1. INTRODUCTION TO NEUROBIOLOGY
LECTURE 9
CH 7
THE NERVOUS SYSTEM: NEURONS AND SYNAPSES

2. Students must review the beginning of Chapter 7 on their own.
See Intro to Neurobiology “A” lecture for assistance; there may be questions on this section on the exams.
This lecture begins with “Electrical Activity in Axons” Section 7.2 (but you are required to know 7.1, which is Anatomy).

3. Fig. 7.11 - Observing Depolarization and Hyperpolarization
Oscilloscope
Measures the potential difference
- 70 mV = resting (neuron), polarized
Depolarization = + charge moves in (excitatory)
Hyperpolarization = neg. charge moves in. (inhibitory)
Repolarization = return to resting.
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4. Gated channels – gates open or close in response to stimuli.
Ion Gating in Axons
Gated channels – gates open or close in response to stimuli.
Closing step 1) ball and chain, step 2) fully closed. K+ Channels can be voltage- gated or non-gated. Na+ Channels are always voltage-gated

5. Depolarization of an Axon

6. All-or-None Law

7. RECRUITMENT – more and more axons become activated
Coding for Stimulus Intensity: the code is not amplitude; the code is frequency!
Different axons will be stimulated at different stimulus intensities. A weak stimulus will activate only those few axons with low thresholds, whereas stronger stimuli can activate axons with higher thresholds.
Note the threshold increase. A heavier weight activates axons with higher thresholds
RECRUITMENT – more and more axons become activated

8. Refractory Period: time when axon is not responsive to a 2nd stimulus
The absolute refractory period occurs during the action potential. Na+ channels are inactive (not just closed). Relative refractory period can be overcome by a strong stimulus. (while K+ diffuses outward). Each action potential remains a separate, all-or-none event.

9. Cable Properties of Neurons
--The ability of neurons to conduct charges through their cytoplasm --Poor due to internal resistance -- and charge leaks out

10. Conduction of Nerve Impulses
When an action potential occurs at a given point on a neuron membrane, voltage- gated Na+ channels open as a wave down the length of the axon.
The action potential at one location serves as the depolarization stimulus for the next region of the axon

11. Saltatory Conduction in a Myelinated Neuron
In an unmyelinated axon, potentials are produced down the entire length of the axon at every patch of membrane.
The conduction rate is slow because so many action potentials are generated, each one, an individual event.
The amplitude of each action potential is the same – conducted without decrement Thin, unmyelinated neuron speed 1.0m/sec
Thick, myelinated neuron speed 100m/sec
Myelin provides insulation, improving the speed of action potential. Nodes of Ranvier allow Na+ and K+ to cross the membrane every 1−2 mm. Na+ ion channels are concentrated at the nodes. Action potentials “leap” from node to node.

12. Otto Loewi (1921)
CHEMICAL SYNAPSES
Discovered Vagusstoff, a chemical secreted by the vagus nerve (acetylcholine).
EXPERIMENT:

13. Acetylcholine (ACh)
ACh is a neurotransmitter that directly opens ion channels when it binds to its receptor.
In some cases, ACh is excitatory, and in other cases it is inhibitory, depending on the organ involved
Excitatory in some areas of the CNS, in some autonomic motor neurons, and in all somatic motor neurons
Inhibitory in some autonomic motor neurons

14. GAP JUNCTIONS: Electrical Synapses
Electrical synapses occur in smooth muscle and cardiac muscle, between some neurons of the brain, and between glial cells.
Stimulation causes phosphorylation or dephosphorylation of connexin proteins to open or close the channels

15. Chemical Synapses
Vesicles are produced in the Golgi and stored at the end of an axon (terminal boutons) The synaptic cleft is very small, 10nm, and the presynaptic and postsynaptic cells are held close together by cell adhesion molecules (CAMs).

16. The Synapse
A synapse is the functional connection between a neuron and the cell it is signaling
In the CNS, this second cell will be another neuron.
In the PNS, the second cell will be in a muscle or gland; often called myoneural or neuromuscular junctions

17. Release of Neurotransmitter
Docking involves a SNARE complex of proteins that bridge the vesicle membrane and the plasma membrane. The SNARE proteins include one in the vesicle membrane (synaptobrevin-2) and two anchored in the plasma membrane (syntaxin and SNAP-25). When an action potential arrives at the presynaptic axon terminal, depolarization opens the Ca+2 channels. When Ca2+ enters the cell, it binds to a protein called synaptotagmin that serves as a Ca2+ sensor
Vesicles containing neurotransmitter are docked at the plasma membrane by three SNARE proteins.
The Ca2+ synaptotagmin complex displaces part of SNARE, and the vesicle fuses.
Forms a pore to release the NT
Neurotransmitter diffuses across the synapse, where it binds to a specific receptor protein.
The neurotransmitter is referred to as the ligand.
This results in the opening of chemically regulated ion channels (also called ligand-gated ion channels).
The neurotransmitter (ligand) binds to a receptor in the postsynaptic membrane

18. Summary of Neurotransmitter Action

19. Graded nature of EPSPs

20. Two Types of Acetylcholine (Cholinergic) Receptors
Nicotinic ACh receptors
Can be stimulated by nicotine Found on the motor end plate of skeletal muscle cells, in autonomic ganglia, and in some parts of the CNS
Muscarinic ACh receptors
Can be stimulated by muscarine (from poisonous mushrooms)
Found in CNS and plasma membrane of smooth and cardiac muscles and glands innervated by autonomic motor neurons

21. BINDING OF ACETYLCHOLINE (LIGAND) TO ITS RECEPTOR
ACETYLCHOLINE CAN BIND TO ITS RECEPTOR, WHICH IS ALSO AN ION CHANNEL
Notice that 2 acetylcholines must bind

22. MUSCARINIC Ach Receptors Require G-Proteins
In the heart, K+ channels are opened by the beta-gamma complex, creating IPSPs (hyperpolarization) that slow the heart rate.
In the smooth muscles of the stomach, K+ channels are closed by the alpha subunit, producing EPSPs (depolarization) and the contraction of these muscles.
Binding of acetylcholine opens K+ channels in some tissues (IPSP) or closes K+ channels in others (EPSP).
Heart: K+ channels open, creating IPSPs  heart rate slowed
Smooth muscle: K+ channels close, creating EPSPs  smooth muscles contract

23. Discovery and analysis of G proteins
MUSCARINIC Ach Receptors Require G-Proteins
Discovery and analysis of G proteins
1994 – Nobel Prize in Physiology or Medicine: Gilman and Rodbell
2012 – Nobel Prize in Chemistry

24. Agonists and Antagonists
Agonists: drugs that can stimulate a receptor
Nicotine for nicotinic ACh receptors
Muscarine for muscarinic ACh receptors
Antagonists: drugs that inhibit a receptor
Atropine from plants, is an antagonist for muscarinic receptors.
Curare (from plants) is an antagonist for nicotinic receptors. Clinically, curare is used as a muscle relaxant. Lethal in high doses; poison dart use.

25. Acetylcholinesterase (AChE)
AChE - enzyme that inactivates ACh activity shortly after it binds to the receptor.
Hydrolyzes ACh into acetate and choline, which are taken back into presynaptic cell for reuse.

26. Action of Acetylcholinesterase (AChE)