A junction that mediates information transfer from one neuron:

1
Synapses

• A junction that mediates information transfer
  from one neuron
• To another neuron
• To an effector cell
• Presynaptic neuron conducts impulses toward the
  synapse
• Postsynaptic neuron transmits impulses away
  from the synapse

2
The Synapse

• Junction between two cells
• Site where action potentials in one cell cause
  action potentials in another cell
• Types of cells in synapse
• Presynaptic
• Postsynaptic

3
Synapses

• Axodendritic synapse
• Axosomatic synapse
• Axoaxonic synapse

Figure 11.17
4
Electrical Synapses

• Gap junctions that allow local current to flow
  between adjacent cells. Connexons protein tubes
  in cell membrane.
• Found in cardiac muscle and many types of smooth
  muscle. Action potential of one cell causes
  action potential in next cell, almost as if the
  tissue were one cell.
• Important where contractile activity among a
  group of cells important.

5
Chemical Synapses

• Components
• Presynaptic terminal
• Synaptic cleft
• Postsynaptic membrane
• Neurotransmitters released by action potentials
  in presynaptic terminal
• Synaptic vesicles action potential causes Ca 2
  to enter cell that causes neurotransmitter to be
  released from vesicles
• Diffusion of neurotransmitter across synapse
• Postsynaptic membrane when ACh binds to
  receptor, ligand-gated Na channels open. If
  enough Na diffuses into postsynaptic cell, it
  fires.

6
Chemical Synapse

• Events at a chemical synapse
• 1. Arrival of nerve impulse opens
• volage-gated calcium channels.
• 2. Ca influx into presynaptic term.
• 3. Ca acts as intracellular messenger
• stimulating synaptic vesicles to fuse with
• membrane and release NT via exocytosis.
• 4. Ca removed from terminal by
• mitochondria or calcium-pumps.
• 5. NT diffuses across synaptic cleft and
• binds to receptor on postsynaptic memb
• 6. Receptor changes shape of ion channel
• opening it and changing membrane potential
• 7. NT is quickly destroyed by enzymes or
• taken back up by astrocytes or presynaptic
• membrane.
• Note For each nerve impulse reaching the
  presynaptic terminal, about 300 vesicles are
  emptied into the cleft.

7
Neurotransmitter Removal

• Method depends on neurotransmitter/synapse.
• ACh acetylcholinesterase splits ACh into acetic
  acid and choline. Choline recycled within
  presynaptic neuron.
• Norepinephrine recycled within presynaptic
  neuron or diffuses away from synapse. Enzyme
  monoamine oxidase (MAO). Absorbed into
  circulation, broken down in liver.

8
Removal of Neurotransmitter from Synaptic Cleft
9
Receptor Molecules and Neurotransmitters

• Neurotransmitter only "fits" in one receptor.
• Not all cells have receptors.
• Neurotransmitters are excitatory in some cells
  and inhibitory in others.
• Some neurotransmitters (norepinephrine) attach to
  the presynaptic terminal as well as postsynaptic
  and then inhibit the release of more
  neurotransmitter.

10
Neurotransmitters

• Chemicals used for neuronal communication with
  the body and the brain
• 50 different neurotransmitters have been
  identified
• Classified chemically and functionally
• Chemically
• ACh, Biogenic amines, Peptides
• Functionally
• Excitatory or inhibitory
• Direct/Ionotropic (open ion channels) or
  Indirect/metabotropic (activate G-proteins) that
  create a metabolic change in cell

11
Chemical Neurotransmitters

• Acetylcholine (ACh)
• Biogenic amines
• Amino acids
• Peptides
• Novel messengers ATP and dissolved gases NO and
  CO

12
Neurotransmitters Acetylcholine

• First neurotransmitter identified, and best
  understood
• Released at the neuromuscular junction
• Synthesized and enclosed in synaptic vesicles
• Degraded by the enzyme acetylcholinesterase
  (AChE)
• Released by
• All neurons that stimulate skeletal muscle
• Some neurons in the autonomic nervous system
• Binds to cholinergic receptors known as nicotinic
  or muscarinic receptors
• Nicotinic receptors
• Neuromuscular junction of skeletal muscles

13
Cholinergic Receptors

• Nicotinic receptors
• - On neuromuscular junction of skeletal muscle
• - On all ganglionic neurons of autonomic nervous
  system
• - Excitatory
• Muscarinic receptors
• - All parasympathetic target organs (cardiac and
  smooth
• muscle)
• - Exciatory in most cases

14
Acetylcholine

• Effects prolonged (leading to tetanic muscle
  spasms and neural frying) by nerve gas and
  organophosphate insecticides (Malathion).
• ACH receptors destroyed in myasthenia gravis
• Binding to receptors inhibited by curare (a
  muscle paralytic agent-blowdarts in south
  American tribes) and some snake venoms.

15
Neurotransmitters Biogenic Amines

• Include
• Catecholamines dopamine, norepinephrine (NE),
  and epinephrine (EP)
• Indolamines serotonin and histamine
• Broadly distributed in the brain
• Play roles in emotional behaviors and our
  biological clock

16
Synthesis of Catecholamines

• AA tyrosine parent cpd
• Enzymes present in the cell determine length of
  biosynthetic pathway
• Norepinephrine and dopamine are synthesized in
  axonal terminals
• Epinephrine is released by the adrenal medulla as
  a hormone

Figure 11.22
17
BIOGENIC AMINES

• Norepinephrine (aka Noradrenaline)
• Main NT of the sympathetic branch of autonomic
  nervous system
• Binds to adrenergic receptors (? or ? -many
  subtypes, ?1, ?2, etc)
• Excitatory or inhibitory depending on receptor
  type bound
• Feeling good NT
• Release enhanced by amphetamines
• Removal from synapse blocked by antidepressants
  and cocaine
• Dopamine
• Binds to dopaminergic receptors of substantia
  nigra of midbrain and hypothalamus
• Feeling good NT
• Release enhanced by amphetamines
• Reuptake block by cocaine
• Deficient in Parkinsons disease
• May be involved in pathogenesis of
  schizophrenia

18
Serotonin (5-HT)

• Synthesized from a.a. tryptophan
• May play a role in sleep, appetite, and
  regulation of moods
• Drugs that block its uptake relieve anxiety and
  depression
• SSRIs selective serotonin reuptake inhibitors
• Include drugs such as Prozac, Celexa, Lexapro,
  Zoloft

19
Neurotransmitters Amino Acids

• Include
• GABA Gamma (?)-aminobutyric acid
• Glycine
• Aspartate
• Glutamate
• Found only in the CNS

20
Amino Acids

• GABA
• Main inhibitory neurotransmitter in the brain
• Inhibitory effects augmented by alcohol and
  antianxiety drugs like Valium
• Increases influx of Cl- in postsynaptic neuron,
  hyperpola- rising it and thus inhibiting it!
• GLUTAMATE
• Widespread in brain where it represents
  the major
• excitatory neurotransmitter
• Important in learning and memory
• Stroke NT -excessive release produces
  excitotoxicity
• neurons literally stimulated to death most
  commonly
• caused by ischemia due to stroke (Ouch!)
• Aids tumor advance when released by gliomas
  (ouch!)

21
Neurotransmitters Peptides

• Include
• Substance P mediator of pain signals
• Beta endorphin, dynorphin, and enkephalins
• Act as natural opiates, reducing our perception
  of pain
• Found in higher concentrations in marathoners and
  women who have just delivered
• Bind to the same receptors as opiates and
  morphine

22
Neurotransmitters Novel Messengers

• Nitric oxide (NO)
• A short-lived toxic gas diffuses through
  post-synaptic membrane to bind with intracellular
  receptor (guanynyl cyclase)
• Is involved in learning and memory
• Some types of male impotence treated by
  stimulating NO release (Viagra)
• Viagra ? NO release ? cGMP ? smooth muscle
  relaxation ? increased blood flow ? erection
• Cant be taken when other pills to dilate
  coronary b.v. taken
• Carbon monoxide (CO) is a main regulator of cGMP
  in the brain