NERVOUS SYSTEM (part 1) Neurons and Electrophysiology

Introduction to Neurons

Neuron :: the electrically excitable cells of the nervous system.

Most types of neurons has three parts; the neuron cell body, dendrites, single axon.

Neuronal Structure

Neuron cell body :: performs the typical functions of any cell, such as protein synthesis and packaging of proteins into vesicles.
Axon hillock :: a single axon arising from a cone-shaped area of the neuron cell body.
Initial segment :: The axon hillock transitions to this as it narrows and is the actual beginning of the axon.
Trigger zone :: This is the combination of the axon hillock and the initial segment where action potentials are generated.
Synapse :: Point of contact between the axon ending and its effector.
Synaptic vesicles :: They store the signal molecules produced by the neuron.
Neurotransmitters :: these signal molecules control the effectors.
Dendrites :: are extensions of the cell body and receive information from other neurons or the environment portion of the neuron.
Dendritic spines :: they are small extensions on dendrite surfaces where axons of other neurons form connections with the dendrites.
When stimulated, dendrites generate small electric currents, which are conducted toward the neuron cell body.

Functional Classification of Neurons

Sensory neurons (afferent neurons) :: conduct action potentials toward the CNS.
Motor neurons (efferent neurons) :: conduct action potentials away from the CNS toward muscles or glands.
Interneurons :: conduct action potentials within the CNS from one neuron to another.

Myelination Plays a Role in Signal Conduction

Myelinated Axons :: Schwann cells in the PNS or oligodendrocyte extensions in the CNS repeatedly wrap around a segment of an axon to form a series of tightly wrapped membranes rich in phospholipids, with little cytoplasm sandwiched between the membrane layers.
Nodes of Ranvier :: These are gaps in the myelin sheath. This is an area of the myelin sheath that is much thinner and about 2-3 um in length.
Unmyelinated Axons :: The axons rest in invaginations of the Schwann cells or oligodendrocytes. They are not devoid of myelin.
Saltatory conduction :: describes the way an electrical impulse skips from node to node down the full length of an axon, speeding the arrival of the impulse at the nerve terminal.
- This takes place in myelinated axons.
- It is the fasted method of transmission of the action potential.
Diffusion Tensor Imaging (DTI) :: Visualizes white matter connectivity in the brain and it also measures movement of water at microstructural level.

Glial Cells

Glial Cells :: Important in the nervous system and a major support cell for neurons.

Electrophysiology

Definition of terms

Action potential :: electrical signals produced by the nervous system.
Membrane potential :: a measure of the electrical properties of the cell membrane. Membrane potential has two major characteristics :: Ionic concentration differences across the plasma membrane, and Permeability characteristics of the plasma membrane.
Diffusion :: the characteristics of electrically excitable cells and the generation of action potentials are due to this principle.

Permeability of Membranes

Sodium-potassium pumps :: All along the neuron axon, they actively pump K+ against its concentration gradient into the cell, while at the same time, they pump Na+ against its concentration gradient out of the cell.
Negatively charged proteins :: are regularly synthesized inside the cell; because they are large and relatively insoluble, they cannot easily diffuse across the plasma membrane and stay inside the cell.
Negatively charged Cl- :: this exits the cell due to it being repelled by the negatively charged proteins and other negatively charged ions inside the cell, causing a higher concentration of Cl- outside than inside.

Ion Channels

Ion channels :: Ions must pass through the plasma membrane through these channels.
Leak ion channels or Non-gated ion channels :: are always open and are responsible for the permeability of the plasma membrane to ions when the plasma membrane is unstimulated or at rest.
Gated ion channels :: are closed until opened by specific signals which can change the permeability of the plasma membrane.
Ligand-gated ion channels :: stimulated to open by the binding of a specific molecule to the receptor site of the ion channel.
Voltage-gated ion channels :: open and close in response to a specific, small voltage change across the plasma membrane.
Other gated ion channels :: respond to stimuli other than ligands or voltage changes; they are present in specialized electrically excitable tissues.

Establishing the Resting Membrane Potential

Potential difference :: it is the electrical charge difference across the plasma membrane.
Resting membrane potential :: it is the potential difference in an unstimulated, or resting cell.
K+ is higher inside the cell than outside while Na+ is higher outside the cell than inside.
Due to more K+ leak channels, the plasma membrane is 50-100 times more permeable to K+ than to other positively charged ions. The potassium ions leak out of the cell faster than positive sodium ions enter the cell and therefore create a slightly negative charge inside of the cell.
Large intracellular, negatively charged molecules such as proteins are trapped inside the cell because the cell is impermeable to them.
The slight negative charge inside the cell attracts positively charged K+ back into the cell. When the negative charge inside the cell is great enough to prevent additional K+ from diffusing out, an equilibrium is established.
Difference in potential :: the charge difference across the plasma membrane at equilibrium which is measured in millivolts (mV).
Equilibrium :: very little movement of K+ or other ions takes place across the plasma membrane.
Nernst Equation :: E ion = 58mv/z (log(extracellular/intracellular)), where z = ion valence (charge).
- Constant is sometimes 61.5mv instead of 58mv depending on the textbook.
Depolarization :: is the process or act by which polarity is eliminated.
- Most cells are negatively charged relative to their surroundings. This negative charge of the cell shifts to a positive through the process of depolarization.
- Depolarization only occurs for a brief moment of time.
- No net difference (“De”-polarize)
- Outside more positive, Inside more negative → Outside remains positive, Inside becomes more positive.
- In depolarization, resting membrane potential moves towards zero.
Hyperpolarization :: is a process or act resulting in the membrane potential of a cell more negative than it typically is.
- Too much difference (“Hyper”-polarize)
- Outside more positive, Inside more negative → Outside remains more positive, Inside becomes even more negative.
- In hyperpolarization, resting membrane potential moves farther away from zero.

Graded Potential

Graded potential :: is a relatively small change in the membrane potential localized to one area of the plasma membrane. They are called graded potentials because they vary in size depending on the strength of the stimulus.
Summation :: combination of graded potentials, which, if sufficiently large, will result in action potential.
Temporal Summation :: occurs when a series of subthreshold EPSPs in one excitatory fiber produce an action potential in the postsynaptic cell. This occurs because the EPSPs are superimposed on each other temporally before the local region of membrane has completely returned to its resting state.
Spatial Summation :: occurs when stimuli are applied at the same time, but in different areas, with a cumulative effect upon membrane potential. Spatial Summation uses multiple synapses acting simultaneously.
Threshold :: the membrane potential at which an action potential is generated. An action potential is generated when voltage-gated Na+ channels open.

Action Potential

Action potential :: the means by which neurons communicate with their effectors. Action potential results from summation of graded potential.
All-or-none principle :: if a stimulus produces a depolarizing graded potential that is large enough to reach threshold, all the permeability changes responsible for an action potential proceed without stopping and are constant in magnitude.
Refractory period :: the time period where an area is less sensitive to further stimulation.
Absolute refractory period :: the first part of the refractory period, during which complete insensitivity exists to another stimulus no matter how strong.
Relative refractory period :: the time period where a stronger-than-threshold stimulus can produce an action potential.

Synapses

Electrical synapses :: occur between cells connected by gap junctions.
Gap junctions :: a 2 nm gap between adjacent cell membranes where cytoplasm is shared through tunnel-like protein structures called connexons.
Chemical synapse :: occurs where a chemical messenger , called a neurotransmitter, is used to communicate a message to an effector. The parts of a chemical synapse are the presynaptic terminal, the synaptic cleft, and the postsynaptic membrane.
Presynaptic terminal :: consists of the end of an axon of the presynaptic cell.
Synaptic cleft :: The space separating the axon ending and the cell with which it synapses.
Postsynaptic membrane :: the membrane of the postsynaptic cell associated with the presynaptic terminal. Postsynaptic cells are typically other neurons, muscle cells, or gland cells.

Process of Communication at the Synapse

In most synapses of the body, communication between the neuron and its target cells occur through chemical signals.
Neurotransmitters :: act as the chemical signals and are stored in synaptic vesicles in the presynaptic terminal.

When an action potential reaches the presynaptic terminal, voltage-gated Ca2+ channels open and Ca2+ moves into the cell.
The influx of Ca2+ release neurotransmitters by exocytosis from the presynaptic terminal.
Neurotransmitters diffuse across the synaptic cleft toward the postsynaptic membrane.
Neurotransmitters bind to specific receptor molecules of the postsynaptic membrane.

Neurotransmitters

Neurotransmitters can be classified on the basis of their chemical structure, their effect on the postsynaptic membrane, and their mechanism of action at their target.
Ionotropic receptor :: also known as ligand-gated receptors.
Metabotropic receptor :: also known as G-protein coupled receptors, it is a type of membrane receptor that initiates a number of metabolic steps to modulate cell activity.
Acetylcholine (ACh) :: a neurotransmitter released from CNS synapses which has an excitatory effect, ANS synapses which has an inhibitory effect, and a neuromuscular junction which has an excitatory effect; its mechanism of action is ionotropic.
Serotonin :: a neurotransmitter released from CNS synapses which mostly has inhibitory effects; its mechanism of action is metabotropic and ionotropic.
Dopamine :: a neurotransmitter released from selected CNS synapses and some ANS synapses which has excitatory or inhibitory effects; its mechanism of action is metabotropic.
Norepinephrine :: a neurotransmitter released from selected CNS synapses and some ANS synapses on most sympathetic targets which has excitatory effects; its mechanism of action is metabotropic.

Clinical Modulation of Selected Neurotransmitters

Depression and Anxiety :: Serotonin is important for emotional states such as these.
Epilepsy :: Characterized by excessive neuron function, Lock of GABA induces convulsions.
ADHD :: Characterized by an inability to focus. It is often treated with drugs that increase the level of excitatory neurotransmitters, such as norepinephrine in the synaptic clefts.
Parkinson Disease :: Loss of muscular contraction control. Characterized by tremors and decreased voluntary motor control. It is treated with the drug L-Dopa, which increases the production of dopamine in the presynaptic terminals of remaining neurons.
Stroke :: damage in the brain that results in a disruption in or lock of blood flow to the brain.