Topic 5 Synaptic Transmission Lange

1. Topic 5 Synaptic Transmission Lange Biology 463 - Neurobiology

2. Introduction Synaptic Transmission • The synapse is the “space” between neurons or neurons and other cells • Information transfer occurs from one neuron to the next at a synapse • Has a significant role in EVERY ACTIVITY of the nervous system

3. Charles Sherrington – recipient of the 1932 Nobel Prize in physiology. Dr. Sherrington was a physiologist and originator of the term “synapse”

4. Otto Loewi – in the 1920s identified that the message transmission between the heart and the vagus nerve was chemical. He initially called this compound “vagussstoff” and it eventually became known as acetylcholine.

5. Edwin Furshpan (left) and David Potter (right) in the 1950s first demonstrated electrical synapses. These were first demonstrated in escape-related giant neurons in crayfish.

6. Properties of Synapses In the synapse, there is a specific direction of information flow • Movement is in one direction: neuron to target cell • The neuron ahead of the synapse is the presynaptic neuron • The neuron after the synapse is called the postsynaptic neuron or sometimes the target neuron

7. Chemical Synapses – at a chemical synapse, one neuron releases a neurotransmitter into a small space (the synapse) that is adjacent to another neuron. • Electrical Synapses - a mechanical and electrically conductive link between two abutting neurons formed at a narrow gap between the pre- and postsynaptic neurons known as a gap junction. • Compared to chemical synapses, electrical synapses conduct nerve impulses faster, but • Unlike chemical synapses electrical synapses do not have “gain” (the signal in the postsynaptic neuron is the same or smaller than that of the originating neuron). • Electrical synapses are often found in neural systems that require the fastest possible response, such as defensive reflexes.

8. The gap junction is the key feature allowing for electrical synapse firing between neurons.

9. Note: Because the gap junction is able to allow ion flow in either direction, the effect is to make electrical synapses BIDIRECTIONAL. This difference means that neural circuits with electrical synapses can perform quite differently than those with chemical synapses. Typically the channel created by the grouping of proteins is called a connexon. However, as shown here, the term connexon can also be applied to the aggregate cluster of proteins.

10. Electrical Synapses can occur in places other than in regions associated with escape behaviors. In this example, electrical synapses are located in the vertebrate brain and it is now know that the entirety of the CNS contains many electrical synapses. It is believed that the electrical synapse is associated with regions/responses that require an especially high degree of synchrony.

11. The Chemical Synapse: • synaptic cleft • presynaptic potential • postsynaptic potential • secretory granules • (dense core vesicles) • synaptic vesicles • receptors • active zone

12. Fast Excitatory Synapse – for example one of the class of nicotinic neurons in the brain. General Synapse in the PNS

13. CNS Synapses • Axodendritic: Axon to dendrite • Axosomatic: Axon to cell body • Axoaxonic: Axon to axon • Dendrodendritic: Dendrite to dendrite

15. CNS Synapses (Specialized Groupings) • Gray’s Type I: asymmetrical postsynaptic membrane (thicker) typically excitatory • Gray’s Type II: symmetrical postsynaptic membrane typically inhibitory

16. Arrow above points to the synapse from the presynaptic side. Gray's Type 2 is synonymous with the term Symmetric Synapse. Arrow above points to the synapse from the presynaptic side. Gray's Type 1 is synonymous with the term Asymmetric Synapse.

17. The Neuromuscular Junction (NMJ) • the post synaptic membrane at a muscle cell or group • this post synaptic membrane is called a motor end plate • THOUGHT QUESTION: • These NMJ’s have been widely studied for many decades and have been used to understand general mechanisms of many neural junctions (aka synapses). Why do you think this is so?

19. Steps Seen in Chemical Synaptic Transmission • Neurotransmitter synthesis • Loading of neurotransmitter into synaptic vesicles • Vesicles fuse with SNARE pins to presynaptic terminal • Neurotransmitter spills into synaptic cleft via exocytosis • Neurotransmitter binds to postsynaptic receptor proteins • Biochemical “electrical” message elicited in postsynaptic cell • Removal/retrieval of neurotransmitter from synaptic cleft

20. Major Neurotransmitter Groups Amino acids: small organic molecules that we know are the building blocks of proteins • Glutamate - considered to be the major mediator of excitatory signals in the mammalian central nervous system and is involved in most aspects of normal brain function including cognition, memory and learning. • Glycine - Glycine is an inhibitory neurotransmitter in the central nervous system, especially in the spinal cord, brainstem, and retina. • GABA – (γ-Aminobutyric acid) is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays a role in regulating neuronal excitability throughout the nervous system. In humans, GABA is also directly responsible for the regulation of muscle tone.

21. Amines: organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia. • Dopamine - a catecholamine neurotransmitter present in a wide variety of animals. In the brain, dopamine is involved in activating five different types of dopamine receptors—D1, D2, D3, D4, and D5. • Acetylcholine - in the PNS, acetylcholine activates muscles, and is a major neurotransmitter in the autonomic nervous system. In the CNS, acetylcholine and the associated neurons form a neurotransmitter system, the cholinergic system, which tends to cause “anti-excitatory” actions • Histamine - cell bodies of histaminergics, the neurons which release histamine, are found in the posterior hypothalamus. Histaminergic action is known to modulate sleep. Classically, antihistamines (H1 histamine receptor antagonists) produce sleep.

22. Peptides: Short amino acid chains (i.e. proteins) stored in and released from secretory granules. • Dynorphin - produced in many different parts of the brain, including the hypothalamus, and the spinal cord. Dynorphin has many different physiological actions, depending upon its site of production. • dynorphin that is made in magnocellular vasopressin neurons of the supraoptic nucleus is important in the patterning of electrical activity • Dynorphin produced in the arcuate nucleus and in orexin neurons of the lateral hypothalamus affects the control of appetite. • Enkephalins - involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, or specifically endorphins

24. Principles of Chemical Synaptic Transmission Neurotransmitter Release • Exocytosis: Process by which vesicles release their contents • Mechanisms • Process of exocytosis stimulated by release of intracellular calcium, [Ca2+] • Vesicle membrane incorporated into presynaptic membrane • Neurotransmitter released • Vesicle membrane recovered by endocytosis

25. Two Broad Classes of Neural Receptor Types Ionotropic Receptors - transmitter-gated ion channels containing a protein channel pore.

26. Metabotropic Receptors - a subtype of membrane receptors at the surface or in vesicles of eukaryotic cells.

27. Principles of Chemical Synaptic Transmission • Excitatory and Inhibitory Postsynaptic Potentials: • EPSP:Transient postsynaptic membrane depolarization by presynaptic release of neurotransmitter • IPSP: Transient hyperpolarization of postsynaptic membrane potential caused by presynaptic release of neurotransmitter

30. Neurotransmitter Recovery and Degradation • Diffusion: Away from the synapse • Reuptake: Neurotransmitter re-enters presynaptic axon terminal • Enzymatic destruction inside terminal cytosol or synaptic cleft • Desensitization: e.g., AChE cleaves Ach to inactive state

31. Neuropharmacology • Effect of drugs on nervous system tissue • Receptor antagonists: Inhibitors of neurotransmitter receptors • Curare • Receptor agonists: Mimic actions of naturally occurring neurotransmitters • Nicotine • Defective neurotransmission: Root cause of neurological and psychiatric disorders

32. Principles of Synaptic Integration Synaptic Integration • Process by which multiple synaptic potentials combine within one postsynaptic neuron

33. Principles of Synaptic Integration EPSP Summation • Allows for neurons to perform sophisticated computations • Integration: EPSPs added together to produce significant postsynaptic depolarization • Spatial: EPSP generated simultaneously in different spaces • Temporal: EPSP generated at same synapse in rapid succession

34. The Contribution of Dendritic Properties to Synaptic Integration

35. IPSPs and Shunting Inhibition • Excitatory vs. inhibitory synapses: Bind different neurotransmitters, allow different ions to pass through channels • Membrane potential less negative than -65mV = hyperpolarizing IPSP • Shunting Inhibition: Inhibiting current flow from soma to axon hillock

36. Shunting Inhibition: Inhibiting current flow from soma to axon hillock

37. Edgar Douglas Adrian – physiologist who shared the 1932 Nobel Prize with Sherrington

38. END.