It is important to understand concentration gradient (diffusion) & eletrostatic pressure
 

I. Resting potential: At rest the neuron is like a tiny battery with a resting
   potential of about-70 millivolts
 1. selectively permeable membrane:

 2. the fluid both inside and outside of the axon contains ions.
  A. organic anions (A-): trapped inside the cell at all times.
  B. sodium (Na+): Na+ stays primarily on the outside of the cell
     a. voltage gated channel exist for Na+
  C. potassium (K+): these cross the cell membrane more easily & are found mostly inside
      the cell.
     a. voltage gated channels exist for K+
  D. Chloride anions (Cl-) are concentrated mostly outside of the cell.
    a. voltage gated ion channels exist for Cl-
    b. Cl- does not contribute to the resting potential
  E. calcium (Ca+) concentrated mostly outside the neuron
    a. voltage gated ion channels exist for Ca+
 

II. Action potential (firing of a neuron): the ion exchange
  1. voltage dependent Na+ channels in the cell membrane open
  2. Na+ entering causes the cell internal environment to become depolarized
  3. drop in voltage causes K+ channels to open and K+ to pour out of the cell.
  4. The Na+ channels then close but K+ con’t to pour out
  5. this causes the  membrane potential to begin to drop
  6. The ions then diffuse away from the membrane

 
III. Action potential (AP): definition & other facts
1. action potential: is a brief change in the neuron's electrical charge.
2. certain drugs like Novocain inhibit action potentials
3. they are all or none:
4. The AP skips from one node of Ranvier to another
5. APs cause the release of chemicals from terminal buttons (Kingsley p.109)
  A. Neurotransmitters: influence cells located a very short distance away.
  B. neuromodulators: (paracrine) travel further
  C. Hormones: absorbed into the blood, and travel thru the blood stream.
 

IV. Refractory period
 1. absolute refractory period: no stimulus will elicit an action potential
 2. relative refractory period: stronger stimulus is necessary
 

V. sodium-potassium pump: push the Na+ back out & K+ back in.
 

VI. the synapse or synaptic cleft: space between the terminal buttons and the
      membrane of another cell.
  1. synaptic cleft is about 200 A wide (1 ten millionth of a millimeter).

 
VII. neurotransmitter (NT) storage
 1. Synaptic vesicles (SV): are small round pockets that contain NT
   A. formed by invaginations of synaptic bouton
 2. secretory vesicles: membrane bound pockets that contain peptides
   A. these vesicles come from the Golgi apparatus
 

VIII. synaptic transmission (referring to synaptic vesicles (SV))

Presynaptic neuron: (Kingsley p. 112, 113, 114)
 1. APs cause SV to migrate to the presynaptic membrane (docking process),
 2. Ca+ channels open when depolarized by an action potential.
 3. calcium causes SV membrane to fuse with the presynaptic membrane
   A. NT then pours into the synapse..
   B. SV membrane is then pinched off (pinocytosis) & recycled
 
postsynaptic neuron:
 1. NT attach to parts of the postsynapse (i.e., receptors)
   A. The ligand fits into a binding site like a key fits into a lock.
 2. Ligand binding causes ion channels to open.  2 types of receptors exist (Kingsley p. 117)
  A. ionotropic receptors (ligang gated):
  B. metabotropic receptors (G-protein linked)
 

IX. Postsynaptic potentials:
 1. types (EPSPs & IPSPs)
   A. Excitatory postsynaptic potential (EPSP) are depolarizations that make
       The postsynaptic neuron more likely to fire
   B. Inhibitory postsynaptic potentials (IPSP)  are caused by hyperpolarization and inhibit APs.

 2. Postsynaptic potentials (PSPs): other facts (Kingsley p. 122, 123, & 124)
   A. EPSPs and IPSPs are additive
    a. temporal summation & spatial summation.
   B. PSPs: are variable
   C. Threshold: sufficient EPSPs to raise the membrane potential above a
        certain level at the initial segment of the axon, is so an AP will occur
   D. proximal inhibitory synapses have a greater influence (Kingsley p.125)
 
 3. How do postsynaptic potentials occur?
  A. Some NT are exclusively inhibitory others excitatory
  B. most NT can produce either effect depending on the receptor.

4. Types of ligand dependent channels
  A. NT causes ligand gated ion channels to open
  B. There are 4 primary types of NT (ligand) dependent ion channels
    a. Na+ channels:
    b. K+ channels:
    c. Cl- channels:
    d. Ca+ channels:

 
X. How is the NT signal regulated?
 1. NT signals must be terminated
   A. Reuptake: where NT is taken back into the presynaptic cell.
   B. Enzymatic deactivation refers to the breakdown of NT
   C. NT also diffuses out of the synapse
 
2.Autoreceptors: are found on the presynaptic neuron and are thought to regulate internal
   processes
 
3. axoaxonic synapse: These alter the amount of NT released by the terminal
     button.  (Called presynaptic inhibition p. 126 Kingsley)
  A. They usually are inhibitory.
 

__________________________________________________________

I. drugs can influence NT in many ways
 1. synthesis & storage of NT
 2. release of NT into the synapse
 3. binding of NT to receptors of other neurons
 4. inactivation by enzyme degradation & reuptake
 

II. agonist vs antagonist
 1. An agonist: is a chemical (drug or poison) that mimics or facilitates a NT
 2.An antagonist: is a chemical (drug or poison) that opposes the action of NT
 

I. Acetylcholine (ACh)
 1. this NT has 2 types of receptors
   A. nicotinic receptors:
      a. agonist: is nicotine
      b. antagonist: is curare
   B. muscarinic receptors:
      a. agonist: is muscarine
      b. antagonist: in atropine (deadly nightshade

2. deactivated by acetylcholinesterase  (AChE) & choline is reused

3. physostigmine: inhibits AChE (agonist) but is reversible.

4. botulinum toxin prevents the release of ACH from the terminal button (antagonist)
 
5. black widow spider venom causes ACH terminals to release ACH (agonist)
 
 

Monoamines

All monoamines work thru metabotropic receptors

Monoamine oxidase (MAO) & catechol-O-methyltransferase (COMT) deactivate these.
  1. The drug reserpine prevents the storage of the monoamines
 

types of monoamines:

I. Indolamines:

1. Serotonin (5-HT)
  A. produced in the raphe nuclei in the midline of the pons & medulla (p. 133 Kingsley)
  B. the drug parachlorophenylalanine (PCPA) blocks tryptophan hydroxylase & prevents the
      synthesis of 5-HT (an antagonist)
  C. iproniazid block MAO (agonists)
 

II. Catecholamines:

The amino acid tyrosine is the precursor
NT is released thru axononal varicosities: swellings on the axon

1. Norepinephrine (NE) noradrenalin
 A. in the CNS this is produced in the locus ceruleus (nucleus in midbrain) &
      is distributed though out the CNS (p. 132 Kingsley)
 
2. Epinephrine (E) adrenaline
 A. works at the same receptors as NE
 B. stimulates the sympathetic nervous system
 C. ephedrine: alpha & beta receptor agonist
 D. propranolol: beta receptor blocker has antihypertensive effects

3 Dopamine (DA)
 A. produced in substantia nigra & ventral tegmental area (midbrain) & sent to
      the cortex, limbic system, hypothalamus, & basal ganglia (p. 132 of Kingsley)
 B. implicated in movement disorders  e.g., in Parkinson's disease (L-DOPA)
 C. cocaine and amphetamine work by preventing reuptake
 D. apomorphine: stimulates only autoreceptors (an antagonist)
 

Amino Acid Transmitters:
I. gamma aminobutyric acid (GABA)
 1. is produced from glutamic acid (glutamate)
 2. an inhibitory neurotransmitter
 

II. glutamic acid (glutamate):
 1. the principal excitatory NT in the brain
 2. phencyclidine (PCP) may have its effects by influencing this NT
 

III. glycine:
 1. an inhibitory NT found in the brain stem & spinal cord
 2. tetanus bacteria blocks the activity of this NT
 
 

Peptide Transmitters:

Peptide Transmitters: some terminal buttons release both classical NT & peptide NT at once,

I. Endorphins (16-30 amino acids) or enkephalins (shorter chains of amino
    acids).  These are endogenous opiates
 1. 3 types of receptors have been found (mu, kappa, & sigma).
 2. all opiate drugs are endorphin agonists

II. anandamides: a natural ligand similar to THC
 1. receptors have been found for these chemicals

III. substance P: increases perceptions of pain
 
 

Soluble gases:
I. Nitric oxide
  1. Kingsley suggest that this gas may be involved in learning
 

_________________________________________________________________

I. early work:
1. In 1949 Hebb proposed that if a synapse repeatedly becomes active at about the same time that the postsynaptic neuron fires, changes will take place in the structure & chemistry of the synapse.
 
II. long-term potentiation (LTP):
 1. what is LTP
   A. refers to an increase in synaptic efficiency after high levels of activity
        in the presynaptic areas (cooperativity)
   B. presynaptic cells & postsynaptic cell must be active together (associativity)
   C. the weaker synapses become stronger

 2. long-term depression (LTD): is the opposite of LTP & thus may be implicated in forgetting

_____________________________________________________________________

II. Eaton-Lambert Syndrome:
 1. defective calcium channels allow less calcium to enter the presynaptic cell after an AP
 2. less NT is released from the terminal button
 

Back to Neurophysiology Outlines

Back to Home Page