12 - The Nervous System

Postsynaptic Potentials

• Neurotransmitter receptors cause graded potentials that vary in strength with

  • Amount of neurotransmitter released

  • Time neurotransmitter stays in area

Types of postsynaptic potentials

1. EPSP—excitatory postsynaptic potentials

2. IPSP—inhibitory postsynaptic potentials

Excitatory Synapses and EPSPs

• Neurotransmitter binding opens chemically gated channels

  • Allows simultaneous flow of Na+ and K+ in opposite directions

• Na+ influx greater than K+ efflux → net depolarization called EPSP (not AP)

• EPSP help trigger AP if EPSP is of threshold strength

  • Can spread to axon hillock, trigger opening of voltage-gated channels, and cause AP to be generated

EPSP

a local depolarization of the postsynaptic membrane that brings the neuron closer to AP threshold. Neurotransmitter binding opens chemically gated ion channels, allowing Na+ and K+ to pass through simultaneously.

Inhibitory Synapses and IPSPs

• Reduces postsynaptic neuron's ability to produce an action potential

  • Makes membrane more permeable to K+ or Cl

    • If K+ channels open, it moves out of cell

    • If Cl- channels open, it moves into cell

  • Therefore neurotransmitter hyperpolarizes cell

    • Inner surface of membrane becomes more negative…hyperpolarized state

    • AP less likely to be generated

IPSP

local hyperpolarization of the postsynaptic membrane that drives the neuron away from AP threshold. Neurotransmitter binding opens K+ or Cl– channels

Summation

• Synaptic Integration

• A single EPSP cannot induce an AP

• EPSPs can summate to influence postsynaptic neuron

• IPSPs can also summate

• Most neurons receive both excitatory and inhibitory inputs from thousands of other neurons

  • Only if EPSP's predominate and bring to threshold→ AP

A single neuron can receive inputs from

thousands of other neurons and form synapses with thousands of other cells

• Figure shows a single motor neuron and the nerve terminals that make synapses with it

Types of Summation

1. temporal summation

2. spatial summation

Temporal summation

One or more presynaptic neurons transmit impulses in rapid-fire order

Spatial summation

Postsynaptic neuron stimulated simultaneously by large number of terminals at same time

Grade potentials vs Action Potential

• Grade Potential

  • take place cell body and dendrite

  • short distance

  • various magnitudes (drop off as get further)

  • summate

  • chemically gated channels

• Action Potential

  • start in axon hillock and proceed down axon

  • long distance

  • all or none

  • do not summate

  • voltage gated channels

Synaptic Potentiation

• integration

• Repeated use of synapse increases ability of presynaptic cell to excite postsynaptic neuron

  • Ca2+ concentration increases in presynaptic terminal and postsynaptic neuron

• Brief high-frequency stimulation partially depolarizes postsynaptic neuron

  • Chemically gated channels (NMDA receptors) allow Ca2+ entry

  • Ca2+ activates kinase enzymes that promote more effective responses to subsequent stimuli

Presynaptic Inhibition

• Excitatory neurotransmitter release by one neuron inhibited by another neuron via an axoaxonal synapse

• Less neurotransmitter released

• Smaller EPSPs formed

Types of Synaptic Integration

1. Summation

2. Synaptic Potentiation

3. Presynaptic Inhibition

Neurotransmitters

• Language of nervous system

• 100 neurotransmitters have been identified

  • Most neurons make two or more neurotransmitters

• Neurons can exert several influences

• Usually released at different stimulation frequencies

Classification of neurotransmitters

• chemical structure

• function

  • Effects – excitatory versus inhibitory

  • Actions – direct versus indirect

Chemical structure classification of neurotransmitters

1. Acetylcholine

   1. Nicotinic vs muscarinic receptors

2. Biogenic amines

   1. Catecholamines

   2. Indolamines

3. Amino acids

   1. Glutamate

   2. Aspartate

   3. Glycine

   4. GABA

4. Peptides - Neuropeptides

   1. Substance P

   2. Endorphins

   3. Gut-brain peptides

5. Purines

   1. ATP

   2. Adenosine

6. Gases and lipids - gasotransmitters

   1. Nitric Oxide

   2. Carbon Monoxide

   3. Hydrogen sulfide gases

7. Endocannabinoids

Direct action

• Neurotransmitter binds to and opens ion channels

• Promotes rapid responses by altering membrane potential

• Examples: ACh and amino acids

Indirect action

• Neurotransmitter acts through intracellular second messengers, usually G protein pathways

• Broader, longer-lasting effects similar to hormones

• Biogenic amines, neuropeptides, and dissolved gases

Neurotransmitter receptors types

1. Channel-linked receptors

   1. Mediate fast synaptic transmission

2. G protein-linked receptor

   1. Oversee slow synaptic responses

General mechanism of the origin and termination of neurotransmission (diagram)

Mechanism of vesicle fusion and recycling (diagram)

Acetylcholine

• ACh

• First identified; best understood

• Released at neuromuscular junctions, by some ANS neurons, by some CNS neurons

• Synthesized from acetic acid and choline by enzyme choline acetyltransferase

• Degraded by enzyme acetylcholinesterase (AChE)

• Bind to

  • Nicotinic receptors (ion channels, fast, sympathetic and parasympathetic nervous system)

  • muscarinic receptors (G-protein coupled receptors, slow, parasympathetic nervous system – rest and digest)

_ nerves secrete ACh

Cholinergic

Nicotinic receptors

• ion channels, fast, sympathetic and parasympathetic nervous system

• get their name from nicotine

  • Nicotine selectively binds to the nicotinic receptors

• are all excitatory

muscarinic acetylcholine receptors

• G-protein coupled receptors, slow, parasympathetic nervous system – rest and digest

• gets their name from a chemical that selectively attaches to that receptor muscarine

  • Muscarine is a natural product found in certain mushrooms

• can be both excitatory and inhibitory depending of the subtype

Biogenic amines

• Broadly distributed in brain

  • Play roles in emotional behaviors and biological clock

• Some ANS motor neurons (especially NE)

• Imbalances associated with mental illness

1. Catecholamines

2. Indolamines

Catecholamines

• type of  Biogenic amines

• Dopamine, norepinephrine (NE), and epinephrine

• Synthesized from amino acid tyrosine

• Adrenergic or “working on adrenaline” nerve cells

Indolamines

• type of Biogenic amines

• Serotonin and histamine

• Serotonin synthesized from amino acid tryptophan; histamine synthesized from amino acid histidine

Dopamine receptors and degradation

Adrenergic receptors

target catecholamines, especially norepinephrine (noradrenaline) and epinephrine (adrenaline)

Serotonin receptors

Amino acid Neurotransmitters

1. Glutamate - excitatory

2. Aspartate

3. Glycine

4. GABA—gamma (γ)-aminobutyric acid - inhibitory

neuropeptides

1. Substance P

   1. Mediator of pain signals

2. Endorphins

   1. Beta endorphin, dynorphin and enkephalins

   2. Act as natural opiates; reduce pain perception

3. Gut-brain peptides

   1. Somatostatin and cholecystokinin

Purines as Neurotransmitters

• ATP!

• Adenosine

  • Potent inhibitor in brain

  • Caffeine blocks adenosine receptors

• Act in both CNS and PNS

• Produce fast or slow responses

• Induce Ca2+ influx in astrocytes

gasotransmitters

• gases and lipids

• Nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide gases (H2S)

• Bind with G protein–coupled receptors in the brain

• Lipid soluble

  • easily get into membrane

• Synthesized on demand

• NO involved in learning and formation of new memories; brain damage in stroke patients, smooth muscle relaxation in intestine

• H₂S acts directly on ion channels to alter function

Endocannabinoids

• Act at same receptors as THC (active ingredient in marijuana)

  • Most common G protein-linked receptors in brain

• Lipid soluble

• Synthesized on demand

• Believed to be involved in learning and memory

• May be involved in neuronal development, controlling appetite, and suppressing nause

Classification of Neurotransmitters: Function

• Great diversity of functions

• Can classify by

  • Effects – excitatory versus inhibitory

  • Actions – direct versus indirect

Classification of Neurotransmitters: Effects

• excitatory versus inhibitory

  • based on receptor present

• Neurotransmitter effects can be excitatory (depolarizing) and/or inhibitory (hyperpolarizing)

• Effect determined by receptor to which it binds

  • GABA and glycine usually inhibitory

  • Glutamate usually excitatory

  • Acetylcholine and NE bind to at least two receptor types with opposite effects

    • ACh excitatory at neuromuscular junctions in skeletal muscle

    • ACh inhibitory in cardiac muscle

Ionotropic Mechanism of Action

• Channel-Linked (Ionotropic) Receptors

• Ligand-gated ion channels

• Action is immediate and brief

• Excitatory receptors are channels for small cations

  • Na+ influx contributes most to depolarization

• Inhibitory receptors allow Cl– influx that causes hyperpolarization

Metabotropic Mechanism of Action

• G Protein-Linked Receptors

• Responses are indirect, complex, slow, and often prolonged

• Transmembrane protein complexes

• Cause widespread metabolic changes

• Examples: muscarinic ACh receptors, receptors that bind biogenic amines and neuropeptides

G Protein-Linked Receptors: Mechanism Steps

• Neurotransmitter binds to G protein–linked receptor

• G protein is activated

• Activated G protein controls production of second messengers, e.g., Cyclic AMP, cyclic GMP, diacylglycerol, or Ca²⁺

• Second messengers

  • Open or close ion channels

  • Activate kinase enzymes

  • Phosphorylate channel proteins

  • Activate genes and induce protein synthesis