Nervous System Divisions and Structures

Divisions of Nervous System

• There are two broad divisions: the central nervous system (CNS) and the peripheral nervous system (PNS).
• The CNS includes the brain and spinal cord.
• The PNS encompasses everything else: nerves and ganglia.
• The nervous system functions in communication and coordination.

Structures of Nervous System

• The neuron is a nervous system cell.
• Neurons contain components such as the soma, axon, and dendrites.
• Neurons are supported by neuroglia, also known as glial cells.
• Functions of neurons include myelination and insulation.

CNS Components

• Gray matter consists of soma and dendrites which process information, and has little myelin.
• White matter consists of axons, transmits information and has myelin.

PNS Components

• A nerve is a bundle of axons that transmits information.
• A ganglion is a cluster of soma, acts as relay stations.

Sensory Pathway

• Sensory receptors are found throughout the body and consist of exteroceptors and interceptors.
• Sensory receptors respond to stimuli by producing a change in their membrane voltage, which is called graded potential.
• If the stimulus is strong enough, a large electrical signal called an action potential will travel along the axon.
• Signals travel between neurons via neurotransmitters, eventually reaching the thalamus.
• The thalamus relays the sensory information to the appropriate destination in the cerebral cortex.
• This process results in conscious perception of the stimulus.

Clinical Connection: Local Anesthesia

• Local anesthetics work by blocking the transmission of pain signals along specific pathways and are typically injected.
• Lidocaine is an example of a local anesthetic used for oral surgery.
• A spinal block involves injecting anesthetic into the cerebrospinal fluid (CSF) around the spinal cord.
• An epidural involves injecting anesthetic into the epidural space.

Clinical Connections: General Anesthesia

• General anesthesia involves the administration of drugs that place the brain into a reversible, drug-induced coma.
• There are three phases of general anesthesia: induction, maintenance, and emergence.
• Induction is the process of producing a state of sedation.
• Maintenance involves monitoring physiological parameters such as heart rate and blood pressure to maintain sedation and non-response to pain signals.
• Emergence is usually a passive process as the drugs are reduced, and physiology is monitored throughout.

Motor Pathways

• Motor signals typically begin in the cerebral cortex, specifically in the precentral gyrus of the frontal cortex.
• Action potentials travel along neurons and pass the signal across synapses by neurotransmitters.
• Neurotransmitters are released to stimulate the effector, such as skeletal muscle.
• Motor pathways are descending pathways.
• An example of a major motor pathway is the corticospinal tract.
• The upper motor neuron runs from the cortex to the spinal cord.
• The lower motor neuron runs from the spinal cord to the effector (muscle).

Autonomic Nervous System (ANS)

• The ANS controls involuntary responses to regulate homeostasis.
• Nerve pathways are composed of two neurons: preganglionic and postganglionic neurons.
• The sympathetic division functions for fight or flight responses.
• The parasympathetic division functions for rest and digest responses.

Ions and the Plasma Membrane

• An ion is an atom or molecule with a net electric charge.
• The plasma membrane of a cell is selectively permeable.
• Ions cannot pass through the membrane without assistance and transmembrane proteins allow this movement.
• The sodium-potassium pump moves Na+ out of the cell and K+ into the cell, creating a concentration gradient and uses active transport and energy (ATP).
• Ion channels are proteins that allow specific ions to cross the membrane and can be gated, meaning they are only opened by specific events.
• A ligand-gated channel opens when a signaling molecule (ligand) binds to the channel.
• A mechanically-gated channel opens because of physical distortion of the plasma membrane.
• A voltage-gated channel opens in response to a specific voltage.
• A leakage channel is randomly gated, opening and closing at random.

Resting Membrane Potential

• The -70mV charge stays steady, and is the resting membrane potential (RMP).
• It is due to the activity of leakage channels, where Na+ leaks into the cell and K+ leaks out.
• The sodium-potassium pump returns them to their original locations

ANS: Sympathetic Division Structure

• The thoracolumbar division has preganglionic neurons starting in the thoracic and lumbar regions of the spinal cord.
• It has short preganglionic and long postganglionic neurons.
• The primary postganglionic neurotransmitter is norepinephrine (NE).

ANS: Parasympathetic Division Structure

• The craniosacral division preganglionic neurons begin as cranial nerves and in the sacral region of the spinal cord.
• It has long preganglionic and short postganglionic neurons.
• The primary postganglionic neurotransmitter is Acetylcholine (ACh).

Graded Potentials

• Graded potentials are local changes to the membrane potential.
• They usually occur in the dendrites of a neuron.
• They can be positive (depolarizing) or negative (hyperpolarizing).
• Graded potentials are caused by the opening of ion channels.
• If the graded potential raises the membrane potential to threshold (usually -55mV), this will produce an action potential.

Action Potentials

• An action potential is a rapid change in electrical potential across a neuron's membrane and functions as a nerve signal to transmit information along an axon.
• Key properties include all or nothing (either occurs fully or not at all), threshold (will not happen unless depolarization reaches threshold of -55mV.
• is nondecremental which means it stays the same strength along the length of the axon, and refactory period, where after an action, it is impossible to start another action potential.

Action Potential Steps

1. Stimuli open Na+ channels in the neuron and Na+ enters, and positively-charged Na+ raises membrane potential from -70mV as depolarization occurs.
2. Voltage-gated Na+ channels open at -55mV threshold which causes fast depolarization
3. Na continues to flow in until membrane potential reaches +30mV, and inactivation gates close preventing more Na+ from entering the neuron.
4. K+ channels have finally opened, and K+ moves down gradient and leaves the cell which returns the membrane potential to a negative value or repolarization.
5. The membrane potential briefly overshoots the -70mV resting membrane potential (hyperpolarization)
6. The entire up or down shift in electrical potential is called an action potential.

Communication With Other Neurons

• A synapse is a junction where a neuron meets another cell (neuron, muscle, etc.).
• The synaptic cleft is the separating space between neurons.
• Neurotransmitters travel across the cleft, continuing the signal.
• Effects of the signal are related to the type of receptor.
• The ionotropic receptor has a direct effect when a neurotransmitter binds to it
• The metabotropic receptor has an indirect effect, causing signaling changes in the cell when a neurotransmitter binds to it.

Key Classes of Neurotransmitters

• The cholinergic system uses neurotransmitter acetylcholine (ACh).
• There are two types of receptors: nicotinic and muscarinic receptors.
• Amino acids, such as GABA is another class.
• Biogenic amines, which are formed by removing the carboxyl group from an amino acid and and example is norepinephrine.
• Finally, neuropeptides examples include Beta-endorphin.

Direct vs. Indirect Action of Neurotransmitters

• In direct action, a neurotransmitter binds to an ionotropic receptor, and the channel opens.
• In indirect action, a neurotransmitter released into synaptic cleft, neurotransmitter binds to metabotropic receptor activating G protein which binds to effector protein, which activates enzymes and open channels

Postsynaptic Potentials

• Neurotransmitters can cause the creation of a postsynaptic potential in the receiving neuron.
• The two types are: excitatory postsynaptic potential (EPSP) and inhibitory postsynaptic potential (IPSP).
• EPSP moves the membrane potential toward threshold and the receiving neuron is MORE likely to create an action potential
• IPSP moves the membrane potential away from threshold and the receiving neuron is LESS likely to create an action potential.

Types of Muscle Tissue

• There are three types of muscle tissue: Skeletal, Cardiac and Smooth.
• Skeletal muscle is a voluntary and connected to bones.
• Cardiac muscle is involuntary, only found in the heart, and is strained.
• Smooth muscle is involuntary, found in organs, and is not strained.

Myofibers and Muscles

• The myofiber is the cell of skeletal muscle tissue.
• It's voluntary, striated muscle.
• Myofibers are bundled with connective tissue into fascicles.
• Multiple fascicles form muscles.
• Often connected to bones by tendons.

The Triad

• Includes: T-tubule, Sarcoplasmic reticulum (SR), and Terminal cisternae
• T-tubule: transverse "tunnels" that cross the myofiber.
• Sarcoplasmic reticulum (SR): Specialized endoplasmic reticulum that stores calcium ions (Ca2+).
• Terminal cisternae: enlarged ends of the SR.
• Triad is two terminal cisternae on either side of a T-tubule.

Key Muscle Proteins

• The contractile proteins facilitate muscle contraction with myosin: forms thick filaments and actin: forms thin filaments.
• The regulatory proteins determine timing of muscle contraction with tropomyosin which shields myosin-actin binding sites , and troponin which binds to Ca2+, moves tropomyosin from binding sites.
• Stability and organization of the sarcomere is done using structural proteins with titin that forms elastic filaments which act as a molecular "spring"
• Dystrophin: transfers force from sarcomere to connective tissues.

Sarcomere

• The sarcomere is the contractile unit of skeletal muscle.
• Formed by overlapping thick and thin filaments and the structures are: I band, A band, Z disc, H band, M line

Motor Units

• Motor unit: a somatic motor neuron and the muscle fibers it innervates.
• Small motor units (3-5) have few muscle fibers per neuron and allow fine control.
• Large motor units (100-1000) have many muscle fibers per neuron and provides strength for large (gross) movements.

Excitation-Contraction Coupling 1 and 2

• Muscle contraction starts with electrical excitation of the myofiber:
• An action potential arrives at the NMJ.
• Action potential triggers opening of voltage-gated Ca2+ channels in the synaptic end bulb.
• Influx of Ca2+ causes release of ACh from synaptic vesicles (exocytosis).
• ACh diffuses into the synaptic cleft and binds to ACh receptors on the motor end plate of the myofiber.
• Channels open in the ACh receptors, allowing inflow of Na+, depolarizing

Excitation-Contraction Coupling 3

• Nearby voltage-gated Na+ channels open, more Na+ enters the myofiber, passing the depolarization along the entire myofiber.
• T-tubules carry the action potential into the myofiber interior, triggering the release of Ca2+ from the sarcoplasmic reticulum.

Muscle Contraction 1

1. Ca2+ ions bind to troponin and cause it to change shape.
2. This moves the tropomyosin off the myosin-actin binding sites.
3. Myosin heads bind to actin (form a cross-bridge)

Muscle Contraction 3

6. ATP provides energy to "load" myosin heads into a high-energy state.

7. Energy is released by the hydrolysis of ATP into ADP + Pi.

8. Another cross-bridge is formed, ADP + Pi is released, and the myosin/actin slide over each other.

Muscle Contraction 2

4. Myosin heads snap back to their original position, pulling actin along and shortening the sarcomere which is called the sliding filament theory.
5. ATP binds to the myosin heads, removing them from actin.

Muscle Relaxation

1. Signal from the motor neuron ends (stopping release of ACh).
2. Remaining ACh degraded by the enzyme acetylcholinesterase (AChE).
3. Sarcolemma and T-tubules repolarize which goes back to RMP.
4. Ca2+ ions are pumped back into the SR.
5. Tropomyosin slides back in place, shielding the myosin-actin binding sites.
6. Sarcomere recoils back to starting point, aided by elastic filaments (titin).

Length-Tension Relationship

• Skeletal muscle contraction is strongest when the sarcomere is at an intermediate length.
• Contraction requires overlap of myosin and actin
• A fully contracted muscle does not allow further sliding of the filaments

Clinical Connection: Botulism

• Botulinum toxins are released by the bacteria Clostridium botulinum and toxins block release of ACh from synaptic vesicles.
• One source is improperly canned foods.
• Can cause death by paralyzing respiratory muscles.
• Botox is a pharmaceutical product produced by the same bacteria that is purified and diluted for uses such as cosmetic to smooth wrinkles by relaxing facial muscles.
• It's also used for treating vocal cord spasms, reducing chronic back pain caused by muscle spasms, and reducing excessive sweating (hyperhidrosis).

Skeletal Muscle Metabolism 1

• Contraction requires a steady supply of ATP and uses three mechanisms to provide this ATP: Creatine phosphate.
• Creatine phosphate "recharges" ADP by donating phosphate and involves immediate energy for 0–10 sec of activity.

Skeletal Muscle Metabolism 2

7. Glycolysis uses an anaerobic process that, breaks glucose into 2 ATP and pyruvate
8. If oxygen not available, pyruvate converted to lactic acid
9. Short-term energy is used for 10-40 seconds.
10. Aerobic respiration
11. In presence of O2, mitochondria process pyruvate, producing ~36 ATP per glucose
12. Long-term energy 40+ seconds

Sources of Energy and Oxygen Debt

• The sources of energy include blood glucose, stored glycogen, and aerobic respiration involving pyruvate and fatty acids.
• Oxygen debt is the oxygen needed to compensate for anaerobic ATP production after intense exercise.
• This helps replenish the ATP and creatine phosphate stores, helps process lactic acid and is observed as increased breathing rate after exercise.
• Skeletal muscle is a types of muscle fibers.

Types of Muscle Fibers

• Slow oxidative (SO) fibers (Type I) (Red fibers) are "Slow twitch" fibers
• They are for aerobic respiration:extensive blood supply, myoglobin, lots of mitochondria and examples:posture, stability muscles, endurance exercise
• Fast glycolytic (FG) fibers (Type 11b) (white fibers) are "Fast twitch"fibers which primarily use anerobic glycolysis: lots of glycogen, less mitochondria and myoglobin. Examples: quick forceful exercise, resistance exercise
• Fast oxidative (FO) fibers (Type IIO) are "Intermediate" fibers and used for "everyday" movement such as walking.

Smooth Muscle Contraction

• Spindle-shaped cells, much shorter and smaller than skeletal muscle fibers. Not striated – different arrangement of actin and myosin
• Regulatory protein calmodulin responsible for initiation of sliding filaments
• Most of the Ca2+ ions come from the extracellular space during contraction rather than the SR

Development and Repair of Other Muscles

• Smooth muscle can regenerate by mitosis.
• Cardiac muscle cannot regenerate, and damage is replaced by fibrosis.

Development and Repair of Skeletal Muscle

• Some embryonic mesoderm develops into myoblasts which are the muscle-forming stem cells. Many myoblasts fuse to form the long myofibers of skeletal muscle
• This explains the multiple nuclei of a mature myofiber.
• Myosatellite cells are stem cells found around mature myofibers that can repair minor damage to myofibers.
• Major damage results in the formation of scar tissue (fibrosis)