1. Misericordia University
Neuronal Signaling
General Physiology
Tony Serino. Ph.D.
Biology Dept.
Misericordia University

2. Nervous System Nervous tissue: Generates and conducts electrical
Controls and/or modifies all other systems
Rapid response time
Usually short duration effects
Nervous tissue:
Generates and conducts electrical
Consists of neurons and neuroglia cells

3. Neuron Anatomy Axonal terminal Nerve ending Synaptic boutons
Synaptic knobs

4. Functional Zones of a Neuron
Receptor Zone
Initial segment of Axon (trigger zone)
Nerve endings
Axon

5. Synapses Areas where neurons communicate with other cells
Can be chemical (with neurotransmitters) or electrical (gap junctions)
May be in different shapes

6. Anatomy of Synapse (chemical)
Neurotransmission ends when NT diffuses away,
re-absorbed by presynaptic neuron, or NT metabolized
(degraded) by enzymes in cleft

7. Neurotransmission
Action potential (AP)) descends axon to synaptic terminal
Depolarization opens voltage gated Ca++ channels in presynaptic membrane
Ca++ enters terminal
Triggers a number of synaptic vesicles to fuse with outer membrane which diffuses across cleft
NT binds to receptor on postsynaptic membrane
This leads to channels opening on postsynaptic membrane changing the membrane’s potential; NT is removed from the cleft
A number of vesicles are held in an active zone for secretion by SNARE proteins
Synaptotagmin may play role in linking calcium to vesicle secretion

8. Neurotransmitters
Catecholamines

9. Membrane Potentials Requires:
A difference in ion distribution across membrane
Selectively permeable membrane
Non-diffusible anions
Electrogenic pump

10. Equilibrium Potentials
Voltage necessary to stop the movement of a charged particle down its concentration gradient across a semi-permeable membrane
Can be calculated using the Nernst Equation
Simplifying (filling in constants);

11. Equilibrium Potential
Using the concentration values given; calculate the equilibrium potential for Na+: E ~ +60 mV K+: E ~ -90 mV Cl-: E ~ ?? mV

12. Distribution of Excess Charges
Most of the cytoplasm and extracellular fluid is electrically neutral, only the membrane sees a potential difference
This is measurable in mV
The total effect of ions on the membrane potential is calculable by Goldman’s Equation; where Vm = membrane potential; Px = permeability of membrane to ion

13. Goldman’s Constant Field Equation
PNa = 0.035
PK = 1
PCl = 0.001
Vm = -70 mV
The extremely low chloride permeability and the fact that the membrane is near Cl- equilibrium potential makes its effect on resting membranes negligible. Potassium has by far the greatest influence on the resting membrane potential due to its greater permeability.

14. Gated Channel Proteins
Opening gate allows ions to travel into or out of the cell thereby changing the membrane potential
Can be controlled chemically or electrically

15. Graded Potentials Depolarization Hyperpolarization Transient
Decremental
Most due to chemically gated channels opening
Can be summated
Proportional to stimulus strength
May be excitatory or inhibitory
Depolarization
Inside of cell becomes less negative
Hyperpolarization
Inside of cell becomes more negative

16. Summation Temporal –a single axon fires repeatedly
Spatial –two or more axons fire simultaneously

17. Typical Receptor Zone Activity

18. Action Potentials Wave-like, massive depolarization
Propagated down entire length of axon or muscle cell membrane
All or none
No summation possible
Due to opening of voltage gated channels and corresponding positive feedback cycle established
1. Foot –graded potentials
2. Uplimb –fast depolarization
3. Downlimb –fast repolarization
4. After Hyperpolarization –overshoot due to ion distribution 2 3 1 4

19. Events in Membrane during the AP

20. Refractory Periods Absolute Refractory Period
Relative Refractory Period 20
Uplimb Depolarization Na+ enters
Downlimb (Repolarization; K+ leaves)
Membrane Potential (mV)
Threshold
-55
-70
Stimulus
After-hyperpolarization
Resting Potential
Time (msec)

21. -many NT may simply modify neuronal activity rather than leading to an AP directly
Neuromodulators

22. Synaptic Plasticity
-long term plastic changes that increase or decrease synaptic function based on synaptic history (or experience)
Auto-regulation –modification of firing rate by pre-synaptic neuron sensing degree of activity through monitoring NT in cleft or perceiving some modulator secreted by post-synaptic cell
Pre-synaptic Inhibition or Facilitation –adjustment of firing rate by another neurons activity just prior to synapse
Habituation –exposure to benign stimulus over time decreases pre-synaptic firing
Sensitization –increase responsiveness to a previously habituated stimulus that has been paired with a noxious stimulus
LTP (long term potentiation) – a long-lasting increase in synaptic effectiveness due to prolonged use

23. Glutamate is the most common excitatory NT in CNS
Two ligand gated ion channel receptors found in synapse: AMPA (Na+) and NMDA (Ca++)
Released Glutamate binds to AMPA and triggers EPSP
NMDA receptors require glutamate and a depolarized membrane
Repeated firing of pre-synaptic neuron finally raises the membrane potential enough to open NMDA channel
Ca++ activates second messenger that increase glutamate sensitivity and maybe release
Long Term Potentiation -in glutamate secreting synapses -theory for memory

24. Drug Intervention Possibilities
Increase leakage and breakdown of NT from vesicles
Agonize NT release
Block NT release
Inhibit NT synthesis
Block NT uptake
Block degradative enzymes in cleft
Bind to post-synaptic receptor
Stimulate or inhibit second messengers in post-synaptic cell

25. Axonal Transport
Anterograde –towards synapse; flow of synaptic vesicles, mitochondria, etc.
Retrograde –towards CB; recycled membrane vesicles, neuromodulators, etc.

26. AP propagation in unmyelinated axons
The depolarization event triggers depolarization in the next area of the axon membrane; followed by repolarization. In this way the AP appears to move in a wave-like fashion over an unmyelinated axon membrane.

27. AP propagation in myelinated axons
The AP appears to jump from node to node (saltatory conduction); the myelin sheath eliminates the need to depolarize the entire membrane.

28. Regeneration of Nerve Fibers
Damage to nerve tissue is serious because mature neurons are post-mitotic cells
If the soma of a damaged nerve remains intact, damage may be repaired
Regeneration involves coordinated activity among:
remove debris
form regeneration tube and secrete growth factors
regenerate damaged part

29. Response to Injury
Anterograde degeneration with some retrograde; phagocytic cells (from Schwann cells, microglia or monocytes) remove fragments of axon and myelin sheath
Cell body swells, nucleus moves peripherally
Loss of Nissl substance (chromatolysis)
In the PNS, some Schwann cells remain and form a tubular structure distal to injury; if gap or scarring is not great axon regeneration may occur with growth down tube
In the CNS, glial scar tissue seems to prevent regeneration
If contact with tube is not established then no regeneration and a traumatic neuroma forms

30. Regeneration in PNS