Neurons: Structure and Function

Nervous System - Neurons

• Controls and coordinates the body along with the endocrine system
• Neurons transmit signals to specific target cells at synapses
• Diverse in shape, size, and branching
• Includes all of the neurons in the body
• Signals move through neurons at 100 m/s

Nervous System - Parts of Neurons

• Neurons have four parts

Dendrite

• Receives input from other neurons
• Can receive thousands of synaptic contacts
• Synaptic inputs can be inhibitory or excitatory, affecting action potential likelihood

Cell Body (Soma)

• Integrates signals received by the dendrites

Axon

• Conducts and propagates the action potential
• Axon initial segment is the typical site of action potential initiation
• Bundles of axons are called tracts in the CNS and nerves in the PNS

Presynaptic Terminals

• Outputs signal to another cell releasing neurotransmitters across the synapse
• Neurotransmitters bind to receptors on target cells which activates the target cell

Nervous System - Types of Neurons

• Afferent neurons relay sensory signals to integrative centers of the CNS
• Efferent neurons relay signals from the CNS to target cells under nervous control
• Interneurons are entirely within the CNS
• Neurons can be classified by processes emanating from the soma
• Unipolar neurons have one process
• Bipolar neurons have two processes
• Multipolar neurons have three or more processes

Nervous System - Glial Cells

• Surround neurons
• The ratio of glial cells to neurons varies; more complex animals tend to have more glacial cells per neuron
• In vertebrates, there are four types of glial cells

Schwann cells and oligodendrocytes

• Envelop axons
• Myelin sheath consists of multiple concentrically wrapped layers of glial membrane
• Insulate the axon increasing the velocity of action potential propagation

Astrocytes

• Regulate extracellular ion concentrations
• Supply metabolic substrates to neurons
• Take up neurotransmitters

Microglial Cells

• Mediate immune responses
• Act as phagocytic cells

Nervous System - Circuits

• Nerves are organized into circuits
• Reflexes are a simple, stereotyped behavioral response to a distinct stimulus
• Example: Startle response in cockroaches

Startle Response in Cockroaches

• Wind receptors detect air currents and sound waves
• Sensory neurons at the base of the hair generate a series of action potentials
• Sensory neurons excite interneurons
• Interneurons excite leg motor neurons
• Leg motor neurons excite the extensor muscles of the leg
• The startle response happens in under 150 milliseconds

Nervous System - Resting Membrane Potential

• Resting membrane potential (Vm) is the normal electrical potential across the cell membrane of a cell at rest
• Ranges between -40 mV and -60 mV in most neurons
• The inner membrane surface is negative compared to the outer membrane surface
• Cells maintain high concentrations of K+ and lower concentrations of Na+ and Cl- in the intracellular fluids compared to extracellular fluid
• Differences in ion concentrations are maintained by active transport (Na+-K+ pump) and passive diffusion

Nervous System - Equilibrium Potential

• Equilibrium potential is the membrane potential at which an ion species is at electrochemical equilibrium
• Concentration-diffusion forces offset electrical forces
• No net flux of that ion species occurs across the membrane
• Ions are not at equilibrium potential inside the body; K+ is constantly leaking out, and Na+ is constantly leaking in

Nervous System - Pumps

• The Na+-K+ pump is an electrogenic pump that produces a voltage difference across the membrane
• Generates membrane potential
• Pumps three Na+ ions for every two K+ ions
• Counteracts the diffusion of these ions through the cell membrane

Nervous System - Action Potential

• Generated when nerves are stimulated causing a local change in membrane potential
• Change in membrane potential is propagated to carry the signal along the nerve
• Depolarization occurs when the inside of the cell becomes more positive
• Hyperpolarization happens when the inside of the cell becomes more negative
• Action potential is a reversal of membrane potential from about -65 mV to +40 mV
• Lasts about 1 millisecond
• Resting membrane potential is then restored

Basic Action Potential Steps

• The membrane is locally depolarized past the voltage threshold, that is required to trigger the action potential
• The membrane continues to become depolarized (rising phase), and the inside of the cell becomes more positive compared to the outside of the cell (overshoot)
• The inside of the cell is then repolarized (falling phase)
• The cell briefly goes lower than resting membrane potential (undershoot) before returning to resting membrane potential
• Action potentials are all-or-nothing responses

Action Potentials

• If the voltage threshold is reached, an action potential is triggered
• Once action potentials are triggered, they propagate without losing strength
• They rely on two channels:
• Voltage-gated ion channels whose opening depends on the membrane potential
• Leak channels that allow ions to move down their electrochemical gradients and are always open

Steps of an Action Potential

• A stimulus depolarizes the membrane past the threshold
• Rising phase: Voltage-gated Na+ channels open in response to depolarization
• Makes the membrane more permeable to Na+, which rushes into the cell and causes the inside to become more positive
• Falling phase: Voltage-gated Na+ channels are inactivated making cells less permeable to Na+
• After a delay, voltage-gated K+ channels also open, making the cell membrane more permeable to K+ which rushes out
• Recovery phase: voltage-gated K+ channels stay open for a few milliseconds, causing a brief period of hyperpolarization
• At this point, voltage-gated Na+ channels recover and can be opened again

The Voltage-Gated Na+ Channel

• Has four domains, each containing six membrane-spanning segments
• The four domains surround the pore and allow Na+ to move through the membrane
• Membrane-spanning segment 4 of each domain contains the voltage-sensor region
• Contains positively charged amino acids
• The P loop connecting segments 5 and 6 lines the pore ensuring selectivity for Na+
• The cytoplasmic loop between domains III and IV mediates the inactivation of the pore
• Action potentials are propagated down axons

Action Potential Propagation

• Along the axon is unidirectional due to
• The inactivation period of voltage-gated Na+ channels, where inactivation persists until the membrane potential returns to near its negative resting state
• Hyperpolarization caused by the voltage-gated K+ channels

Action Potential - Refractory Periods

• Absolute refractory period: ~1 ms after an action potential
• It is not possible to generate another action potential because voltage-gated Na+ channels are inactivated)
• Relative refractory period: a few milliseconds after an action potential
• It's harder to generate another action potential because the membrane is hyperpolarized due to voltage-gated K+ channels

Action Potential - Speed of Propagation

• Depends on two factors
• Axon diameter: greater diameters result in faster action potential propagation
• Myelination: myelinated axons propagate action potentials faster than non-myelinated axons
• Nodes of Ranvier are gaps in the glial wrapping where action potentials can occur in myelinated axons
• These cells exhibit saltatory conduction by which, the action potential jumps from node to node
• Additional factor
• Temperature: higher temperatures result in faster propagation

Introduction to Synapses

• Synapses are specialized sites of communication between a neuron and another cell
• Synapses can be
• Neuron to Neuron
• Neuron to Effector Cell
• Sensory Cell to Neuron
• Presynaptic neurons influence the function of the postsynaptic cell
• Action potentials in the presynaptic cell cause synaptic transmission to be released
• Synaptic transmission is the signal sent by the presynaptic cell affecting the postsynaptic cell
• Synaptic transmissions change the membrane potential potentially causing action potential in the postsynaptic cell

Electrical Synapses

• Chemical synapses are more commonly seen but some synapses are electrical
• Chemical and electrical synapses play different functional roles
• In an electrical synapse
• The current of the action potential spreads directly from one cell to another making it fast
• Cells using electrical synapses have specialized gap junctions (connexons) that bridge cells, linking their cytoplasm and bringing the two cells to about 3.5 nm apart
• Electrical signals weaken slightly as it moves from one cell to another
• Useful in escape circuits, like the crawfish tail-flip

Chemical Synapses

• Rely on action potential that must be transduced into a chemical signal (neurotransmitter)
• Synaptic vesicles in the presynaptic cell store thousands of neurotransmitter molecules
• Presynaptic cells have active zones with neurotransmitters which are released
• The postsynaptic membrane has postsynaptic densities where receptor proteins for neurotransmitters are located

Steps of Chemical Synapses

• Action potential depolarizes the presynaptic terminal opening voltage-gated Ca2+ channels
• Ca2+ moves into the cell because it's less concentrated inside than outside the cell
• Ca2+ influx triggers neurotransmitter release into the synaptic cleft via calcium-dependent exocytosis (fusion of vesicles to the presynaptic membrane)
• Neurotransmitter molecules bind to specific receptor proteins in the postsynaptic membrane
• The neurotransmitter is degraded by enzymes which is then taken back into presynaptic cells

Chemical Synapses - Types

• Type partially depends on the receptor that the neurotransmitter binds to
• There are two types:

Ionotropic receptors

• Directly alter permeability to ions producing rapid changes in membrane potential because they allow ions to flow into the cell
• Ligand-gated ion channels

Metabotropic receptors

• Trigger a signaling cascade of second messengers
• Have slow but long-lasting effects on postsynaptic cells
• Chemical synapses are slower than electrical synapses

Chemical Synapses - Advantages

• They can amplify the response in the postsynaptic cell
• Chemical synapses can be either excitatory or inhibitory
• Chemical synapses are more finely controlled and plastic
• Presynaptic cells can release differing types or amounts of neurotransmitter
• Postsynaptic cells can have different types and numbers of receptors

Neurotransmitters - Classes (I)

• Can be broadly divided into two classes

Small-Molecule

• Usually comprise of amino acids and their derivatives
• Synthesized in axon terminals from metabolic precursors
• Packaged into small synaptic vesicles by vesicular transporter molecules on the surface of vesicles
• Example: dopamine (derived from tyrosine in the axon terminal)
• Released by calcium-dependent exocytosis

Neurotransmitters - Classes (II)

• Neuropeptides are chains of 3-55 amino acids
• Synthesized on ribosomes in the soma as propeptides containing several copies of the neurotransmitter
• Large dense-cored vesicles transport the propeptides to axon terminals
• Propeptides are cleaved inside the vesicles to make the active neurotransmitters
• Peptide transmitters require a higher frequency of presynaptic action potentials compared to small-molecule transmitters
• Exocytosis of these vesicles occurs not at active zones and requires greater Ca2+ influx
• Neuropeptides are always broken down after release

Neuronal Transporters

• Synthesized in the soma then delivered to the appropriate areas such as the axon terminal
• There are a lot of different neurotransmitters and receptors
• CNS neurotransmitters can be divided functionally and by location

Types of Neurotransmitter

• Most in the CNS are small-molecule neurotransmitters
• Glutamate (excitatory)
• GABA and glycine (inhibitory)
• Amines like acetylcholine, norepinephrine, dopamine, and serotonin
• Are in fewer cells of the CNS but are widespread
• Produce a slow response in postsynaptic cells
• Peptides are common in the CNS and released with small-molecule neurotransmitters
• Neurons can contain and release more than one kind of neurotransmitter
• Cotransmitters are released by a single neuron
• Neurons often contain and release a small-molecule neurotransmitter and one or more neuropeptides
• Transmitters can be released from the same vesicle if they are the same type (dopamine and GABA)
• Most neurotransmitters are conserved across animal taxa

Neurotransmitter Release

• Vesicles containing neurotransmitters are prepared by the cell
• After an influx of Ca2+ ions, the vesicles dock with the axon membrane
• Vesicles will either
• Fuse fully with the membrane (classical exocytosis) and release neurotransmitter
• Fuse only partially with the membrane (kiss-and-run fusion) and release neurotransmitter

Vesicle Retrieval

• In classical exocytosis, the vesicle is then endocytosed with the aid of clathrin and dynamin
• Kiss-and-run fusion does not fuse the vesicle fully negating the need for the full process of endocytosis

Synaptic Potentials (PSPs)

• Postsynaptic potential are generated in the postsynaptic cell
• This takes place after neurotransmitters from a presynaptic cell binds
• PSP is a short change in the resting membrane potential of the postsynaptic cell
• Excitation occurs causing an increase in the probability of action potential which creates excitatory postsynaptic potentials (EPSPs)
• Inhibition occurs causing a decrease in the probability of action potential, which creates inhibitory postsynaptic potentials (IPSPs)
• The Changes in membrane potential in postsynaptic cells are controlled by changes in the permeability of the cell’s membrane to ions
• For example
• When acetylcholine binds to its receptor, the receptor which is also an ion channel opens up thus allowing Na+ and K+ to enter/leave the cell easier
• Most neurotransmitters affect more than one kind of neurotransmitter receptor
• The effects depend on the type of receptors

Types of Neuron

• Acetylcholine
• Excites skeletal muscle cells
• Inhibits heart muscle cells as these possess different receptors i.e. nicotinic receptors in muscle vs. muscarinic receptors in heart

Neuron Types - Based on Location

• Interneurons are confined to the CNS
• Sensory neurons convey information to the CNS
• Motor neurons convey information out of the CNS to control muscles or other effectors
• Effectors are cells such as those for motion or secretion under the direction of the nervous system

Nervous System Organization - Central Nervous System

• The CNS is composed of the brain and spinal cord
• Consist of support cells and neurons
• Works to achieve integrative functions, mainly
• Grey matter - processes and synaptic contact
• White matter - Myelinated axons within tracts
• Organized into the mid brain, hind brain and forebrain
• The cerebral cortex prominence increases across species of animals with heightened complexity

Nervous System Organization - Location of Functional Regions

• Neurons in various regions of the brain have disparate functional roles
• functional regions exist but are not singularly involved in single functions only
• Brain maintains maps that relay information in regards to the body
• Using somatotopic maps, that relay the sensory information to the cortex

Nervous System Organziation - Mammalian Brain Regions

• The information below is a breakdown of the major Mammalian Brain divisions, brain subdivisions, area, and major functions

Forebrain

• Telencephalon: Cerebral cortex - responsible for Higher sensory, motor, and integrative functions
• Hippocampus: responsible for learnings and memory
• Basal ganglia: responsible for Motor controls
• Limbic system: responsible for Emotions

Diencephalon

• Thalamus: responsible for Major sensory relay Hypothalamus: responsible for Homeostatic and endocrine regulation along with circadian clock

Midbrain

• Mesencephalon: Superior colliculus - Visual integration
• Inferior colliculus: Auditory integration

Hindbrain

• Metencephalon: Cerebellum - Motor coordination
• Pontine motor nuclei: Descending motor control
• Myelencephalon: Medulla oblongata - Autonomic and respiratory control

Nervous System Organization - Peripheral Nervous System

• The PNS is the culmination of all motor sensory process outside of the CNS
• Composed of Nerves which carry axons of neurons bundled together
• Further separated into
• cranial nerves - that connect to the brain
• spinal nerves - that connect to the spinal cord
• Consists of the somatic and autonomic parts

Peripheral Nervous System - Somatic

• The part of the PNS that controls the skeletal muscles through
• Voluntary control
• Somatic-motor neurons that directly synapse to muscle fibers while releasing acetylcholine that excites cells

Peripheral Nervous System - Autonomic

• The function under this system is to control effectors such as cardiac and smooth muscle (eye/blood vessel/ gut etc glands)
• Contains 3 divisions
  • Parasympathetic - Utilizes rest and digest
  • Sympathetic - Utilizes elevated functions for fight or flight
  • Enteric - Controls gut motility

Autonomic division notes

• Can occur
• Have Periphery Synapse - as Extra - Synapse between the CNS and effector locations
• Location is within the autonomic ganglia or neuronal cell bodies
• Nerves for this
• Can either be
• Pre - ganglionic Neurons that release ACh and or are Cholinergic
• Post - ganglionic Neurons that either releases ACh or Adrenergic as Norepinephrine

The PNS contains divisions such as sympathetic and parasympathetic

• Parasympathetic releases nerves from the sacral and cranial region of the CNS
• Alternatively Sympathetic preganglionic neuron release is from the thoracic and lumbar region of the CNS

Organzation of the Nervous System - Nervous System Diversity

• Central Nervous System' are
  • Ganglionic - typically found in annelids, mollusks and arthropods CNS which is a chain of segmental ganglia
  • typically the parts are linkers of chained ganglia by bundles of axons called connectives that are (ventral,and solid)
  • Columnar - A structure for vertebrates with a continuous column of nervous tissue that is (dorsal, filled w/ cerebrospinal fluid, a pair of spinal nerves per vertebra, axons of sensory neurons)

Structural Features Associated in Nervous Systems

• Axons of sensory Neurons typically enter the spinal cord in the dorsal roots of nerves
• Ventral Roots typically contain somatic and motor neurons
• The parts fuse together via dorsal and ventral connections

Nervous Systems Diversity - Organization

• This type occurs when Neurons are collected into internal areas rather than randomly
• Additionally the concentration of system can be achieved via Cephalization ie. The brain! Which allows fore brain for complex features

Overview of Sensory Function

Anatomical structured called sense organ

• This organ receives senses thru various types of stimuli that are bound to membrane
• The nervous system then converts sensory energy into a electrical signal a process called sensory transduction
• And then conducted by the system either a action potential or synapse

Sensory Modulation

• Is determined by the frequency in which the signal travels ie. action potential
• Can have
  • Adaption - reduced firing action potentials
• Receptor specialization - Phasic - rapid stimulation that tapers off with constant changes
  • Tonic - Long term steady state with decrease rates of action signals
• All is based on 1 - sensory modality that is how the signal relays thru body

Sensory Modality Types

• Various types in animalia that include touch , smell and audio among other animals

Stimuli types

• Light, magnetic waves
• Sound, Touch and Balance
• Smell or Taste
• There transducing properties for electrical

Classifying Receptors

• Transduce through either
  • Ionotropic Transduction or signal receptor molecule that effects cell permeability of ions
  • Metabotropic Transduction or intra - cellular change via cell - G - protein bound

Other types of Receptors occur based on location

• Location
• Exteroceptors which activate outside stimulus
  • Interoreceptors which activate inside stimuli

Separations of Sensory Cell Types occur from 5 classes (hearing, taste, touch, vision

• The cells either
• Activate and synapse with an outside location or
• Transfer directly into the CNS
• However some types of signal such as sound are non transferrable via central means

CNS Signaling

• The CNS receives those singles from both types of receptors
• particular brains receive signals from different receptors,
  • There is a specialization in Touch signals

Touch is facilitated by mechanoreceptors

• This is either through the body or thru specialized structure
• Such as Insects and specialized sensillum on exoskeleton
• or mammalian like skins by dendrites

Structure of Receptors

• Movement creates a opening and creates a ion in the nerves base
  • The trigger will yield amount of action potential

Mammalian organization has the sensory units called dorsal root ganglia

• These gangs release sensory info adjacent to spinal region
  • Each will be specialized at different stimulation types that are piezo channel activation

Touch Receptors Types

• There are four types of touch stimulation within the four main endings of the skins

Disc - Merkel

• This area contains texture and shapes edges, typically associated to tonic signals

- Meissner corpuscles

• Typically has six or two endings to for sensor units that are touch senstiive and phasic receptors

Ruffini endings

• This type contains tonic signal that releases pressure on receptor

Pacinian corpuscles

• This type senses only vibration typically releases phasic stimulation and are ensheathed deep into inner layers

Specialization in audio sensory - Animals

• Has the need for mechanorecpetors and air and water
• Example insect have tympanal membrane that displace sound. -- Movement signals mechanorecpetors which are attached to that movement. IE moth is preyed on

Audio processing of vertebrates

• Relays on the hair cellular that converts sound into signals that can be released unto cns through neural actions
• Typically from short to the largest microvilli

Other systems of sensing

• Vertebrates that specialize in Tetrapods have external and inner mid regions
• Such as the external region which is pinna and is usefull for external sounds/ middle ossicles help transmit sounds and internal ear for waves