

-myelinates single portion of single axon

-ONE cell = between nodes

Nodes

not myelinated areas with many Na channels to keep AP propagating down axon

-could only be microns long

speed of AP varies by:

-signal

-myelin amount

-length

-etc.

passive conduction

-only works for short distances

-cannot make it all the way down a longer axon

action potential

-conducts signal without loss of strength

-required to send fast signals long distances

-needs excitable cells to generate

-briefly reverses the RMP (-65, +40, -65)

-voltage reverses, not concentration of ions

resting membrane potential (Vm)

-needed inn order to have AP

-is negative inside compared to outside at rest (ours=-65mV)

-RMP varies between types of neurons

-always more K inside and more Na outside cell

-use microelectrode to measure

RMP generation

-cytosol and etracellular each have specific ion concentrations and compositions

-plasma membrane = high resistance when channels closed (no leaks)

-membrane acts as a capacitor (holds charge by keeping K inside)

-the membrane proteins/channels are specific to where on the neuron they are located

cytosol & extracellular fluid

-water = major component

-ions are surrounded by "sphere of hydration"

-cations = + ; anions = -

-Na,K,Ca,Cl are important for neurophysiology

water's use in/around cells

-it is polar with covalent bonds

-dissolves polar molecules

-ions and polar molecules = hydrophilic (water loving)

-molecules with nonpolar covalent bonds = hydrophobic (water hating) EX: fats, oils

phospholipid membrane

-forms barrier to H2O and ions

-allows membrane potentials to form

Phospholipid bilayer:

-hydrophillic head toward H2O outwards

-hydrophobic tails inward

-relatively thin

protein structure

-properties of every cell are determined by the types of proteins expressed in the cytosol and membrane

-20 AA ; properties determined by R group

-chains of AA (polypeptide) are held together by peptide bonds

-protein = 1+ polypeptide

-structure is determined by its function

Folding order:

primary (AA) to secondary (alpha helix or beta pleated sheet) to tertiary (3D) to quaternary (multiple proteins)

ion channels

-have hydrophobic and hydrohillic regions

-selective

-can be controlled by gate

pumps

-transport ions across membrane against concentration gradient

-uses ATP for energy

ion movement

controlled by diffusion and electrical forces

diffusion

-random movement from high to low concentrations to balance (concentration gradient)

-is temperature dependent

-must have a path through the membrane (i.e channel)

Electrical Current (i)

-movement of charge to balance charges

-positive attracted to negative

-positive = in direction of positive charge movement

Current flow depends on:

-electrical potential (voltage (V))

-electrical conductance