9: Neurons: Cellular and Network Properties

Central Nervous System (CNS)

• brain and spinal cord (main integrating center)

Peripheral Nervous System

• sensory (afferent) and efferent neurons

Nervous system reflex pathway

stimulus → sensor → input signal → integrating center → output signal → target → response

sensory (afferent) division of the PNS sends information to the CNS

• sensory receptors detect changes in the internal and external environment and transmit signals via sensory neurons to the CNS

The efferent division of the PNS carries commands from the CNS to target cells

• somatic motor neurons = control skeletal muscles

• autonomic neurons = control cardiac and smooth muscle, exocrine and some endocrine glands, some adipose tissue

enteric nervous system

• network of neurons in the digestive tract

• can function independently as its own integrating center or be controlled by the autonomic division

Neurons

• basic signaling units

• transmits info throughout the nervous system

• have dendrites (receive signals) and axons (send signals), enabling communication with other cells

• Structure:

  • cell body (soma) with a nucleus

  • dendrites branching from cell body

  • axon hillock

  • myelin sheath

  • pre-synaptic axon terminals

  • synaptic cleft

  • post-synaptic dendrites

Glial cells

• support cells for neurons

• provide structural and functional support

Synapse

• where the axon terminal communicates with its post-synaptic target cell, separated by a small space (synaptic cleft)

• where pre meets post synaptic cell

• commonly chemical synapses

  • pre releases chemical signal that diffuses across the cleft and binds to receptors on the post

Pseudounipolar neurons

• single process (axon)

• cell body off to the side

• typical of somatic sensory neurons

Bipolar neurons

• one axon

• one dendrite

• found in olfactory epithelium and retina

Anaxonic neurons

• no identifiable axon

• many dendrites

• common in CNS interneurons

Multipolar neurons

• many dendrites

• one axon

• most common in CNS and as efferent neurons

Nerves

• bundles of axons in the PNS

• sensory nerves = only afferent signals

• motor nerves = only efferent signals

• mixed nerves = carry both directions

the cell body (soma)

• the control center

• contains the nucleus and organelles for protein synthesis

• mRNA is transported to distant parts of the neuron for local protein production

Dendrites increase the surface area for receiving signals

axons

• transmit outgoing electrical signals from integrating center to target cells

• branch into collaterals, allowing communication with multiple targets

• growth cones help them

Synapse communication

• can be chemical = neurotransmitters

• can be electrical = gap junctions

• depends on neuron type and location

Synaptic cleft

• filled with extracellular matrix and adhesion molecules

• hold pre and post synaptic cells in place

Oligodendrocytes

• form myelin sheaths around multiple axons

• insulate and speed up signal transmission

• metabolic support

Astrocytes

• highly branched

• maintain homeostasis by regulating water and ion balance

• take up K+

• secrete neurotrophic factors

• provide substrates for ATP production

• form blood-brain barrier

• source of neural stem cells

Microglia

• specialized immune cells

• scavengers

• remove damaged cells and myelin

• release reactive oxygen species

Ependymal cells

• line cavities of the brain and spinal cord

• barriers between fluid compartments

• ciliated to help circulate cerebrospinal fluid

• source of neural stem cells

Schwann cells

• forms myelin around a single segment of one axon

• insulation, metabolic support, and secreting neurotrophic factors

• nodes of Ranvier = gaps between myelinated segments that are crucial for electrical signal transmission

• myelinates only one axon segment at a time

if the neuron’s cell body dies, the entire neuron dies

• if axon is severed, but cell body remains intact → proximal axon and cell body can survive

• distal axon degenerates due to lack of essential proteins

after axonal injury

• axon cytoplasm leaks out at the injury site until membrane seals the opening

• proximal axon swells as organelles accumulate

• Schwann cells send chemical signals to the cell body, alerting it to the injury and supporting potential regrowth

distal axon and its myelin sheath degenerate

• phagocytes clear away debris

loss of distal axon in somatic motor neurons causes permanent paralysis

PNS axons can sometimes regenerate

• guided by Schwann cells that secrete neurotrophic factors and provide a path for regrowth

• allows axons to potentially reestablish synaptic connections

Nervous and muscle cells are classified as excitable tissues

• because of their capacity to rapidly propagate electrical signals in response to stimuli

• can transmit a constant electrical signal over long distances

Resting membrane potential (Vm)

• separation of electrical charges across the cell membrane

• Main factors determining membrane potential:

  • uneven distribution of ions (Na+, Cl-, Ca2+ higher outside) + (K+ higher inside)

  • differing membrane permeability to these ions

• membrane more permeable to K+ than to Na2+ or Ca2+ making K+ the primary contributor to Vm

• K+: Ek = -90 mV

• cell: -70 mV (other ions contribute)

• neurons slightly permeable to Na+ at rest

  • Na+ influx makes mV more positive

membrane potential of cells

• from the combined effects of all ions that can cross the membrane

• each ion’s contribution depending on both its concentration gradient and its membrane permeability

Goldman-Hodgkin-Katz (GHK) equation

• calculates the membrane potential (Vm) by considering the relative permeabilities and concentrations of Na+, K+, and Cl-

• P represents permeability for each ion

• [ion] = ion concentrations, depending on outside and inside for context

• if permeability = 0, then that ion doesn’t contribute to the membrane potential

How do cells change ion permeability?

• Via opening or closing existing membrane channels

• inserting or removing channels from the membrane

• 4 selective ion channels in the neuron:

• Na+

• K+

• Ca2+

• Cl-

Channel conductance (G)

• how easily ions flow through a channel

• depends on the channel’s gating state and protein isoform

Gated channels activation mechanism

• mechanically gated channels respond to physical forces (pressure, stretch)

• chemically gated channels respond to ligands (neurotransmitters or intracellular signals)

• Voltage-gated channels respond to changes in membrane potential. Crucial for electrical signaling in neurons

• Each channel type has multiple subtypes and isoforms causing different opening/closing speeds and responses to modulators like phosphate groups

Channel inactivation

• closing spontaneously after opening even if the activating stimulus persists

• return to a closed state after repolarization

Graded Potentials

• changes in membrane potential that can be either depolarizations or hyper-polarizations

• mainly in the dendrites and cell body of neurons

• amplitude is directly proportional to the strength of the triggering stimulus

  • larger stimuli = stronger graded potentials

  • smaller stimuli = weaker graded potentials

• Initiated when chemically gated ion channels open in response to chemical signals from other neurons, allowing ions to move into or out of the neuron

• can result from closing of ion channels = decreases ion movement across the membrane

• graded potentials decrease in strength as they move away from the point of origin b/c of cytoplasmic resistance and current leak

Hyperpolarizing graded potentials

• either Cl- entering or K+ leaving the neuron

• inside of cell becomes more (-)

Trigger zone

• site where action potentials are initiated

• Ex: axon hillock and initial segment in efferent neurons and interneurons

• acts as the integrating center of the neuron and contains high concentration of voltage-gated Na+ channels

• graded potentials must reach threshold at the trigger zone to initiate an action potential

Depolarizing graded potentials are excitatory

• bring membrane potential closer to threshold

• increases likelihood of firing an action potential

Hyperpolarizing graded potentials are inhibitory

• move the membrane potential further from threshold, decreasing the likelihood of firing

Excitability

• ability of a neuron to respond to a stimulus and fire an action potential

Action potentials

• uniform electrical signals

• travel from a neuron’s trigger zone to the end of its axon without losing its strength, unlike graded potentials

Voltage-gated Na+ channels open sequentially

• open along the axon

• allow Na+ to enter and reinforce depolarization, maintaining the action potential’s amplitude (about 100 mV) throughout its journey

Conduction

• high speed movement of the action potential along the axon, ensuring the signal remains strong from start to finish

Action Potentials are all-or-none events

• occur fully if the stimulus reaches threshold or not at all if threshold not reached

• amplitude does not depend on the strength of the initiating graded potential

Conductance

• movement of ions across a cell membrane, allowing electrical currents to flow due to ion channels opening or closing

Conduction

• rapid and undiminished transmission of an electrical signal along the axon of a neuron

Rising phase

• rapid increase in Na+ permeability

• allows Na+ to enter the cell

• cause depolarization and reversal of membrane polarity, peaking about 30+ mV

Falling Phase

• slower-opening voltage gated K+ channels increase K+ permeability

• K+ exits the cell, making the membrane potential more negative and returning it toward resting levels

After-hyperpolarization (undershoot)

• K+ channels remain open after the membrane potential reaches -70 mV

• potential approaches the K+ equilibrium potential (Ek = -90mV)

Key Ion Movements

• Na+ influx causes depolarization

• K+ efflux restore and hyperpolarizes the membrane

• the action potential is a result of sequential changes in membrane permeability to Na+ and K+, driven by the opening and closing of specific voltage-gated ion channels

Resting membrane potential (Vm)

• created by the separation of electrical charge across the cell membrane

Factors that determine membrane potential

• uneven distribution of ions

  • Na+, Cl-, Ca2+ higher outside

  • K+ higher inside

• differing membrane permeability to these ions

• membrane more permeable to K+

Neural communication

• relies on both electrical and chemical signals to transmit information throughout the nervous system

What determines specificity in neural signaling?

• the types of signal molecules (neurotransmitters) released by neurons

• presence and type of receptors on target cells

• precise anatomical connections at synapses between neurons and their targets

Synapses

• specialized regions where neurons connect with their target cells, enabling targeted and regulated communication

• contains an axon terminal of the pre-synaptic cell and membrane of the post-synaptic cell

information transfer in neural reflexes

• from the pre-synaptic cell to postsynaptic cell (neuron or non-neuronal cell)

• 
  

most neuron to neuron synapses

• involve the presynaptic axon terminal connecting to the dendrites or cell body of the postsynaptic neuron

• some synapses can occur on the axon or axon terminal of the postsynaptic cell

Electrical Synapses

• transmit electrical signals directly through gap junctions, allowing rapid and often bidirectional communication

• found in CNS neurons, glial cells, cardiac and smooth muscle, nonexcitable cells

• Gap junctions allow both electrical currents and chemical molecules to pass between cells, facilitating synchronized activity

Chemical synapses

• most common type in the nervous system

• use neurocrine molecules (neurotransmitters) to transmit information across the synaptic cleft

• converts an electrical signal in the presynaptic cell into a chemical signal that binds to receptors on the target cell

Neurocrine molecules

• neurotransmitters, neuromodulators, neurohormones

• distinct signaling roles:

  • neurotransmitters and neuromodulators act locally (paracrine)

  • neurohormones distributed systemically via the blood

Neurotransmitters

• produce rapid responses at synapses

Neuromodulators

• act at both synaptic and nonsynaptic sites and have slower, long lasting effects

Autocrine signaling

• when neurocrine molecules act on the same cell that secreted them, in addition to their paracrine

ionotropic (receptor channels) neurocrine receptors

• ligand-gated ion channels mediating fast responses

metabotropic neurocrine receptors

• G protein coupled receptors, GPCRS

• mediate slower responses via second messenger systems

• most neuromodulators bind to GPCRS, can regulate ion channel activity indirectly

Synaptic vesicles

• found in axon terminal

• store neurotransmitters

• docked and prepped for release or reserve pools

Neurotransmitter synthesis

• happens in both nerve cell body and axon terminal

• polypeptide neurotransmitters = in the cell body, packaged with modifying enzymes and transported to the terminal to be processed into active peptides

• smaller neurotransmitters (ACh) = in the axon terminal using enzymes delivered from the cell body

Neurotransmitter release

• triggered by action potential

• depolarization at the axon terminal opens voltage-gated Ca2+ channels

• Ca2+ influx happens

• exocytosis of synaptic vesicles contents (neurotransmitters) into the synaptic cleft

Termination of neurotransmitter action done by:

• reuptake into the presynaptic terminal or glial cells

• enzymatic breakdown in the synaptic cleft

• diffusion away from the synapse into the bloodstream

post-synaptic cell responds when neurotransmitter binds to its receptors

• magnitude of the response reflects the number of vesicles that released neurotransmitter

a single action potential at the axon terminal releases a fixed amount of neurotransmitter

• neurons encode information by varying the frequency of action potentials rather than the amount released per action potential

Stimulus Duration

• represented by the duration of a series of action potentials

• stimulus strength is encoded by the frequency of action potentials

  • stronger stimulus = more action potentials per second

  • increased neurotransmitter release

Graded potentials

• if above the threshold at the trigger zone, initiate bursts of action potentials

• amplitude of graded potentials increase, frequency of action potentials increases

Divergence

• when one presynaptic neuron branches to influence multiple postsynaptic neurons, amplifying the signal across many targets

Convergence

• when multiple presynaptic neurons provide input to smaller number of postsynaptic neurons

• allows integration of information from many sources onto fewer targets

Synaptic plasticity

• nervous system’s ability to change synaptic activity

• either facilitation (enhanced activity) or depression (decreased activity)

Fast post-synaptic responses

• mediated by receptor channels

• when neurotransmitters bind, these channels open

• ions flow rapidly and cause quick, short-lived changes in membrane potential (fast ones)

Excitatory postsynaptic potentials (EPSPs)

• more Na+ enters the cell, leading to depolarization and making neurons more likely to fire an action potential

Inhibitory Postsynaptic Potentials (IPSPs)

• more K+ leaves or more Cl- enters the cell

• hyperpolarization and making neurons less likely to fire

Slow Postsynaptic responses

• mediated by G protein-coupled receptors linked to second messenger systems

• responses take longer to initiate and last longer