Neural Signaling: Neurons and Glial Cells

Neural Signaling

• Neurons and glial cells make up the nervous system
• Ability to detect and respond to stimuli is critical for an organism's survival and maintaining homeostasis
• Information flow through the nervous system involves reception, transmission, and integration
• The endocrine system works with the nervous system to regulate physiological processes, endocrine regulation is slow, nervous responses are rapid

Neurons and Glial Cells

• Neurons transmit electrical signals or nerve impulses
• A typical neuron consists of a cell body, dendrites (receiving input), and an axon (sending output)
• Axons may branch into axon collaterals, with terminal branches ending in synaptic terminals that contain neurotransmitters
• Axons are wrapped together by connective tissue into nerve bundles
• Schwann cells surround axons outside the central nervous system, forming a myelin sheath for insulation and better transmission
• Nodes of Ranvier are gaps in the myelin sheath that allow current flow, causing 'saltatory' (jumping) conduction of action potentials
• Inside the CNS, bundles of axons are referred to as tracts or pathways and are supplied with blood by arteries and veins
• Outside the CNS neuronal cell bodies are called ganglia, in the CNS they are called nuclei
• Glial cells support neurons metabolically and structurally
• Neurobiology studies chemical messengers, >50 identified chemical compounds for neuron/glial cell communication
• Neurogenesis produces new neurons

Types of Glial Cells

• Astrocytes provide physical support, nutrients, regulate extracellular fluid composition, form the blood-brain barrier and communicate with neurons
• Microglia secrete growth factors, mediate injury responses, and prevent infection
• Oligodendrocytes form myelin sheaths around neurons in the CNS
• Ependymal cells ciliated cells lining internal CNS cavities; neural stem cells producing new neurons and glial cells; help produce cerebrospinal fluid

Transmitting Information Along the Neuron

• Neurons use electrical signals for transmission along axons
• Animal cells compared to extracellular fluid are internally more negative
• Plasma membrane of a neuron at rest is polarized, creating a potential energy difference
• Voltage causes charged particle flow between two points
• Neurons and muscle cells are excitable due to their rapidly changing membrane potential
• Neuron resting potential is ~ -70 mV, measured by voltmeter
• Potassium intracellular concentration is 10X > extracellular fluid
• Extracellular sodium concentration is ~ 10X > intracellular fluid
• Selective ion channels facilitate this maintaining asymmetric distribution
  • passive
  • voltage-activated
  • chemically-activated
• Selective ion channels allow Na+, K+, Cl-, and Ca2+ to flow
• Both voltage and chemically activated are controlled by gates
• Ion pumps contribute to asymmetric distribution

Equilibrium and Resting Potential

• Potassium channels are the most common passive ion channel, more permeable to K+
• Potassium leak out following concentration, increases positive charge outside
• Electrical influence flows, and it is forced back in
• Equilibrium potential occurs when electrical attraction equals concentration gradient
• Potassium equilibrium potential is ~ -80 mV
• Sodium equilibrium potential is ~ +40 mV
• Membrane is more permeable to K⁺ than Na⁺, neuron resting potential is close to K⁺ equilibrium
• Sodium-potassium pumps maintain gradients, transporting Na⁺ out and K⁺ in, for every 3 Na⁺ out, 2 K+ in, and [Na⁺] outside, ↗ [K+] inside

Neuron Excitability and Potentials

• Neurons are excitable responding to transmembrane potential changes
• Altering with the resting potential (electrical, chemical, or mechanical stimulus) increases the membrane permeability to sodium ions
• Depolarization occurs when a stimulus reduces membrane potential negativity
• Depolarization is an excitatory and strengthens action potential
• Hyperpolarization reduces neuron firing, becomes more negative.
• Graded potential is the local response signaling short distances and varies with stimulus strength
• When stimulus is strong enough, voltage declines >> the threshold level that causes neuron to fire nerve impulse/action potential
• Voltage-activated ion channels respond to changes in transmembrane potential by opening/closing
• Increased flow of ions down concentration results in depolarization with sodium and potassium channels

Action Potential: Sodium Influx and Potassium Efflux

• A membrane potential reaches ~-55 mV, the threshold, it fires an action potential
• At the threshold the majority of sodium channels open rapidly changing membrane potential
• The neuron membrane reaches zero potential, overshooting to +35mV for momentary polarity reversal
• The quick rise and fall is called spike
• Resting state >> stimulus causes depolarization >> threshold reached >> action potential >> repolarization and return to resting state
• The entire process, depolarization and repolarization, in < 1 millisecond
• During the action potential, no other action potential is produced
• Absolute refractory period describes NO stimulus to produce action protentional
• Relative refractory period describes when is stronger stimulus to occur, and lasts milliseconds
• Action potential conforms to all-or-none response as it fires exceeding the threshold, or doesn't fire
• No variation of a single impulse, the level of intensity depends on the number of neurons stimulated and frequency to discharge
• Action potentials propagate along the axon, building themselves as they move in a self propagating action
• Action potentials produce sufficient depolarization; repolarization occurs behind
• Action potential moves as a wave of depolarization cell body from end of axon

Continuous and Saltatory Conduction

• Propagation is continuous conduction, in unmyelinated neurons
• Most axons transmit impulses at ~1 to 10 m/s
• Transmission speed is proportional to axon diameter (less resistance), and invertebrates have evolved with large diameter to conduct faster
• Myelin in vertebrates allows effective electrical insulation besides nodes of Ranvier
• The myelin is derived from neuroglial cells Schwann in the PNS, oligodendrocytes in the CNS
• Saltatory conduction is more rapid in myelinated neurons
• Depolarization skips along axon from one node of Ranvier to the next with concentration of Nat & K+ channels, distance affects transmission speed
• With farther nodes, less axon must depolarize making the impulse faster with less energy and fewer ions being required
• Sodium rapid diffuse from node of Ranvier to the next in myelinated in saltatory with action potential leaps node to node conducting up to 50 times faster than unmyelinated

Neural Signaling Through Synapses

• Signals pass between cells at synapses, between two neurons or a neuron and an effector
• Synapse location allows 2 cells very close to each other with signal transfer from presynaptic neuron to postsynaptic neuron
• There are two basic types of synapses depending on how neurons communicate, electrical and chemical (majority)
• Electrical synapses have cell membranes that converge 2 nm apart with gap junctions of protein channels, permits impulse with rapid transmission
• Chemical synapses have about 20 nm synaptic clefts
• There is jumping of no electrical response as an electrical signal need converted into chemical
• Neurotransmitters (messengers) conduct signal across the synapse binding to chemically activated ion channels opening or closing allowing changed membrane permeability

Neurotransmitters

• Chemical messengers (NTs) used to send signals
• Acetylcholine (low-molecular weight) is released from motor neurons triggering muscle, released by CNS and ANS which uses cholinergic neurons, or inhibitory for cardiac muscle
• Biogenic amines affect mood with concentration imbalance
  • Norepinephrine has adrenergic neurons
  • dopamine
  • serotonin helps regulate food intake
• Amino acids
  • glutamate is excitatory in the brain and is mental mind altering receptor
  • aspartate facilitates learning and memory
  • glycine and gamma-aminobutyric acid (GABA) inhibit neurons of the brain and spinal cord.
• Neuropolypeptides consist of endorphins and enkephalins for endogenous opiods
• Gaseous NTS include retrograde messenger nitric oxide (NO) and carbon monoxide
• NTs are stored in synaptic vesicles, voltage-gated Ca+ channels open for action potential
• Calcium ions flowing through the extracellular fluid combine with presynaptic membrane releasing neurotransmitters in the cleft
• Neurotransmitter receptors >> chemically activated
• Ligand binds with receptor opening the ion channel
• Excess neurotransmitters in synaptic cleft need removal to the postsynaptic neuron to repolarize quickly
• Some are inactivated by enzymes like acetylcholine degrading acetylcholinesterase; biogenic amines are repackaged to the synaptic terminals for reuptake; and several drugs inhibit the reuptake

Synaptic Signals & Potentials

• Activated postsynaptic neuron's receptors can send signal for either to excite or inhibit depending on receptor types like acetylcholine for skeletal muscles
• When neurotransmitters molecules open channels, the activated receptor directly or indirectly binds to receptors
• Calcium ions enter terminal, synaptic vesicles release neurotransmitters, which diffuse through the cleft, ion channels open, and cause depolarization or hyperpolarization
• In excitatory postsynaptic, an EPSP occurs which depolarizes postsynaptic cell, which is a neurotransmitter molecule encapsulated inside the synaptic releases causes ligand binding channels and membrane to open brining the neuron close to firing; unlike the grades response of action potentials (all or none)
• In inhibitory postsynaptic that hyperpolarizes the PSP, IPSPS move away from it's firing levels
• The receptors channels dependent is related to the release or interactions that happen
• Neural integration sums all inputs, with a large % synaptic connections and cell output is related to the integration
• Produced EPSPs occur on the neurons allowing cancel to effects to occur with the graded all or noone

Summation and Neural Circuits

• Each EPSP or IPSP is a graded membrane magnitude depending on the strength of its stimuli
• Temporal summation occurs as repeated stimuli will cause new EPSPs to happen when the ones that happen before decay before the action occurs
• Spatial summation describes several spaced terminals to stimulates when the neurotransmitter occurs stimulating several places
• Neurons form separate networks
• Arrangement in neural circuits is in convergence with input from other neurons
• Neural output diverged is one neuron diverges to innervate several other neurons
• Reverberating circuits depend on feedback when impulses are generated until the synapses decline
• Circuit can depend or depend on themselves
• Regulated y interneurons
• Responsible for rhythms of alertness or memory