Neuro Midterm 1 Learning Objectives

Prevailing Concepts of the Brain and its Function at Different Eras

1. Prehistoric Ancestors = brain is vital for life = cranial surgeries showed proof of trepanation (skull showed signs of healing)

2. Ancient Egypt = heart is the seat of the soul and memory (conscience and emotions), not the head as the brain was removed during mummification (lipids dissolve readily in natron and don’t conserve well)

3. Ancient Greece = Hippocrates Theory of Bodily Fluids (humours) = stirred by the heart = imbalance means disease

4. Roman Empire = as human autopsies were forbidden, Galen allowed animal experimentation to explore roles of the brain, cerebellum, ventricles

5. Renaissance = Middle Ages (Vesalius) performed human autopsies = fluid-mechanical theory and mind-brain problem

6. 16th and 17th Century = Discarded spirit-animal theory and discovered grey vs. white matter

7. Renaissance to 19th Century = Anatomical descriptions = went from bipartite brain (2 parts: left/right hemispheres) to 5 part brain

8. 19th Century = Central and Peripheral Divisions = Electrical Transmissions as NS can generate electricity = Localization of Function

Ancient Greece Theory of Bodily Humours

• blood = warm humour = heart

  • jovial, warm character

• pituitary = lymph, phlegm = brain

  • stolid, character (calm/dependable)

• yellow bile = liver

  • anxious character

• black bile = spleen

  • melancholic character (cold/dry)

Roman Empire Galen’s Discovery

• cerebrum = soft = sensations

• cerebellum = hard = muscle control

• ventricles

  • 4 humours = flow registers sensations and initiate muscle movements

  • nerves = conduits (channels) for the humours

Renaissance Fluid-Mechanical Theory

• animal spirits move through ventricles

• nervous system was there to help with fluid movement

Renaissance Mind-Brain Problem

• divine mind + material brain

• René Descartes = pineal gland is the seat of the soul

  • Cogito ergo sum = I think before I am

Anatomical Descriptions

• gyri = raised ridges or bumps on brain surface to increase surface area for more neurons

• sulci = shallow grooves between the gyri that help divide the brain into regions

• fissures = deep, wide grooves in the brain that separate larger sections or hemispheres of the brain

Pierre Flourens Experimental Ablation Method

• rabbits

• lesions = behavioral testing

• cerebellum involved in motor coordination

• however, his ablations were too global

Phrenology (Francis Gall)

• bumps on skull surface reflect brain surface = connected to personality traits

• based on comparison of different individuals

Broca’s Area (Paul Broca)

• observation of a patient having lost the power of speech following an accident to the head

• autopsy and localization of lesion = related to speech

Motor Areas

• Fritsch + Hitzig (dog)

  • electrical stimulation = movements

• ferrier (monkey)

  • ablation = paralysis

Visual Areas

• munk (animals)

  • ablations of the ocicipital lobe = vision loss

Phineas Gage

• personality change

• dynamite accident

• iron rod through frontal lobe

  • frontal ventro-medial damage

Natural Selection (Charles Darwin)

• nervous systems of different species may share common mechanisms

• adaptations is dependent on the type of species to their certain environment

Neuron: Reticular vs. Cellular

• reticular = diffused + spread out = controls basic functions (e.g. alertness)

• cellular = organized into specific regions = handles specialized tasks (e.g. sensory processing; motor control)

Controversy Debate

• AgNO₃ stain = to reveal structure

• reticular network theory = NS was continuous + interconnected web of neurons

• controversy = neuron theory

  • golgi staining method

  • argued neurons are separate cells that communicate at synapses

• neuron doctrine = cells are separate = theory accepted

Soup vs. Spark

• soup = chemical signalling

• spark = electrical signalling

• resolution = both work together = electrochemical model

Reductionist Approach: Levels of Analysis

• molecular

• cellular

• systems/networks

• behavioural

• cognitive

Challenges of Studying Neurons

1. size = 10-40 um = 1/5 of what they eye can see

2. obtaining nervous tissue that is sufficiently thin

3. neurons are generally colourless

Methods to Study Neurons

• neuron doctrine = histology

  • study of tissue structures

• nissl staining (cresyl violet)

  • stains nissl bodies (similar to ER) in the cytoplasm

  • revels only part of the whole cell

• golgi stain (AgNO₃) = revels 2 parts of neurons

  • soma or perikaryon or cell body

  • neurites = axons and dendrites

• microscopy = synaptic cleft is approx. 20nm (0.02 um)

  • optical microscope = 0.1 um

  • electron microscope = 0.01 nm

Parts of a Neuron + Function

• Soma

  • mitochondria = site of cellular respiration (O₂), Krebs cycle, ATP

• Axon

  • electric transmission of signal output

  • branches (collaterals) bifurcating at 90^o

  • hillock = initiation site of APs

• Nerve Terminal (vs Axon)

  • no micro tubules in terminal

  • presence of synaptic vesicle in terminal

  • abundance of membrane proteins (less in axons)

  • large number of mitochondria in terminal

• Synapse

  • synaptic transmission

  • electrical synapse = gap junctions

  • chemical synapse = neurotransmitter release

• Dendrites

  • processing info. received through synapses

  • spines responsible for learning and memory

• Cell Membrane

  • encloses cytoplasm = barrier

  • different regions have different membrane proteins

    • pre-/post-synaptic membranes

    • axonal membranes

  • supports electrochemical information transmission

• Cytoskeleton

  • internal scaffolding of neuronal membrane

  • 3 types of filaments

    • micro tubules

    • micro filaments (actin)

    • neuro filaments

• Glia = neuronal support

  • myelinated = insulation

Axoplasmic Transport

• anterograde = soma to nerve terminal

  • requires kinesins interacting with MTs

  • consumes ATP

  • used to visualize post-synaptic connection

  • labels nerve terminals

• retrograde = nerve terminal to soma

  • requires dyenins

  • consumes ATP

  • used to visualize pre-synaptic connection

  • labels cells that innervate target site

Neuron Classification

• number of neurites

  • unipolar

  • bipolar

  • multipolar

• cell morphologies

  • somatic = oral/spherical, pyramidal cells

  • dendritic = # of dendrites, length, branching pattern

• axon length

  • golgi type 1 = projection neurons

  • golgi type 2 = local neurons

• connectivity

  • sensory neurons = sensory receptors

  • motor neurons = muscle or gland

  • interneurons = contact other neurons within CNS

• secreted transmitter

  • cholinergic

  • gluamatergic

  • GABAergic

  • dopaminergic

  • serotoninergic

  • etc.

• function

  • excitatory

  • inhibitory

  • modulatory (both excites/inhibits)

  • N.B. neurotransmitter does not always equal the function

Glia

• astrocytes = star shaped projections

  • most numerous in the brain

  • fills space in between neurons

  • influences neurite growth

  • regulates ionic extracellular concentrations

  • shape synaptic transmission

• microglia

  • phagocyte

  • immune system

  • elimination of waste + dead cells

• compared to neurons

  • glia = insulate, support, nourish neurons, shape neuronal signalling

  • neurons = process info, sense environmental changes and communicates them to other neurons to command corporal responses

• myelinated glia

  • oligodendrocytes (CNS)

    • wrap around multiple axons

  • schwann cells (PNS)

    • wrap around single axons

  • insulate axons to speed up AP

• Node of ranvier

  • region where axonal membrane is exposed; high density Na channels

  • allows saltatory transmission

  • uninsulated

Neurons are Input-Output Machines

1. axons release inhibitory/excitatory NTs

2. transfer at synapse

3. increase action potential (neural code)

Movement of Ions

• diffusion

  • dissolved ions distribute evenly

  • ions flow down concentration gradient when:

    • channels permeable to specific ions

    • concentration gradient across the membrane

• electricity

  • electrical current flow across a membrane

  • Ohm’s law = (V = IR) or (I = gV)

  • electrical conductance (g) and resistance (R)

    • R = I/g

• driving force

  • high = more movement of solute from [high] environment to [low]

  • low = less movement of solute both ways

• distribution of ions across membrane = K+ is more concentrated on inside, while Na+ and Ca2+ are more concentrated on the outside

• Eq’m Potential = nernst equation

  • calculates the exact value of the eq’m potential for each ion in mV

Table for Ions and E ion at 37^oC

• K+ = -80mV

• Na+ = 62 mV

• Ca 2+ = 123 mV

• Cl- = -65 mV

Sodium-Potassium Pump

• Enzyme = breaks down ATP when Na is present

• Calcium pump = actively transports Ca2+ out of cytosol

Eq’m Potential (E ion)

• no net movement of ions when separated by phospholipid bilayer

• eq’m reached = K+ channels insert into bilayer

• electrical potential difference = balances ionic concentration gradient

• large changes in Vm = minuscale changes in ionic concentrations

• rate of movement of ions across membrane = proportional

Ionic Basis

• selective permeability of K+ channels

  • key determinant of resting membrane potential

• many types of potassium channel

  • amino acid sequences; family K+ channels

• K+ channels = 4 subunits

  • mutations = inherited neurological disorders

• regulating the external potassium concentration

  • blood-brain barrier

  • potassium spatial buffering