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

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).

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. Click HERE

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

Depolarization of an Axon

All-or-None Law

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

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.

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

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

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.

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

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

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

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

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).

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

Summary of Neurotransmitter Action

7.4 Acetylcholine

Acetylcholine (ACh) THIS IS AN EARLIER SLIDE! ACh is a neurotransmitter that can have different effects on different tissues. In some cases, ACh is excitatory, and in other cases it is inhibitory, depending on the organ involved How does this happen?

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

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

Graded nature of EPSPs

Question? What would happen if a person had a disease that caused a deactivation of nicotinic ACh receptors located in the motor end plates* of skeletal muscle cells? Discuss this with your neighbor. *motor end plates are the part of the muscle cell that is activated by neurons.

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

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.

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

Action of Acetylcholinesterase (AChE)