Neurons, Central Nervous System and Sensory Physiology Notes

Organization of the Nervous System

• The nervous system's organization involves sensory input, integration in the central nervous system (CNS), and motor output.
• Sensory receptors detect stimuli and transmit signals via sensory neurons (afferents) to the brain and spinal cord.
• The CNS, consisting of the brain and spinal cord, integrates information.
• Efferent neurons transmit signals from the CNS to effectors. These include:
  • Somatic motor neurons, which control skeletal muscles.
  • Autonomic neurons, which control cardiac muscle, smooth muscle, exocrine glands, some endocrine glands, and some adipose tissue. The autonomic nervous system has two branches:
    • Sympathetic nervous system
    • Parasympathetic nervous system
  • Enteric nervous system, which controls the digestive tract.

Model Neuron

• Dendrites receive incoming signals.
• The cell body contains the nucleus.
• The axon carries outgoing information. The axon hillock is also known as the initial segment.
• The synapse is the region where the axon terminal communicates with the postsynaptic neuron's dendrites across the synaptic cleft.
• The axon may be surrounded by a myelin sheath.

Axonal Transport

• Axons transport proteins via:
  • Slow axonal transport: Moves material by axoplasmic flow at a rate of 0.2-2.5 mm/day.
  • Fast axonal transport: Moves materials along microtubule networks using motor proteins at rates up to 400 mm/day.
    • Anterograde (forward) transport: From the cell body to the axon terminal.
    • Retrograde (backward) transport: From the axon terminal to the cell body.
• The primary function of the axon is to transmit outgoing electrical signals from the cell body to the axon terminal.

Glial Cells

• Glial cells support neurons.
• In the peripheral nervous system (PNS):
  • Satellite cells support cell bodies.
  • Schwann cells form myelin sheaths. A single Schwann cell wraps around one axon.
• In the central nervous system (CNS):
  • Oligodendrocytes form myelin sheaths. One oligodendrocyte wraps around several axons.
  • Microglia are modified immune cells that act as scavengers.
  • Astrocytes provide substrates for ATP production, help form the blood-brain barrier, take up K+, water, and neurotransmitters, secrete neurotrophic factors, and may be a source of neural stem cells.
  • Ependymal cells create barriers between compartments.

Resting Membrane Potential and Gated Channels

• Resting membrane potential is determined by:
  • $K^+$ concentration gradient.
  • The cell’s resting permeability to $K^+$, $Na^+$, and $Cl^-$.
• Gated channels control ion permeability:
  • Mechanically gated channels: Open in response to physical forces or stretch.
  • Chemically gated channels: Open in response to ligand binding.
  • Voltage-gated channels: Open in response to changes in membrane potential.
  • Threshold voltage varies from one channel type to another.

Graded Potentials vs. Action Potentials

• Graded Potentials:
  • Occur in the input signal, usually dendrites and the cell body.
  • Involve mechanically, chemically, or voltage-gated channels.
  • Ions involved: Usually $Na^+$, $Cl^−$, $Ca^{2+}$.
  • Can be depolarizing (e.g., Na^+$) or hyperpolarizing (e.g., Cl^−$).</li> <li>Strength depends on the initial stimulus; can be summed.</li> <li>Initiation: Entry of ions through channels.</li> <li>No minimum level is required to initiate; two signals close together in time will sum.</li></ul></li> <li><strong>Action Potentials</strong>:<ul> <li>Occur in the conduction signal, from the trigger zone through the axon.</li> <li>Involve voltage-gated channels.</li> <li>Ions involved:$Na^+$and$K^+$.</li> <li>Depolarizing.</li> <li>Strength is always the same (all-or-none phenomenon); cannot be summed.</li> <li>Initiation: Above-threshold graded potential at the trigger zone.</li> <li>Threshold stimulus is required to initiate; refractory period prevents signals too close together in time from summing.</li></ul></li> </ul> <h3 id="actionpotentialphases">Action Potential Phases</h3> <ul> <li><strong>Resting membrane potential</strong> is at a negative value.</li> <li>A <strong>depolarizing stimulus</strong> occurs.</li> <li>The membrane depolarizes to <strong>threshold</strong>. Voltage-gated$Na^+$channels open quickly, and$Na^+$enters the cell. Voltage-gated$K^+$channels begin to open slowly.</li> <li>Rapid$Na^+$entry depolarizes the cell.</li> <li>$Na^+$channels close, and slower$K^+$channels open.</li> <li>$K^+$moves from the cell to the extracellular fluid.</li> <li>$K^+$channels remain open, and additional$K^+$leaves the cell, hyperpolarizing it.</li> <li>Voltage-gated$K^+$channels close, and less$K^+$leaks out of the cell.</li> <li>The cell returns to resting ion permeability and resting membrane potential.</li> </ul> <h3 id="codingforstimulusintensity">Coding for Stimulus Intensity</h3> <ul> <li>The intensity of a stimulus is coded by the frequency of action potentials.</li> <li>A stronger stimulus results in a higher frequency of action potentials and thus a higher neurotransmitter release.</li> </ul> <h3 id="actionpotentialspeed">Action Potential Speed</h3> <ul> <li>A graded potential enters the trigger zone.</li> <li>Voltage-gated$Na^+$channels open, and$Na^+$enters the axon.</li> <li>Positive charge spreads along the axon by local current flow.</li> <li>A new section of the membrane depolarizes.</li> <li>The refractory period prevents backward conduction; loss of$K^+$repolarizes the membrane.</li> <li>Speed is influenced by:<ul> <li><strong>Diameter of the axon</strong>: Larger axons are faster.</li> <li><strong>Resistance of the axon membrane to ion leakage</strong>: Myelinated axons are faster.</li></ul></li> </ul> <h3 id="myelinatedaxons">Myelinated Axons</h3> <ul> <li><strong>Saltatory conduction</strong> occurs in myelinated axons, where action potentials appear to jump from one node of Ranvier to the next.</li> <li>Only the nodes have$Na^+$voltage-gated channels.</li> <li>In demyelinating diseases like Multiple Sclerosis, conduction slows when current leaks out of the previously insulated regions between the nodes.</li> </ul> <h3 id="chemicalfactorsandmembraneexcitability">Chemical Factors and Membrane Excitability</h3> <ul> <li><strong>Normokalemia</strong>: Normal blood$K^+$concentration. A suprathreshold stimulus will fire an action potential.</li> <li><strong>Hyperkalemia</strong>: Increased blood$K^+$concentration brings the membrane closer to the threshold. A stimulus that would normally be subthreshold can trigger an action potential.</li> <li><strong>Hypokalemia</strong>: Decreased blood$K^+$concentration hyperpolarizes the membrane, making the neuron less likely to fire an action potential in response to a stimulus that would normally be above the threshold.</li> </ul> <h3 id="synapses">Synapses</h3> <ul> <li><strong>Chemical synapses</strong> use neurotransmitters.</li> <li><strong>Electrical synapses</strong> pass electrical signals through gap junctions.</li> </ul> <h3 id="neurotransmitterreceptors">Neurotransmitter Receptors</h3> <ul> <li><strong>Cholinergic receptors</strong> bind acetylcholine (ACh).<ul> <li><strong>Nicotinic receptors</strong>: On skeletal muscle, in the PNS and CNS. They are monovalent cation channels (permeable to$Na^+$and$K^+$$).
  • Muscarinic receptors: In the CNS and PNS. They are linked to G proteins.
• Adrenergic receptors bind norepinephrine.
  • Alpha and beta types, linked to G proteins.

Inactivation of Neurotransmitters

1. Neurotransmitters can be returned to axon terminals for reuse or transported into glial cells.
2. Enzymes inactivate neurotransmitters.
3. Neurotransmitters can diffuse out of the synaptic cleft.

Neural Integration

• Divergence: One neuron sends signals to multiple neurons.
• Convergence: Multiple neurons send signals to one neuron.

Spatial Summation

• Excitatory neurons: Three excitatory neurons fire. Their graded potentials separately are all below threshold. Graded potentials arrive at the trigger zone together and sum to create a suprathreshold signal, generating an action potential.
• Inhibitory neuron: One inhibitory and two excitatory neurons fire. The summed potentials are below threshold, so no action potential is generated.

Temporal Summation

• No summation: Two subthreshold graded potentials will not initiate an action potential if they are far apart in time.
• Summation: If two subthreshold potentials arrive at the trigger zone within a short period of time, they may sum and initiate an action potential.

Axon Injury and Regeneration

• The proximal stump (closer to the cell body) can survive.
• The distal stump (further from the cell body) degrades.
• Survival of neurons depends on neurotrophic factors.

Central Nervous System

• Blood-Brain Barrier:
  • Astrocytes secrete paracrines that promote tight junction formation between endothelial cells.
  • Tight junctions prevent solute movement between endothelial cells.
• Metabolic Needs:
  • Oxygen: Passes freely across the blood-brain barrier. The brain receives 15% of the blood pumped by the heart.
  • Glucose: The brain is responsible for about half of the body’s glucose consumption. Membrane transporters move glucose from plasma into the brain interstitial fluid. Hypoglycemia leads to confusion, unconsciousness, and death.
• Gray vs. White Matter:
  • Gray matter: Unmyelinated nerve cell bodies, dendrites, axon terminals.
  • White matter: Myelinated axons; contains very few cell bodies.
• Spinal Cord:
  • Sensory information goes to the brain.
  • The spinal cord acts as an integrating center.
  • A spinal reflex initiates a response without input from the brain.
• Brain Stem and Cerebellum:
  • Medulla: Conveys information between the cerebrum and the spinal cord. Contains pyramids where 90% of corticospinal tracts cross. Contains centers for many involuntary functions (e.g., respiration).
  • Pons: Relays information between the cerebellum and cerebrum. Respiration, cardiac, and urinary control.
  • Midbrain: Controls eye movement, relays auditory and visual reflexes.
  • Cerebellum: Processes sensory information and coordinates movement.
• Diencephalon:
  • Thalamus: Relays and modifies sensory and motor information going to and from the cerebral cortex.
  • Hypothalamus: Center for homeostasis. Controls many autonomic and endocrine functions.
  • Pituitary: Endocrine gland that secretes neurohormones.
  • Pineal Gland: Endocrine gland that secretes melatonin.

Hypothalamus Functions

1. Activates sympathetic nervous system: Controls catecholamine release from adrenal medulla, helps maintain blood glucose concentrations.
2. Maintains body temperature: Stimulates shivering and sweating.
3. Controls body osmolarity: Motivates thirst and drinking behavior, stimulates secretion of vasopressin.
4. Controls reproductive functions: Directs secretion of oxytocin, directs trophic hormone control of anterior pituitary hormones (FSH and LH).
5. Controls food intake: Stimulates satiety center, stimulates feeding center.
6. Interacts with the limbic system to influence behavior and emotions.
7. Influences the cardiovascular control center in the medulla oblongata.
8. Secretes trophic hormones that control the release of hormones from the anterior pituitary gland.

Gray Matter of the Cerebrum

• Regions of gray matter in the cerebrum:
  • Cerebral cortex (higher brain functions).
  • Basal ganglia (control of movement).
  • Limbic system (emotion, learning, and memory).
  • Corpus callosum connects the two hemispheres of the cerebrum.

Cerebral Cortex Function

• The cerebral cortex contains three functional specializations:
  • Sensory areas: Sensory input translated into perception.
  • Motor areas: Direct skeletal muscle movement.
  • Association areas: Integrate information from sensory and motor areas; can direct voluntary behaviors.

Cerebral Lateralization

• Left Brain: Language, Verbal skills
• Right Brain: Spatial skills
• Each lobe has special functions.

States of Arousal

• Electroencephalograms (EEGs) and the sleep cycle.
• The reticular activating system keeps the “conscious brain” awake.
• Four stages with two major phases:
  • REM sleep: Brain activity inhibits motor neurons to skeletal muscle, paralyzing them; dreaming takes place.
  • Slow-wave sleep (Non-REM sleep): Adjust body without conscious commands.

Emotion and Moods

• The link between emotions and physiological functions.
• The limbic system is the center of emotion and influences physiological functions.
• Moods are similar to emotions but longer-lasting.
• Mood disorders (e.g., depression) involve sleep and appetite disturbances and alteration of mood and libido. Antidepressant drugs alter synaptic transmission.

Learning and Memory

• Two broad types of learning:
  • Associative: When two stimuli are associated with each other (e.g., Pavlov’s dog).
  • Nonassociative: Learning in response to a single stimulus.
    • Habituation: Decreased response to a repeated stimulus.
    • Sensitization: Increased response to a repeated stimulus.

Memory Types:

• Short-term: Holds 7-12 pieces of information at a time.
• Long-term: Capable of holding vast amounts of information. Consolidation converts short-term into long-term memory and involves changes in synaptic connections (long-term potentiation - LTP).

Types of Long-Term Memory:

Alzheimer's disease is a progressive neurodegenerative disease
of cognitive impairment characterized by memory loss.

Brain Function: Language

• Language skills require input of sensory information, processing in the cerebral cortex, and coordination of motor output.
• Damage to Wernicke’s area causes receptive aphasia (unable to understand spoken or visual information).
• Damage to Broca’s area causes expressive aphasia (understand spoken and written language but are unable to speak or write in normal syntax).

Brain Function: Personality

• Personality is a combination of experience and inheritance.
• Schizophrenia is an example of a brain disorder with both a genetic and environmental basis.
• In the U.S., the risk of developing schizophrenia is ~1%. The risk increases to ~10% if one parent has it.

General Properties: Sensory Division

• Sensory receptors enable us to perceive different aspects of the world around us.
• Sensory stimuli are divided into special senses and somatic senses.

Sensory Receptors

Sensory Neurons: 2-Point Discrimination

• The size of secondary receptive fields determines how sensitive a given area is to a stimulus.

Sensory Pathways in the Brain

• Olfactory pathways from the nose project through the olfactory bulb to the olfactory cortex.
• Most sensory pathways project to the thalamus, which modifies and relays information to cortical centers.
• Equilibrium pathways project primarily to the cerebellum.

Somatic Senses

• Fine touch, proprioception, vibration
  • Pathway crosses the midline in the medulla.
• Nociception, temperature, coarse touch
  • Pathway crosses the midline in the spinal cord.

Nociceptors

• Free nerve endings – pain receptors that respond to strong noxious stimuli that may damage tissue.
• Nociceptors may activate two pathways:
  1. Reflexive protective response: integrated in the spinal cord (withdrawal reflex).
  2. Ascending pathway to the cerebral cortex: becomes conscious sensation.

Referred Pain

• Referred pain from internal organs occurs when multiple primary sensory neurons converge onto a single ascending tract.

Olfaction

• Allows us to discriminate odors.
• There is a strong link between smell, memory, and emotion.
• Olfactory cells are primary sensory neurons in human olfaction, located in the olfactory epithelium in the nasal cavity, and rapidly regenerate.

Summary of Taste Transduction

• Although smell is sensed by hundreds of types of receptors, taste is a combination of only 5 sensations: amino acids, glutamate, nucleotides (nutritious, delicious, savory).
• Humans and animals may develop specific hungers, such as salt appetite.

Anatomy of the Ear

• The ear is a sense organ specialized for hearing and equilibrium.
• It can be divided into three sections.

Sound Transmission Through the Ear

1. Sound waves strike the tympanic membrane and become vibrations.
2. The sound wave energy is transferred to the three bones of the middle ear, which vibrate.
3. The stapes is attached to the membrane of the oval window. Vibrations of the oval window create fluid waves within the cochlea.
4. The fluid waves push on the flexible membranes of the cochlear duct. Hair cells bend and ion channels open, creating an electrical signal that alters neurotransmitter release.
5. Neurotransmitter release onto sensory neurons creates action potentials that travel through the cochlear nerve to the brain.
6. Energy from the waves transfers across the cochlear duct into the tympanic duct and is dissipated back into the middle ear at the round window.

Anatomy of The Cochlea

• The hair cell is modified into stereocilia, stiffened cilia arranged in ascending height.
• Tectorial membrane movement is transmitted to the stereocilia of the hair cells.

Sensory Coding for Pitch

• High-frequency waves entering the vestibular duct create maximum displacement of the portion of basilar membrane close to the oval window and are not transmitted very far.
• Low-frequency waves travel along the length of the membrane and create their maximum displacement near the flexible distal end.
• This contributes to spatial coding by location along the basilar membrane.

Eye and Vision

• The eye functions much like a camera:
  • Light enters the eye and is focused on the retina by the lens
  • Photoreceptors transduce light energy into electrical signals
  • Electrical signals are processed through neural pathways

Anatomy Summary: The Eye

• Light enters the eye through the pupil and hits photoreceptors on the retina.
• The size of the pupil modulates the amount of light.
• The shape of the lens focuses the light.

Refraction (bending) of Light & Common Visual Defects

• Hyperopia: occurs when the focal point falls behind the retina; corrected with a convex lens.
• Myopia: occurs when the focal point falls in front of the retina; corrected with a concave lens.

The Retina

• In the fovea, photoreceptors receive light directly because the intervening neurons are pushed off to the side.
• Rods are responsible for low light, night vision, black and white.
• Cones are responsible for high-acuity vision and color vision during the day; there are blue cones, green cones, and red cones (ratio ~20:1).