Cell and Molecular Neuro Flashcards
Neurophysiology
Branch of physiology abd neuroscience concerned with function of the nervous system.
Significance
As chiropractors we affect the nervous system with each adjustment
Where in the spine are sensory receptors?
Everywhere including the outer 1/3 of the vertebral disc.
Injured state resulting in sensitization of nociceptors
Can result from major trauma or repetitive microtrauma. Results in sympathetic hypersensitivity
During an adjustment what happens to mechanic receptors?
Stimulate Joint mechanoreceptors, which can potentially decrease nociceptive activation
In other cases may contribute to sensitized state
Classes of neurons
Multipolar
Psuedouniploar
Bipolar
Multipolar Neuron
has a single axon and contains multiple dendrites extending from the soma
Psuedounipolar/unipolar
Contains a single process extending from the soma that can branch to form dendrites and axon terminals
Bipolar neuron
Contains two processes, One axon and one dendrite extending from the soma.
CNS Terminology
NUCLEI - refers to neuron cell bodies that are morphologically distinct
TRACTS - refer to multiple axonal processes that are morphologically distinct in a bundle
PNS terminology
GANGLIA - refers to multiple neuron cell bodies
NERVES - are multiple axons in a distinct bundle
Reticular Theory
Outdated Theory by Camillo Golgi
Neurons are connected to neighboring neurons through protoplasmic links
Neurons linked together forms continuous nerve cell network or “reticulum”
Information may flow in any direction within the network
(Main Ideas of) Contact Theory
Argued against Reticular Theory (By Santiago Ramon y Cajal)
Neurons are distinct cells
Neurons communicate with each other at distinct points of contact
5 principles of Contact Theory
1) Neuron is the elementary structural and signaling unit of the nervous system
2) Information is recieved at a receptive point of a neuron and travels in a unilateral direction along the axon to the terminal LAW OF DYNAMIC POLARIZATION (specialized areas for receiving and sending)
3) The axon terminal of one neuron is in close proximity with the receptive region of another neuron at a specialized junction called a synapse
4) An individual neuron will only communicate with synaptic contacts on specific portions of a neuron. Connection between neurons are not random, neuronal circuits pass information through specific pathways. Concept is CONNECTION SPECIFICITY
5) Connections between neurons can be modified by experience, either through strengthening or weakening of synapses. Makes brain function more efficient. SYNAPTIC/NEURAL PLASTICITY
Electrophysiology
Can provide a detailed picture of the events taking place at the individual cell level.
Digital Cathode Ray Oscilloscope
A lab instrument that provides accurate time and amplitude measurements of voltage signals over a wide range of frequencies
CRO Macroelectrodes
Measure the activity of a population of cells
CRO Micro-electrodes
Can be placed in or near a single cell to measure that cells electrical activity
Population (Global) recording
Utilizes macro-electrodes
Measures voltage
EEG (for the cortex)
EMG (muscles)
ERP (specific sensory pathway) activity of the brain in response to a stimulus
Whole nerve (Peripheral nerves)
Excellent temporal resolution, poor spatial resolution
Clinical assessment (provides us with knowledge of whether or not there is a problem)
Single Cell Recording
Utilizes Micro-electrodes Measures Ion current and voltage Resting Membrane Potential IPSP, EPSP AP Intracellular (in Vito, in vitro) Extracellular (in vivo) Patch clamp (in vitro)
Experimental method
Neural connection properties
Electrical Unique to excitable cells Very fast Only the plasma membrane is involved ATP-dependent Signaling is directly and indirectly coupled to all cellular biochemical process by ion channels and numerous signal transduction pathways (STPs)
Membrane voltages
Graded (EPSPs, IPSPs) or All or None (AP)
Graded potentials occur at dendrites and the soma
AP are initiated at a region adjacent to the axon hillock and travel along the axon to the terminal button
Both rely on activity of ion channels located throughout the plasma membrane
ERP
Measuring activity in a sensory pathway
Visual (Flash, Pattern)
Auditory (Click, Tone)
Sensory (Light touch, Pressure)
Three techniques of Single Unit Electrophysiology
Extracellular: Voltage measurement taken outside of the cell, which records all-or-none action potentials
Intracellular: Voltage measurement taken inside of the cell which records Resting Membrane Potential, graded potentials, and APs
Patch Clamp: Records ionic current (not voltage) of either a single or a group of ion channels
Resting Membrane Potential
Allows the membrane to be in a “ready state”. All electrical activity results from a change to this potential.
-70mV (between -40 and -90 mV dependent on size)
Ionic basis of the Resting Membrane Potential
Neurons exist in an aqueous environment with + and - ions.
Ion species will attempt to achieve their own equilibriums.
The charge built up across the membrane at rest results from the differential distribution of the ion species.
More negative ions on the inside than on the outside.
Ion distribution in a neuron at rest
More Na+ and Cl- ions are found on the outside of the neuron
More K+ and negatively charged ions are found on the inside of the neuron
Homogenizing factors across the neural membrane
Random motion (concentration gradients)
Electrostatic pressure (like charges repel and opposite charges attract)
Chemical synapses
Allow for cell to cell communication via the release of chemical agents (neurotransmitters) by presynaptic neuron.
Neurotransmitter release
Released from synaptic vesicles from the Presynaptic axon terminal
Released synaptic cleft
Three types of chemical synapses
Axodendritic - most common. Synapse on dendrite of postsynaptic neuron.
Axosomatic - synapse on the soma
Axoaxonic - synapse on the axon
Properties of electrical synapse
3.5nm synaptic cleft with a 10-100 usec delay. Near instantaneous signaling.
Some synaptic plasticity but no amplification
Properties of chemical synapse
20-40nm synaptic cleft. 1-5msec delay.
Provides temporally and spatially focused transmission. Provides alterations in synaptic core goth efficiency.
Synaptic plasticity and signal amplification.
Chemical synapses divided by distance
Directed - neurotransmitter release site and reception site are in close proximity.
Non-directed - release site is at a distance from reception site.
Neuromuscular junction
Chemical synapse between extramural and intramural muscle fibers of striated and skeletal muscle.
All NMJs utilize acetylcholine (ACh)
Motor unit
One alpha neuron and all extramural muscle fibers innervated by its axon (branches at its terminal end.
Nicotinic ACh receptor
Large protein consisting of 5 subunits. Alpha subunit contains an ACh-binding receptor.
Central pore functions as a passage for Na+ ions.
CNS chemical synapses properties
Multiple transmitter ligands. Graded response consisting of EPSP and IPSP. Summation is necessary. Receptors may be ionotropic or metabotropic.
Presynaptic inhibition or facilitation.
Properties of NMJ (PNS chemical synapses)
Single transmitter ligand. End Plate Potential (depolarization only). Only excites target. Only ionotropic receptors.
How are postsynaptic potentials generated?
Binding of neurotransmitter on receptor causes the opening of ion channels and can induce depolarization or hyperpolarization.
Depolarization
Bringing membrane potential closer to threshold of excitation (EPSP)
Hyperpolariztion
Makes the membrane potential more negative. IPSP
Properties of EPSPs/IPSPs
Graded potentials with varying amplitudes. Travel passively but rapidly from site of origin. Decrease in amplitude as they travel along the axon (decremental)
Generation of AP
Sum of IPSPs and EPSPs must be sufficient to reach the threshold of excitation
-55mV to generate an AP
Generated in the region adjacent to the axon hillock
Features of an AP
Momentary reversal of membrane potential from - to +
All or none response
Directly related to the concentration of Na inside and outside the cell
Voltage gated ion channels mediate the production and conduction of APs by altering the membrane potential.
Two types of summation
Spatial - Multpile PSPs from different synapses are combined to form a a larger PSP
Temporal - Multiple PSP form the same synapse combine to form a larger PSP
Phases of an action potential
Resting state Threshold Depolarization phase Depolarization phase Undershoot Refractory Phase Absolute refractory phase Relative refractory phase Return to Resting State
Resting state
Voltage gated Na and K ion channels are closed and leak ion channels are open. Membrane potential is a RMP
Threshold
One or more excitatory potentials (EPSPs) opensomevoltage-gated Na ion channels. When the threshold is reached, more Na+ ion channels will open and an action potential is triggered.
Depolarization phase
With Na ion channels open, Na ions continue o rich into the cell, which alters the membrane potential.
K ion channels are still closed.
Repolarization phase
Voltage gated ion channels become INACTIVE while K ion channels begin to open.
K ions rush OUT OF the cell to change the membrane potential.
Undershoot
Na ions channels are closed and K ion channels are closing but slowly K ions are still leaving the cell through the remaining open channels. Making the membrane potential more negative
Refractory Period
in the wake of the AP, Na ion channels are deactivated for a brief time. Makes it difficult for the neuron to produce an AP.
Absolute Refractory Period - from initiation of AP to immediately after the peak. Cannot lead to another AP.
Relative Refractory Period - following absolute refractory period. Na channels begin to recover from inactivation. A stronger than normal stimulus is needed to elicit an action potential.
Return to Resting State
The RMP of the neuron is restored as all K+ ion channels close and the Na/K pumps work to re-establish baseline concentration of these ion channels.
Anti-Homogenizing factors across cell membrane
Neural membrane has different permeability to ions
passive property as it uses ion channels. K+ and C- can pass through the membrane. Na+ moves through with difficulty and (-) ions cannot move through at all.
Membrane bound transporters that consume energy.
Na-K pump that exchanges 3 intracellular Na+ ion for 2 extracellular K+ ions. MAJOR factor in maintaining the differential ion concentrations,
Cl- ions in the neuron
Can readily diffuse across membrane. Negative internal potential drives Cl- ion s out of the neuron. As the ions accumulate outside the cell the concentration gradient pushes them into the neuron.
Na+ ions
Has difficulty diffusing across the membrane. Tend to move into the cell due to their high extracellular pressure and negative charge of internal neuron. Na-K pump moves the Na out of he cell at the same slow rate that they enter the cell (maintains -70 mV)
K ions in the neuron
neural membrane allows K+ ions to readily diffuse. Moves out of cell due to high internal concentration. Internal negative pressure moves ions back into the cell. Na-K pump maintains charge by moving K ions into the cell at the same rate that they leave.
Two types of ion channels
Leak (non-gated) ion channels
Gated ion channels
Non-gated ion channels
open even in a resting state
selective for a single ion species
contributes to RMP
gated ion channels
closed until opened by a stimulus
can be selective for one or multiple ion species.
Necessary for graded or all or none potentials and neurosecretions. (depolarizing and hyperpolarizing effects)
Location of ion channels
Leak channels: cell body, dendrites, axon
Ligand gated channels: Cell body, dendrites
Voltage gated channels: Axon Hillock region, Axon, axon terminal