Synaptic Transmission

Electrical Communication

Direct communication between neurons

Chemical Communication

Communication via chemical messengers

Electrical Synapses

Low-resistance junctions that conduct electrical potentials directly from one cell to another; occur at gap junctions; bi-directional (sometimes uni-directional)

Gap Junctions

Consists of a plaque, or cluster, of membrane-bridging channels (connexons); connexons permit ions and other small polar molecules to pass from one cell to another

Advantages of Electrical Transmission

• Reliable - secure electrical transmission

• Fast - no synaptic delay

• Efficient - one cell activates a group of other cells 

• Tough - not susceptible to other types of poison and drugs 

Synaptic Vesicles (Presynaptic Terminals)

Enclosures that contain chemicals

Secretory Granules (Presynaptic Terminals)

Bigger synaptic vesicles

Synaptic Cleft

Gap between pre- and postsynaptic membrane; releases the chemicals across the gap 

Chemical Transmission

• Synaptic Efficiency: Have excitatory and inhibitory effects on postsynaptic neuron activity

• Integration: Chemical synapses allow better summation of inputs than electrical

• Plasticity: Synapses can be made stronger, never weaker

• Requires a lot of machinery 

Electrical Transmission

• Can’t be excitatory at one location and inhibitory at another

• Little to no plasticity, not very flexible 

Coexistence

Releasing one small neurotransmitter and one large neurotransmitter

Exocytosis

The process of neurotransmitter release packaged in large and small vesicles

1) AP depolarizes the presynaptic membrane via Nav channels

2) Depolarization opens the voltage-gated Ca channels (Cav)

3) Ca enters concentration electrical gradients → further depolarizing

4) Elevation of Ca triggers fusion of vesicles 

Ionotropic Receptors

Exclusively small NTs that open up ion channels; directly open a channel, either cause a net depolarization of the cell by opening a Na+ channel, or bring the polarization up by opening a Cl- channel

Metabotropic Receptors

Associated with signal proteins and gene proteins; membrane protein. NT binding activates G protein that either acts directly on an ion channel, opening it from the inside, or acts on an enzyme that generates a second messenger. 

Metabotropic vs Ionotropic

Metabotropic: Slow, longer-lasting, membrane protein, small and large NTs

Ionotropic: Fast and short-acting, associated with ligand-activated ion channels, small NTs

Autoreceptors

Metabotropic receptors on an axon terminal tell the axon to maintain appropriate levels of neurotransmitter release 

Re-uptake

Free NT directly taken up by terminal, re-packaged into vesciles or enzymatically destroyed

Enzymatic Degradation

Breakdown of NT by enzymes, followed by re-uptake of breakdown products, re-synthesis of NT in nerve terminal (Ach)

Diffusion

NT concentration in cleft declines

Scavenging

Free NT taken up by astrocytes via specialized membrane transporters (amino acid and biogenic amine NTs)

Steps in Synaptic Transmission

1. NTs are synthesized from precursors under the influence of enzymes

2. NTs are stored in vesicles

3. NTs that leak from their vesicles are destroyed by enzymes

4. APs cause vesicles to fuse with the presynaptic membrane and release their NTs into the synapse

5. Released NTs bind with autoreceptors and inhibit subsequent neurotransmitter release

6. Released NTs bind to postsynaptic receptors

7. Released Nts are deactivated by either reuptake or enzymatic degradation

Excitatory Postsynaptic Potentials (EPSP)

Net inward current (depolarizing), increasing probability of reaching AP threshold; some current will flow in → positive charge

Inhibitory Postsynaptic Potentials (IPSP)

Net outward current (hyperpolarizing), decreases likelihood of reaching AP threshold

Shunting

Open channels prevent/reduce depolarization by “clamping'“ V_m near E_ion; don’t see anything happening, blocking mechanism

EPSP Mechanism

Transmitter-gated channel reversal potential is less negative than Vm. When opened, carry net inward cation current (Na+) that depolarizes the membrane 

Nicotinic Acetylcholine (nAchR) Receptors

Dominant EPSP receptor; permeable to cations, both Na+ and K+

Negative Vm = net inward current (depolarizing: I_Na > I_K)

Positive Vm = net outward current (hyperpolarizing: I_K > I_Na)

NDMA Receptor

Transmitter and voltage-gated: glutamate sensitive; non-linear I-V relationship: current flow only begins above threshold to remove Mg²⁺ and unblock the channel, which allows calcium flow for plasticity 

Glutamate Receptors:

Two NT binding sites; permeable to both Na and K

Non-NMDA Receptors

Linear current-voltage relationship (like nAchR)

IPSP Mechanism

NT opens K+ or Cl- channels that carry net outward current; outward current hyperpolarizes the membrane and if Vm is more positive than E_K (-80 mV) or E_Cl (-65 to -70 mV)

Glycine

Small NT IPSP transmitter that predominates in the spinal cord

GABA 

Inhibitory NT that predominates in the cortex

Type A = generates a net Cl- influx, which drives the membrane toward E_Cl

Type B = metabotropic receptors generate a net K+ efflux, which drives the membrane toward E_K

Shunting PSPs

Typically inhibitory, some may be excitatory; tends to happen near or on the soma; Cl- channel lets all the current flow out; Cl currents become dominant over resting currents. CL- influx yields a net outward (+) current, but outward current counteracts depolarizing inward current, blocking excitation

Graded PSP Property

Amplitude: Stronger stimuli = bigger PSPs

• Stronger stimulus → more vesicles → larger PSP 

Rapid PSP Property

EPSPs and IPSPs travel quickly from their receptor to their soma

Decremental PSP Property

They get small as they travel to the soma because dendrites are leaky hoses (not surrounded by myelin)

Duration PSP Property

Depends upon:

• Amount of transmitter in cleft

• Time-course of postsynaptic channel activity

• Time constant of postsynaptic membrane

Synaptic Integration

Summation of all EPSPs and IPSPs, which affects the probability of action potential generation

Summation

PSPs alone will not reach the threshold 

Temporal Summation

Summation of PSPs over time at a single synapse 

Spatial Summation

Summation of PSPs from synapses at different locations on the postsynaptic membrane; length constant is critical