The Nervous System: Anatomy and Function

• The nervous system governs perception, experience, voluntary movement, consciousness, personality, learning, and memory.
• It also regulates respiratory rate, blood pressure, body temperature, sleep/wake cycle, and blood pH alongside the endocrine system.

Anatomical Divisions

• The central nervous system (CNS) includes the brain and spinal cord.
• The brain consists of billions of neurons and is protected by the skull.
• The spinal cord starts at the foramen magnum, extending through the vertebral foramina from the first cervical to the first or second lumbar vertebra.
• The peripheral nervous system (PNS) comprises all nerves outside the skull and vertebral column.
• Nerves are bundles of neuron axons with blood vessels and connective tissue, carrying signals to and from the CNS.
• Cranial nerves are 12 pairs connecting to or from the brain.
• Spinal nerves are 31 pairs connecting to or from the spinal cord.

Functional Divisions

• The nervous system has sensory, integrative, and motor functions.
• Sensory functions gather information via the afferent division of the PNS, divided into somatic and visceral divisions.
• The somatic sensory division transmits signals from skeletal muscles, bones, joints, skin, and special sensory organs.
• The visceral sensory division transmits signals from organs like the heart, lungs, stomach, kidneys, and bladder.
• Integrative functions analyze sensory input to determine appropriate responses.
• Motor functions are actions in response to integration, managed by the efferent division of the PNS.
• The motor division consists of motor neurons traveling from the brain and spinal cord, using cranial and spinal nerves.
• Effectors are organs that carry out the effects of the nervous system.
• The somatic motor division controls skeletal muscle voluntarily.
• The autonomic nervous system (ANS) or visceral motor division controls thoracic and abdominal viscera.
• The ANS regulates gland secretion, smooth muscle contraction, and cardiac muscle contraction involuntarily to maintain homeostasis.

Neurons

• Neurons are excitable cells sending and receiving signals via action potentials.
• Neurons include a cell body (soma), dendrites, and an axon.
• The cell body is the neuron's metabolically active region, manufacturing proteins, supported by:
  • Free ribosomes and rough endoplasmic reticulum (Nissl bodies) for protein synthesis.
  • Golgi apparatus for vesicular transport, and multiple nucleoli for ribosomal RNA production.
  • Mitochondria for energy.
• The cytoskeleton contains microtubules for structural support and chemical transportation.
• Neurofibrils, made of intermediate filaments, offer structural support within neuron processes.
• Processes, including dendrites and axons, enable neuron communication.
• Dendrites are short, branched processes that receive and transmit input to the cell body.
• Each neuron has one axon that generates and conducts action potentials.
• Distinct axon regions include:
• Axon hillock - origin from cell body.
• Axon collaterals - branches from the main axon.
• Telodendria - small branches arising from axon and collaterals near their ends.
• Axon terminals or synaptic bulbs - communicate with target cells.
• The axolemma is the plasma membrane surrounding the axon, enclosing the axoplasm (cytoplasm).
• Axonal transport moves substances through the axoplasm.
• Slow axonal transport moves cytoskeleton proteins at 1–3 mm/day.
• Fast axonal transport uses motor proteins and ATP to move vesicles and organelles at up to 200 mm/day retrogradely and 400 mm/day anterogradely.
• Three functional regions:
• Receptive region: dendrites and cell body
• Conducting region: axon
• Secretory region: axon terminal
• Structural classification of neurons:
• Multipolar neurons: one axon, multiple dendrites (over 99% of all neurons)
• Bipolar neurons: one axon, one dendrite, cell body in between (eye and olfactory epithelium)
• Pseudounipolar neurons: one fused axon dividing into two processes (sensory neurons for pain, touch, and pressure)
• Functional classification of neurons:
• Sensory or afferent neurons: carry information toward CNS (usually pseudounipolar or bipolar)
• Interneurons: relay information within CNS (multipolar, connecting with many other neurons)
• Motor or efferent neurons: carry information away from CNS (mostly multipolar)
• Specific neuron components group together:
• CNS: Nuclei (cell body clusters) and Tracts (axon bundles)
• PNS: Ganglia (cell body clusters) and Nerves (axon bundles)

Poliovirus and Retrograde Axonal Transport

• Poliomyelitis is caused by the poliovirus, impacting the CNS, especially the spinal cord, which can leads to deformity and paralysis.
• Polio is preventable through vaccination, though incurable once contracted.
• The virus accesses the CNS via muscle cells before entering motor neurons at the neuromuscular junction.
• It travels via retrograde axonal transport to reach the spinal cord.
• Other viruses like herpes simplex and rabies, and toxins like tetanus, can also invade using this method.

Neuroglia

• Neuroglia or neuroglial cells support, protect, and maintain the environment for neurons.
• They can divide and fill spaces when neurons die.
• Four types are in the CNS:
  • Astrocytes
  • Oligodendrocytes
  • Microglia
  • Ependymal cells
• Two types in the PNS:
  • Schwann cells
  • Satellite cells
• Astrocytes are large, star-shaped cells with processes terminating in end-feet.
• They anchor neurons and blood vessels, maintain brain structure, and facilitate nutrient and gas transport.
• They form the blood-brain barrier and repair damaged brain tissue.
• Oligodendrocytes in the CNS form myelin by wrapping processes around axons.
• Microglia are small, scarce cells that become phagocytic after injury, ingesting microorganisms, dead neurons, and debris.
• Ependymal cells are ciliated cells lining CNS hollow spaces, manufacturing and circulating cerebrospinal fluid.
• Schwann cells myelinate PNS axons.
• Satellite cells support neuron cell bodies in the PNS, though their functions aren't well-defined.

The Myelin Sheath

• The myelin sheath is formed from Schwann cell or oligodendrocyte plasma membranes in the PNS and CNS respectively.
• Myelination creates the myelin sheath by neuroglial cells wrapping around axons in multiple layers.
• The lipid content of myelin insulates the axon, increasing action potential conduction speed.
• Myelinated axons conduct action potentials 15-20 times faster than unmyelinated axons.
• Differences between PNS (Schwann cells) and CNS (oligodendrocytes) myelination:
• Neurolemma: outer surface on myelinated PNS axons (Schwann cell nucleus, organelles, cytoplasm), absent in the CNS.
• Number of myelinated axons: oligodendrocytes myelinate multiple axons in the CNS, while a Schwann cell myelinate only one axon in PNS.
• Timing: PNS myelination begins earlier in fetal development than in the CNS.
• Axons are generally longer than neuroglial cells, requiring multiple cells for a complete myelin sheath.
• Internodes are axon segments covered by neuroglia.
• Nodes of Ranvier are gaps between neuroglia where the myelin sheath is absent.
• Small axons can be unmyelinated in the CNS and PNS.
• White matter contains myelinated axons and appears white.
• Gray matter contains neuron cell bodies, unmyelinated dendrites, and axons, appearing gray.

Regeneration of Nervous Tissue

• Regeneration of damaged tissue is nearly nonexistent in the CNS and limited in the PNS.
• Neural tissue can regenerate only if the cell body remains intact.
• Regeneration steps:
• Axon and myelin sheath degenerate distal to injury (Wallerian degeneration), aided by phagocytes.
• Growth processes form from the proximal axon end.
• Schwann cells and basal lamina create a regeneration tube.
• A growth process enters the tube, guiding the new axon toward the target cell.
• The new axon reconnects to the target cell.

Gliomas and Astrocytomas

• Primary brain tumors originate in the brain, mostly gliomas (caused by glial cell division).
• Exposure to ionizing radiation and certain diseases are predisposing conditions.
• The most commonly affected cell is the astrocyte, resulting in astrocytomas.
• Severity ranges from mild to highly aggressive.
• Treatment varies based on tumor type and patient factors, involving surgical removal, chemotherapy, and radiation therapy.

Introduction to Electrophysiology of Neurons

• Neurons are excitable and respond to chemical signals, electrical signals, and mechanical deformation.
• Stimuli generate electrical changes across the neuron plasma membrane, conducted along the membrane.
• Two forms of electrical changes:
  • Local potentials (short distances)
  • Action potentials (entire axon length)

Principles of Electrophysiology

• Electrical changes depend on ion channels and a resting membrane potential.
• Ion channels:
  • Ions rely on protein channels because they cannot through the plasma membrane's lipid component..
  • Leak channels: always open to ion flow.
  • Gated channels: closed at rest, open with specific stimuli.
• Gated channels include:
  • Ligand-gated channels: open to specific chemical binding.
  • Voltage-gated channels: open to voltage changes.
  • Mechanically-gated channels: open or close in response to mechanical stimulation.
• Resting membrane potential: voltage when a cell is at rest.
  • Voltage: electrical gradient separated by charges across the plasma membrane.
  • Membrane potential: electrical potential across the cell membrane, a source of potential energy.
  • When a voltage difference across plasma membrane is not equal to 0 mV the cell is polarized .
  • Typical resting potential: 70 mV.
• Generation of resting membrane potential depends on: unequal ion distribution
  • Ion concentration gradients favor potassium exiting and sodium entering the cell.
  • Cytosol loses more positive charges than it gains, leading to a more negative membrane potential until it reaches resting membrane potential.
• Diffusion of an ion is determined by its concentration and electrical gradients, collectively called the electrochemical gradient.
• Sodium, potassium, and electrochemical gradients combine to give a negative resting membrane potential.
• Electrical gradients created by positive ions create and electrical potential causing a negative resting membrane potential.
• Opening a gated channel alters the membrane potential of ions, changing ability to move across the plasma membrane.
• Changes in Resting Membrane Potential:
  • Depolarization: sodium rushes into cell, making membrane potential more positive.
  • Repolarization: potassium ions exit cell, returning it to resting membrane potential.
  • Hyperpolarization: cell becomes more negative due to loss of potassium ions (cations) plus loss of anions such as chloride.

Local Potentials

• Local potentials are small, local changes in a neuron's plasma membrane potential, triggering action potentials.
• Local potentials may cause:
  • Depolarization: positive charges enter cytosol, making membrane potential less negative.
  • Hyperpolarization: positive charges exit or negative charges enter cytosol, making membrane potential more negative.
• Local potentials are also called graded potentials because they vary in size.

Action Potentials

• Action potential: uniform, rapid depolarization and repolarization of membrane potential.
• States of voltage-gated channels facilitate ion movement and membrane potential change.
• Potassium ion movement causes repolarization.
  • Voltage-gated potassium channels have two states: resting (closed) and activated (open).
  • In the resting state--channels are closed.
  • In the activated state--channels are open;
• Voltage-gated sodium channels have two gates (activation and inactivation) with three states:
  • Resting state: Inactivation gate open, activation gate closed
  • Activated state: Both gates open.
  • Inactivated state: Inactivation gate closed, activation gate open.
• Neuronal action potential lasts milliseconds, with three phases:
  • Depolarization--membrane potential rises toward zero and then briefly becomes positive.
  • Repolarization--membrane potential returns to a negative value.
  • Hyperpolarization--membrane potential becomes temporarily more negative than resting values.
• Action potential steps:

1. Local potential depolarizes axon strongly enough to reach threshold (usually 55 mV).
2. Voltage-gated sodium channels activate, sodium ions flow in causing depolarization.

• Positive feedback loop: activation of sodium ion channels and depolarization amplifies output.

3. Sodium ion channels inactivate, voltage-gated potassium ion channels activate, sodium stops flowing in, potassium begins exiting as repolarization begins.
4. Sodium returns to resting, repolarization continues.
5. Axolemma hyperpolarizes, potassium returns to resting, axolemma returns to resting potential.

Local Anesthetic Drugs

• Local anesthetics (e.g., lidocaine) provide temporary numbness during surgical or dental procedures.
• They block voltage-gated sodium channels, prohibiting depolarization and action potentials.
• They are nonselective, affecting sodium channels in muscles, causing temporary paralysis.

Refractory Period

• Refractory period: after an action potential, the neuron cannot be sufficiently stimulated to create another action potential.
  • Absolute refractory period: no additional stimulus can produce an additional action potential.
• Coincides with voltage-gated sodium channels being activated and inactivated.
• Sodium channels may not be activated until they return to their resting states.
• Relative refractory period: a strong stimulus can produce an action potential.
• Voltage-gated sodium channels have returned to the resting state.
• Potassium channels are activated and membrane is repolarizing or hyperpolarizing.

Compared: Local and Action Potentials

• Local potentials produce variable changes in membrane potentials.
• Action potentials cause maximal depolarization.
• All-or-none principle refers to events (actional potentials) which either happen completely or don't.
• Threshold must be reached for action potentials to occur.
• If a neuron isn't depolarized to threshold then no action potential will occur--action potentials are not dependent on stimulus.
• Local potentials are reversible, action potentials are irreversible.
• Signal distance is greater for action potentials versus locals:
  • Local potentials are decremental or decrease in strength over a short distance.
  • Action potentials are nondecremental; signal strength does not decrease over long distances.

Propagation of Action Potentials

• Action potentials must be conducted along entire length axon so they act as long-distance signalling service.
• Action potentials: self-propagating and only travel in one direction.
  • Each action potential triggers another in the next section of axon.
  • Sodium ion channels of each successive section of axon go into a refractory period as next section depolarizes.
• Action potential propagation down an axon is a nerve impulse.

Events of Propagation:

• Action potential is propagated down axon in following sequence of events:

Conduction Speed

• Conduction speed: rate of action potential propagation.
• Axon diameter and presence or absence of myelination both effect conduction speed--which determines how rapidly signalling can occur within nervous system.
• Larger axons have lower resistance to conduction (faster conduction)
• The presence of myelination gives rise to two types of conduction:
• Saltatory
• Continuous
• Saltatory conduction: myelinated axons, insulating qualities of myelin increases speed and efficiency of signalling. Action potentials only depolarize nodes of Ranvier and “jump over” internodes.
• Continuous conduction: in unmyelinated axons, every section of axolemma from trigger zone to axon terminal must propagate action potential, this slows conduction speed.
• Unmyelinated axon: axolemmas are leaky so current flows from axosplasm to extra cellular fluid.
• Myelinated axon: current only flows from node to node.

Classification of Axons by Conduction Speed:

• Type A fibers: fastest conduction speeds, largest diameter, Myelinated, found associated with skeletal muscle and joints.
• Type B fibers: slower conduction speeds, myelinated axons, found in efferent fibers of autonomic nervous system (ANS) and some sensory axons.
• Type C fibers: slowest conduction speeds, Smallest diameter fibers, unmyelinated axons include efferent fibers of the ANS and sensory axons, transmit pain, temperature, and some pressure sensations

Multiple Sclerosis

• Multiple sclerosis (MS): cells of immune system attack myelin sheaths within CNS
  • Causes progressive loss of myelin sheath: causes loss of current from neurons.
  • Symptoms: result from slowing of action potential propagation depend on effected region of the CNS
  • Patients exhibit changes in sensation, alterations in behavior and cognitive abilities, and motor dysfunction, including paralysis

Overview of Neuronal Synapses

• Neurons must communicate in order to carry out their functions
• Synapse: where a neuron meets its target cell (another neuron) called a neuronal synapse; can be either electrical or chemical.
• Neuronal synapses:
  • Axodendritic synapse: synapse between axon of one neuron and dendrite of another neuron
  • Axosomatic synapse: synapse between axon of one neuron and cell body of another neuron
  • Axoaxonic synapse: synapse between axon of one neuron and axon of another neuron
• Terms:
  • Presynaptic neuron: neuron sending message from its axon terminals
  • Postsynaptic neuron: neuron receiving message from presynaptic neuron at its cell body, axon, or dendrite
  • Synaptic transmission: transfer of chemical or electrical signals between neurons at a synapse
  • Allows for voluntary movement, cognition, sensation, and emotions, etc
• Avg presynaptic neuron: forms synapses with about 1000 postsynaptic neurons.
• Postsynaptic neuron: up to 10,000 synaptic connections with different presynaptic neurons

Electrical Synapses

• An electrical synapse: occurs between cells that are electrically coupled via gap junctions
  • Axolemmas nearly touching: gap junctions align channels that form pores so ions can flow through
  • Found in areas of brain: responsible for programmed, automatic behaviors such as breathing
  • Outside brain: found in cardiac and visceral smooth muscle to allow for coordinated muscle
  • Electrical current can flow directly from axoplasm of one neuron to next: creates 2 unique features:
  • Transmission is bidirectional: either neuron can be pre or postsynaptic
  • Transmission is nearly Instantaneous

Chemical Synapses

• Chemical Synapses:
  • Make up majority of synapses in nervous system
  • More efficient: convert electrical signals into chemical signals so no signal strength is lost
• Electrical and Chemical Synapses Compared: Three structural differences noted:
  • Synaptic vesicles filled with neurotransmitters located at chemical synapses
  • Synaptic cleft: small ECF filled space separates neurons; only found in chemical synapses
  • Synaptic cleft: neurons are connected via gap junctions
  • Postsynaptic neuron: has neurotransmitter receptors used to bind with neurotransmitter secreted from presynaptic neuron diffused across synaptic cleft
  • Synaptic delay: time gap between axon terminal arrival and effect on postsynaptic membrane.
• Chemical synapses vs Electrical:
  • Unidirectional
  • Allow for variable signal intensities
  • Release of more neurotransmitter from presynaptic neuron leads to stronger response at postsynaptic neuron

Events at a Chemical Synapse.

• Neuronal synapses more complicated than neuromuscular junctions:
• Multiple neurons secreting excitatory or inhibitory neurotransmitters:
• The correct order for events is:

1. Action potential in presynaptic neuron: triggers voltage-gated calcium ion channels in axon terminal to be open.
2. Calcium ions influx: synaptic vesicles cause Neurotransmitter release into synaptic cleft
3. Neurotransmitters bind to receptors: happens in the postsynaptic neuron
4. Ion channels open: leading to a local potential or an action potential if threshold is reached

Postsynaptic Potentials: local potentials in membranes of postsynaptic neuron:

• Membrane potential moves to threshold by small local Depolarization (sodium or calcium open) called an excitatory postsynaptic potential (EPSP)
  • EPSP; move the postsynaptic membrane toward threshold
• Membrane potential moves away from threshold by a small local Hyperpolarization (potassium or chloride open) called an inhibitory postsynaptic potential (IPSP)
• IPSPs
  • Are inhibatory!
  • Move the postsynaptic membrane AWAY from threshold.
• Depend on which membrane channels open.
• Only involve sodium channel opening and closing

Synaptic transmission: ending effects of neurotransmitter, finished by 3 methods:

• Some neurotransmitters: diffuse away from synaptic cleft in ECF, Neurons reabsorb ECF
• Neurotransmitter can be broken down in synaptic cleft by enzymes and reabsorbed by the membrane for reassembly.
• Some neurotransmitters are reabsorbed by a process called reuptake

Arthropod Venom

• Arthropod venom affects neuronal synapses, termed neurotoxins (spiders and scorpions include).
• Female black widow:
• Toxin causes neurotransmitter release leading to repetitive stimulation of postsynaptic neuron.
• Bark scorpion:
• venom prevents postsynaptic sodium channels from closing, membrane remains polarized and continues to fire action potentials
• Mechanisms lead to overstimulation of postsynaptic neuron.
• Common symptoms:
• Muscle hyperexcitability
• Sweating
• Nausea and vomiting
• Difficulty breathing
• Treatment/prognosis depends on venom received and availability of medical care:
• Severe cases usually require antivenin to block venom

Neural Integration

• Neurons: receive inhibitory and excitatory input from multiple neurons, each influences the action potentials
• Neural integration: integrates incoming information into a single effect
• Neural integration
  • Depends depend on which membrane channels open.
  • Only involve sodium channel opening and closing
• Summation: EPSPs and IPSPs totalled together to effect membrane potential at trigger zone
• Link between local potentials and action potentials is summation
• 2 types of summation differ in neurotransmitter release and presynaptic neurons present:
• Temporal summation: neurotransmitter released repeatedly from axon-- each local potential only generates close/ near each other.
• Spatial summation: involves simultaneous axon terminals from many presynaptic neurons releases simultaneously IPSPs are also subject to this effect

Neurotransmitters

• Undergo same pattern of use:
  • Neurotransmitters: over 100 known substances, share similar features

Neurotransmitter Receptor

• Types of receptors:
  • Neurotransmitters: bind to receptors on postsynaptic membrane to create response.
  • Ionotropic receptors:
    • Receptors as components of gated ion channels; move ions in/out of neuron
  • Metabotropic receptors:
    • Found within plasma membrane with separate ion channels; direct metabolic processes initiated when neurotransmitter binds
• Metabotropic receptors:
• G-proteins: w/many metabotropic linked to activating cascade actions; messengers
• Second messengers can open or close postsynaptic membrane.
• Cyclic adenosine monophosphate (cAMP): 2nd messenger derived from ATP with multiple functions in neurons
• cAMP can bind to a group of enzymes that can add phosphate groups to ion channels, triggers to open/close

Major Neurotransmitters:

• Neurotransmitter to receptor binds, leads to IPSP effect.
  • Most neurotransmitters have effects depending on which postsynaptic neuron receptors bind; may have single/ several receptor types

Major Neurotransmitters examples:

• Acetylcholine (ACh):

  • Cholinergic synapses bind to ACh
  • within brain and spinal cord and within autonomic nervous system
  • Largely excitatory but does exhibit some inhibitory effects in PNS
  • Synthesized from and packed into vesicles, broken down by in synaptic cleft, and reaction reabsorbed for reuse

• Biogenic amines (monoamines)- class created from amino acids to regulate homeostasis and cognition; mostly excitatory.

• Norepinephrine:

  • ANS influences heart rate, blood pressure, digestion; regulates, sleep/wake cycle, attention, feeding

• Epinephrine: used in ANS. with similar functions as norepinephrine

• Dopamine: extensively in CNS; helps coordinate movement; emotion and motivation help

• Serotonin: brainstem; axons project into areas brain; regulate mood, emotions, feeding, attention and daily rhythms

• Histamine: arousal and attention regulation

• Amino acids - has 3:

  • Glutamate: most important excitatory neurotransmitter:
  • Glycine and GABA: inhibitory opening ions w/ hyperpolarize

• Neuropeptides: variety functions

• Substance P (transmitter): from sensory carries pain/ temperature; released by neuron brain

  • Opioids (pain relievers) more than 20 to nervous system and depressants
  • Neuropeptide: involved in food/ mediates fullness

Psychiatric Disorders and Treatments:

• Psychiatric disorders processes: modifying synaptic transmission/ neuronal communication

  • Thought processes - disorders;modifying by transmission - neuron communication -Psychopharmacology (study of drugs that affect functions
  • Schizophrenia is episodes - patient beliefs repetitive to manage

• Selective serotonin reuptake inhibitors (SSRIs): neurotransmitter depression and prevent seratonin reuptake

• Anxiety disorders cause fear responses. Treatments- antidepressants, enhancers. Bipolar- elevated mood (mania)/depression - blocking channels

Neuronal Pools:

• Groups of interneurons inside the central nervous system

  • Neuronal pool: interneurons CNS: compositions,dendrites one location cell bodies
  • synaptic connections of pool define information

• Connections can be either electrical or chemical depending on neurons involved

• pools allow mental activity such as planned movement, cognition, and personality; Input/ activity signals

Neuronal Circuits

• Neural circuits patterns of synaptic connection; patterns neural two types
• Diverging: input and output of both presynaptic and postsynaptic neurons that same pattern output brain multiple single part multiple multiple
  • Incoming sensory info fromspinal cord neuronal in brain sent to process
• Converging circuits: opposite configuration of diverging- axon single
• Neural control for movement/ sensory respond collected CNS: mechanisms stable by the activity stabilized from circuits overload/ disorganized
• negative feedback mechanisms inhibitory prevent the overload/disorganized circuits control
• Fatigue synapse- transmission/weaker w/intense excitation.

Epileptic Seizures.

• Epilepsy, disorganized electrical activity in brain (seizures).

• Seizures- bursts excitatory/ a neuronal in single from within single single

• Excess inhibition circuits prevent that prevent overexcitation overwhelms

• Continuous -wave- of excitation ends to part/entire synapse fatigue

• Symptoms vary: disturbances conscious jerking movements

• Therapy: Medication/inhibitory function prevent