Foundations

Neuroscience

the scientific study of the nervous system

stems from a wide range of perspectives

considers human nature, behavior, and capability as mediated by the nervous system

Society for Neuroscience

largest professional neuroscience society

Prehistoric Ancestors’ Understanding of Neuroscience

knew the brain was vital to life and often targeted it during hunting and battles

performed skull surgeries on live patients who lived

Trepanation

making holes in skulls

perhaps to provide as escape route for evil spirits or to attempt to dissect out mental illness of to permit examination of the brain

skulls showed signs of healing

Ancient Egypt’s Understanding of Neuroscience

heart as seat of soul and memory, not head

heart preserved after death, brain removed and discarded

Ancient Greece’s Understanding of Neuroscience

recognized structure/function relationship in nervous system

Hippocrates and the Brain

earliest proponent of modern thinking about the brain

recognized that the brain was involved in sensation and was likely the seat of intelligence

views were not widely shared

Aristotle and the Brain

brain as a radiator to cool blood overheated by the activity of the heart and the rest of the body

Galen

physician to the gladiators who saw and treated many severe injuries

performed many careful animals dissections

recognized general regions

attempted to deduce structure/function relationship for these major lobes on the basis of physical consistency

describes ventricles but believes them to be associated with humors

Renaissance to 17th Century Neuroscience

anatomists added much detail to our understanding of nervous system gross anatomy but little functional information or interpretation

fluid-mechanic model persisted

philosophical thought and interpretation was developed during the Renaissance, including much that involved what we now know to be neural properties/functions

Descartes

influential mathematician and philospoher

believed in fluid-mechanic model

higher cognitive abilities of humans was believed to stem from the mind which was thought to be a spiritual rather than physical entity

Mind-Body Problem

whether or not there is a connection between our consciousness and the brain

one entity of separate

17th and 18th Centuries Neuroscience

anatomists began modern investigation of the brain and nervous system and began to describe in increasing detail the different lobes and regions of the brain

as microscopic and staining techniques developed, more and more of the cytoarchitecture structure of the nervous system was described

increasingly detailed description and mapping of: central vs. peripheral nervous tissue, gray matter vs. white matter, primary nerves leading to/from the central nervous system, the beginnings of identification of neural subregions on the basis of cellular structure

18th Century Neuroscience

recognized that the general pattern of cerebral gyri (ridges) and sulci (grooves) could be seen across individuals and could be related to distinct and common features

distinction between the anatomy and function of the brain/spinal cord was becoming more clear as was the relationship between the peripheral and central nervous systems (injury and ablation)

medical and scientific pursuit of biological knowledge was supported and cultivated

19th Century Neuroscience

recognition of nerves as conductors of electricity and of nervous tissue having electrical properties

careful experiments by Bell and Magendie demonstrated that dorsal and ventral spinal nerve roots carry different information in opposite directions

severing any one nerve root was shown to lead to a loss of either sensory or motor function at a distinct location on just one side of the body

most nerves consist of many individual nerve fibers some of which are efferent/motor and some of which are afferent/sensory

 much progress was made at refining what was known about the localization of function in the brain

experimental work in animals expanded to include a variety of additional species (providing comparative material) and to include new techniques, especially that of experimental stimulation

more-refined description of the cells of the nervous system (neurons) and their many processes

not yet known how neurons communicated or whether individual neurons are physically fused to their neighbors

advancement of a general cell theory to describe tissue development and organization supported these advances in understanding neural structure

Charles Bell

recognized that the cerebellum is the origin of motor fibers and that the cerebrum is the destination of sensory fibers

Franz Joseph Gall

father of phrenology

Phrenology

incorrect assumption that bumps of the surface of the skull thought to reflect brain surface and related personality traits

Marie-Jean-Pierre Flourens

used experimental ablation method to identify regions of motor and sensory processing

Paul Broca

anatomist who catalogued human behaviors and post-mortem neural pathology

described a discrete region of the human cerebrum for speech motor function (area named after him)

recorded speech deficits in several subjects who later were found to have lesions in this area

Charles Darwin

evolution by natural selection which contributed to neuroscience

behavior is a trait that evolves just as physical traits do

animals are products of their evolutionary history, visible through shared features

the diversity of animal forms is created from a common set of animal cells/tissues

3 Rs of Animal Use in Science

reduction in the number of animals used

refinement of experimental methods to make them less invasive

replacement of animals with other investigative methods

Neurons

nervous system cells

detect environmental stimuli, process information, communicate changes to other neurons, and command body response

Glia

nervous system cells

insulate, support, and nourish neurons

maintain extracellular (solutes), provide physical support, perform immune and chemical scavenging

Histology

microscopic study of the cellular organization of tissue

requires several techniques: chemical preservation of tissue, chemical clearing and selective staining (using dyes) of preserved tissue, sectioning of stained tissue into very thin slices, and microscopic examination/description/imaging of tissue slices

Nissl Stain

stain for rough endoplasmic reticulum used to facilitate study of nervous system cytoarchitecture

Golgi Stain

stain developed by Camillo Golgi that reveals soma as well as neurites

used by Golgi and Santiago Ramón y Cajal for the first careful examinations of how neurons receive information and communicate with other neurons

Santiago Ramón y Cajal

use of an improved Golgi stain to demonstrate that neurons are not physically interconnected

demonstrated that the neurites of neighboring neurons may be extremely close to each other but do not physically join

The Neuron Doctrine

neurons communicate by contact not continuity

Neuron Specialized Features

can be long

cell extensions (neurites), principally axons and dendrites

high-densities of membrane-bound ion channels

specific suites of receptors

specialized cellular machinery for neurotransmitter synthesis/packaging/delivery

do not touch

communicate using neurotransmitters

Soma

cell body that is typical of a eukaryotic cell

includes cytosol and organelles

Cytosol

water-based intracellular fluid

Organelles

membrane-enclosed structures within the soma

Cytoskeleton

internal scaffolding of protein filaments

provides support, transmission of mechanical signals from outside of the cell to inside, and structured pathways for the internal movement of vesicles

very adjustable

three principle components: microtubules, microfilaments, neurofilaments

Neuronal Membrane

about 5 nm thick phospholipid bilayer that encloses the cytoplasm

central to neuronal function

protein concentration and types varied across it and among neuronal types

Neurites

extensions of the neural membrane into processes of variable length/width/branching

form and number is highly variable depending upon neuron functional role

includes axons and dendrites

Dendrites

function as antennae to detect signals external to the neuron

may be single in form but more typically are numerous/branching forming a tree

possess specialized receptors for signal receipt

Dendritic Spines

often are focal points of input to a neuron and their number/density may be determinant of overall capability

number and density are highly plastic and sensitive to early rearing conditions

Axons

exist to conduct signals from a neuron to its target

membrane is specialized for the conduction of electrical impulses

have several specialized regions

Axon Hillock

region near soma

typically the most sensitive region

serves as a trigger zone for the beginning of output signal relay

Axon Proper

middle region

designed to reliably relay an electrical signal down the length of the axon

Axon Terminal(s)

end region

specialized for the delivery of neurotransmitter signal to target cells

no microtubules, many synaptic vesicles containing neurotransmitters, abundant membrane proteins, and large number of mitochondria

Axoplasmic/Axonal Transport

highly energetically-consumptive physical translocation of vesicles via motor proteins conducted along the cytoskeleton

Anterograde Transport

soma to terminal

Retrograde Transport

terminal to soma

often used for feedback signals

Synapse

the site where neural signals pass from a pre-synaptic neuron to its target, a post-synaptic cell

Synaptic Transmission

the fundamental manner by which neurons communicate to each other and with target cells

dysfunction can lead to neural and mental disorders

Ways to Classify Neurons

neurite number

dendritic or somatic morphology

cell body location within the nervous system

functional connectivity within the CNS

axonal length

neurotransmitter used

physiological effect

metabolic or staining characteristics

Astrocytes

most important and numerous glia in the brain

fill spaces between neurons, provide physical support, influence neurite growth, and regulate chemical content of extracellular space

Myelinating Glia

physically wrap around neuronal axons

oligodendroglia (in the CNS) and Schwann cells (in the PNS)

protects axons from damage or interference

makes axonal propagation of signals faster and more reliable via insulation against ion loss

give white matter its physical appearance

Nodes of Ranvier

region where axonal membrane is exposed between adjacent glial cells

Ependymal Cells

epithelia-like cells that line the ventricles of the brain, produce cerebrospinal fluid (CSF), and serve as sites of neural generation

Microglia

perform immune functions within nervous tissue

engulf and destroy pathogens and damaged cells

Blood-Brain Barrier

formed by astrocytes surrounding neural capillaries

provides an additional barrier for the movement of chemicals from circulation to the ECF of the nervous system to protect nervous tissue from chemical damage

Spheres of Hydration

clouds of water molecules surrounding a dissolved ion or molecule, oriented so that their polarities oppose

Amphipathic

contains polar and nonpolar regions

Peptide Bonds

join amino acids to create peptides

Passive Transporters

require no cellular energy to operate

Active Transporter

require cellular energy to operate

Primary Active Transporters

powered by ATP

Secondary Active Transporters

powered by ion concentrations gradients

Channel Proteins

serve as a tunnel for ion travel across/through the membrane

allow the rapid diffusion of ions across the cell membrane

multiple membrane-spanning domains with both polar and nonpolar R groups and a specific pore size

if gated, may be triggered to open or close by one of a variety of signals

Voltage-Gated Channels

change their state when the membrane voltage reaches a particular threshold

Ligand-Gated Channels

open/close when their associated receptor binds to a specific ligand

Cation

positively-charged ion

Anion

negatively-charged ion

Transport Proteins

span the phospholipid bilayer

most often for the transport of ions

exhibit ion specificity and rapidity

can create and maintain ion gradients

can transport one or more ions

may be unidirectional or bidirectional

Simple Diffusion

no cellular energy required

through channel proteins or the membrane

movement motivated by concentration or electrical gradients

Electrochemical Gradient

the passive movement of ions across a membrane is due to the combination of their concentration and electrical gradients

Membrane Potential

the electrical potential across a membrane created by a separation of charge

voltage across a neuronal membrane at any moment

Ohm’s Law

the current is equal to the conductance times the magnitude of the voltage difference

expect greater amounts of current when permeability is high and when driving force is great

V = IR, I = gV

Equilibrium Potential

theoretical construct which identifies what would be the resting membrane potential if the electrical and concentrations gradients of any one ion were balanced

represents the electrical potential difference that exactly balances an ion’s concentration gradient

would yield no net movement of ions

Nerst Equation

used to calculate ion equilibrium potentials

Sodium-Potassium Pump

active transporters responsible for sodium and potassium concentrations

enzyme that breaks down ATP when sodium is present

three sodium out, two potassium in

all cells have them and neurons have many

Calcium Active Transporters

actively pump calcium out of the ICF to the ECF

calcium is a “go” signal in cells

Goldman Equation

extension of the Nerst equation to consider multiple ions and their individual permeabilities

suggests that these parameters are accurate descriptors of the conditions in/around a neuron cell membrane at rest

Potassium Channels

large diversity

number of neural conditions and medications based upon these channels and their (dys)function, including epilepsy because of the importance of this molecule to the resting condition of the cell

Action Potential

conveys information over long distances across the neuronal membrane

only generated if an input signal of sufficient magnitude is reached

rapid reversal of neuronal membrane charge relative to extracellular space

uniform size and all or nothing

information encoded in frequency and temporal pattern

Rising Phase

membrane potential changes from resting value to +30 mV

depolarization

occurs when sodium channels in the membrane suddenly and synchronously open allowing rapid diffusion of sodium ions into the neuron

Falling Phase

membrane potential returns to a value less than original

repolarization

sodium channels close and potassium channels open allowing rapid diffusion of potassium out of the membrane

Graded Potentials

generated in response to an incoming stimulus and exists initially as a local change in membrane potential at the site of stimulus receipt

propagates across the surface of the neuron and gradually fades in size as it travels along the neuronal surface

small/weak ones will not cause an action potential to be triggered but large enough ones will

Threshold Potential

potential at which an action potential will be triggered (> -55 mV)

easily reached at the axon hillock

Spike-Initiation Zone

portion of the neuronal membrane that is most sensitive to depolarization

sensory nerve endings on sensory neurons and axon hillock on many neurons of CNS

How to Evaluate Action Potentials

ion channels involved

physical states/performance

conductance exhibited

membrane potential

type and direction of currents that occur

Absolute Refractory Period

the neuron cannot generate another action potential for 1-2 ms

sodium channels are reset and the sodium-potassium pump restores gradient during this time

Hodgekin and Huxley

experiments using a voltage clamp revealed much of what we know about action potentials

demonstrated that action potentials were due to sodium and potassium conductance and that the opening of sodium (immediately) and potassium (delayed) channels is triggered by the change in membrane potential

sodium channels enter an inactive state and must be reset

Patch-Clamp

allows examination of of the channels and currents that exist in a tiny section of the neuronal cell membrane

opportunity to study individual channels

used to verify voltage-gated sodium channels

Relative Refractory Period

a subset of sodium channels have been reset but the neuron is able to respond only to the very strongest of stimuli

Tetrodotoxin (TTX)

toxin from puffer fish that clogs sodium-permeable pore

Batrachotoxin

toxin from poison dart frogs that blocks inactivation so channels remain open

Continuous Conduction

depolarize adjoining membrane to threshold potential to regenerate the potential

potential at location A depolarizes location B which depolarizes location C and so on

allows for transmission over long distances

Orthodromic Conduction

action potential travels in one direction down the axon to the axon terminal

normal

Antidromic Conduction

backward propagation

experimental

can be triggered using current injection into an axon

Saltatory Conduction

from node to node and jumping

sodium channels concentrated at nodes for regeneration

faster than continuous conduction

Gap Junctions

a form of junction between many types of cells that allows direct exchange of cytoplasmic material

are part of electrical synapses

useful for keeping adjoining cells synchronized in their states and activity

Electrical Synapses

pre- and post-synaptic cell membranes physically connect to one another and communicate directly via ion flow

bidirectional and extremely fast

Synaptic Integration

when connexon number is few

simple form of computation common in CNS

no individual synapse at a target neuron is powerful enough to trigger an action potential but the effects of multiple inputs combine into a singular cellular response

Chemical Synapses

use inter-cellular chemical signals between the pre- and post-synaptic cells

the majority of synapses in the animal nervous system

separated by a gap

Axodendritic

axon to dendrite synapse

Axosomatic

axon to cell body synapse