Nerve Impulses and Synaptic Transmission

Central Nervous System (CNS)

• Brain and spinal cord of dorsal body cavity

• Integration and control center

  • Interprets sensory input an dictates motor output

Peripheral Nervous System (PNS)

• The portion of nervous system outside CNS

• Consists mainly of nerves that extend from brain and spinal cord

  • Spinal nerves to and from spinal cord

  • Cranial nerves to and from brain

• Walls of gastrointestinal tract also contain neurons called the enteric nervous system

Sensory (afferent) division

Somatic sensory fibers: convey impulses from skin, skeletal muscles, and joints to CNS

Visceral sensory fibers: convey impulses from visceral organs to CNS

Motor (efferent) division

• Transmits impulses from CNS to effectors

  • Muscles and glands

• Two divisions

  • Somatic nervous system

  • Autonomic nervous system

Cells of the Nervous System

Nervous tissue consists of two principal cell types

• Neuroglia (glial cells): small cells that surround and wrap delicate neurons

• Neurons (nerve cells): excitable cells that transmit electrical signals

Neuroglia of the CNS

• astrocytes

• microglial cells

• ependymal cells

• oligodendrocytes

Astrocytes

• Most abundant, versatile, and highly branched of glial cells

• Cling to neurons, synaptic endings, and capillaries

Functions:

• Support and brace neurons

• Play role in exchanges between capillaries and neurons

• Guide migration of young neurons

• Control chemical environment around neurons

• Respond to nerve impulses and neurotransmitters

• Participate in information processing in brain

Microglial Cells

• Small, ovoid cells with thorny processes that touch and monitor neurons

• Migrate toward injured neurons

• Can transform to phagocytize microorganisms and neuronal debris

Ependymal Cells

• Range in shape from squamous to columnar

• May be ciliated

  • Cilia beat to circulate CSF

  • Line the central cavities of the brain and spinal column

  • Form permeable barrier between cerebrospinal fluid (CSF) in cavities and tissue fluid bathing CNS cells

Oligodendrocytes

• Branched cells

• Processes wrap CNS nerve fibers, forming insulating myelin sheaths in thicker nerve fibers

Satellite cells (Neuroglia of PNS)

• Surround neuron cell bodies in PNS

• Function similar to astrocytes of CNS

Schwann cells (neurolemmocytes) (Neuroglia of PNS)

• Surround all peripheral nerve fibers and form myelin sheaths in thicker nerve fibers

  • Similar function as oligodendrocytes

• Vital to regeneration of damaged peripheral nerve fibers

Neurons

• Neurons (nerve cells) are structural units of nervous system

• Large, highly specialized cells that conduct impulses

• All have cell body and one or more processes

Special characteristics

• Extreme longevity (lasts a person’s lifetime)

• Amitotic, with few exceptioins

• High metabolic rate: requires continuous supply of oxygen and glucose

Resting Membrane Potential

Generating a resting membrane potential depends on differences in

1. K and Na concentrations inside and outside cells

2. in the permeability of the plasma membrane to these ions

Generating an Action Potential

Four main steps

1. Resting state: all voltage-gated Na and K channel are closed

• only leakage channels Na and K are open for maintaining the resting membrane potential

• Each Na channel has two voltage-sensitive gates

  • Activation gates: closed at rest; open with depolarization allowing Na to enter cell

  • Inactivation gates: open at rest; block channel once it is open to prevent Na from entering cell

• Each K channel has one voltage-sensitive gate

  • Closed at rest

  • Opens slowly with depolarization

2. Depolarization: voltage-gated Na channels open

• Depolarizing local currents open voltage-gated Na channels and Na rushes into the cell

• Na activation and inactivation gates open

• Na influx causes more depolarization, which opens Na channels more

• As a result, ICF becomes less negative

• At threshold (-55 to -50 mV), positive feedback causes the opening of all Na channels

• Results in large action potential spike

• Membrane polarity jumps to +30 mV

3. Repolarization: Na channels are inactivating and voltage-gated K channels open

• Na channel inactivation gates close

• Membrane permeability Na declines to resting state

• AP spike stopss rising

• Voltage-gated K channels open

• K exits cells down its electrochemical gradient

• Repolarization: membrane returns to resting membrane potential

4. Hyperpolarization: K channels remain open, Na channels reset

• Some K channels remain open, allowing excessive K efflux

• inside of membrane becomes more negative than in resting state

• this causes hyperpolarization of the membrane (slight dip below resting voltage)

• Na channels also begin to reset

Threshold and the All-or-None Phenomenon

• Not all depolarization events produce APs

• For an axon to “fire”, depolarization must reach threshold voltage to trigger AP

  At threshold:

  • Membrane is depolarized by 15 to 20 mV

  • Na permeability increases

  • Na influx exceeds K efflux

  • The positive feedback cycles begins

All-or-none phenomenon: AP either happens completely, or does not happen at all

Neurotransmitter Receptors

Ionotropic: Ion channels

Metabotropic: G protein-coupled, enzymatic cascade

Neurotrnasmitters

• Excitatory

• Inhibitory

Ionotropic Receptors

• Rapid synaptic transmission

• Sensitive to molecules and sometimes, membrane potential

• Mediates significant membrane currents

• Selective for specific ions

Metabotropic receptors

• G - protein coupled receptor

• Structure of metabotropic receptors

• A single polypeptide with 7 transmembrane alpha helix domains

• Neurotransmitters that bind to metabotropic receptors

  • Amines (eg. dopamine, serotonin, noradrenalin)

  • Peptides

  • Amino acids have few metabotropic receptors

G protein linked receptors (neurotransmitter receptors)

• Responses are indirect, complex, slow and often prolonged

• Involves transmembrane protein complexes

• Cause widespread metabolic changes

  Examples

  • Muscarinic ACh receptors

  • Receptors that bind biogenic amines

  • Receptors that bind neuropeptides

  Mechanism:

  • Neurotransmitter binds to G protein-linked receptor, activating G protein

  • Activated G protein controls production of second messengers such as cyclic AMP, cyclic GMP, diacylglycerol or Ca

  • Second messengers can then:

    • Open or close ion channels

    • Activate kinase enzymes

    • Phosphorylate channel proteins

    • Activate genes and induce protein synthesis

G protein-coupled receptors cause the formation of intracellular second messengers

1. Neurotransmitter (1st messenger) binds and activates receptor

2. Receptor activates G protein

3. G protein activates adenylate cyclase

4. Adenylate cyclase converts ATP to cAMP (2nd messenger)

5. cAMP changes membrane permeability by opening or closing ion channels

6. cAMP activates enzymes

7. cAMP activates specific genes

Neurotransmitters

• Neurotransmitters, along with electrical signals, are the language of nervous system

• 50 or more neurotransmitters have been identified

• Classified chemically and functionally

Acetylcholine (ACh)

• first identified and best understood

• Released at neuromuscular junctions

• also used by many ANS neurons and some CNS neurons

• Synthesized from acetic acid and choline by enzyme choline acetyltransferase

• Degraded bu enzyme acetylcholinesterasse (AChE)

Catecholamines (biogenic amines)

Dopamine, norepinephrine (NE) and epinephrine: made from the amino acid tyrosine

Indolamines (biogenic amines)

• Serotonin: made from the amino acid tryptophan

• Histamine: made from the amino acid histidine

• All widely used in brain: play roles in emotional behaviours and biological clock

• Used by some ANS motor neurons, especially NE

• Imbalances are associated with mental illness

Amino Acids

• Amino acids make up all proteins: therefore, it is difficult to prove which are neurotransmitters

• Amino acids that are proven neurotransmitters

  • Glutamate

  • Aspartate

  • Glycine

  • GABA

Peptides (neuropeptides)

Strings of amino acids that have diverse functions

Substance P

Mediator of pain signals

Endorphines (beta endorphin, dynorphin and enkephalins)

Act a natural opiates; reduce pain perception

Gut-brain peptides

Somatostatin and cholecystokinin (CCK) play role in regulating digestion

Glutamatergic receptors

• EGluR=0mV
  • AMPAR and KainateR
  are rapid

• Inital phase of glu EPSP

• 3 types of receptors

  • AMPA

  • Kainate

  • NMDA

• The 3 types can be found at the same synapse

GABAeric receptors

• GABA is responsible for most inhibitory transmission

• Glycine is responsible for non-GABAergic inhibitory transmission

• GABARs bind ethanol, benzodiazepine, barbiturate

• GABA-A: Ionotropic

• GABA-B: Metabotropic

Neural circuit

Pattern of synaptic connections between neuronw

Types of circuits

• diverging

• converging

• reverberating

• parallel after-discharge

Neural plasticity

Strength of a circuit or of pathways within a circuit change when new synapses form and old synapses removed

• The basis of memory and learning

• Peak during childhood and diminishes with age

Diverging circuit

• One input, many outputs

• An amplifying circuit

• Example: A single neuron in the brain can activate 100 or more motor neurons in the spinal cord and thousands of skeletal muscle fibers

Converging circuit

• Many inputs, one output

• A concentrating circuit

• Example: different sensory stimuli can all elicit the same memory

Reverberating circuit

• Signal travels through a chain of neurons, each feeding back to previous neurons

• An oscillating circuit

• Controls thythmic activity

• Example: involved in breathing, sleep-wake cycles and repetitive motor activities such as walking

Parallel after-discharge circuit

• Signal stimulates neurons arranged in parallel arrays that eventually converge on a single output cell

• Impulses reach output cell at different times, causing a burst of impulses called an after-dischagre

• Example: May be involved in exacting mental processes such as math calculations