Presentation is loading. Please wait.

Presentation is loading. Please wait.

Neurons, Synapses, and Communication

Similar presentations


Presentation on theme: "Neurons, Synapses, and Communication"— Presentation transcript:

1 Neurons, Synapses, and Communication
Neurons communicate with each other and other cells through specialized junctions called synapses, where plasma membranes of two cells come close together. Two types of synapses occur, electrical and chemical. Electrical synapses allow ionic currents to pass directly from one cell to the other through gap junctions so the action potential in the presynaptic neuron can directly trigger an action potential in the postsynaptic cell. Electrical synapses have a very short delay and are common in many invertebrates.

2 Two principal kinds of synapses: electrical and chemical

3 Electrical synaptic transmission.

4 Gap junctions are formed where hexameric pores called connexons connect with one between cells

5

6 Electrical synapses are built for speed

7 Electrical coupling is a way to synchronize neurons with one another

8 Electrical synapses are not presently considered to be the primary means of communication between neurons in the mammalian nervous system, but they may prove to be more important than presently recognized

9 Rectification and uni-directionality of electrical synapses
…not just simple bidirectional bridges between cells Conductance through gap junctions may be sensitive to the junctional potential (i.e the voltage drop between the two coupled cells), or sensitive to the membrane potential of either of the coupled cells Glial cells can also be connected by gap junctions, which allows synchronous oscillations of intracellular calcium

10 Electrical Synapses Gap junction-type communication important for rapidly synchronizing syncytia of cells as is observed in astrocytes, heart, and developing brains. Present in invertebrates to promote rapid defensive secretions. Problems with electrical: difficult to modulate gating of channels (exceptions exist cAMP, pH). Can't change sign, i.e. charge always flows "down hill.“ Electrical synaptic transmission requires that the presynaptic cell or terminal be larger than the postsynaptic cell for it to inject considerable charge, no real amplification mechanism.

11 Chemical Synaptic Transmission.
Definition: Communication between cells which involves the rapid release and diffusion of a substance to another cell where it binds to a receptor (at a localized site) resulting in a change in the postsynaptic cells properties.

12 Chemical transmission.
Contrary to electrical transmission multiple steps are required to release transmitter chemicals and for them to act on postsynaptic receptors, resulting in a time delay (can be as short as 0.1 msec). Directional, select localization of release machinery to presynaptic terminals and receptors to postsynaptic specializations. Can change sign by release of inhibitory transmitter. Highly modulatable as it has many steps presynaptic terminal and at the postsynaptic sites.

13 Steps to chemical synaptic transmission
First need to bring the presynaptic neuron to threshold at axon hillock Conduction down axon, length, R*C dependent Opening of voltage gated Ca channels Diffusion and action of Ca at release machinery Exocytosis and diffusion of transmitter in cleft Activation of postsynaptic receptors

14 Chemical synapses: the predominant means of communication between neurons

15 Types of Synapses CNS Synapses Axodendritic: Axon to dendrite
Axosomatic: Axon to cell body Axoaxonic: Axon to axon Dendrodendritic: Dendrite to dendrite Gray’s Type I: Asymmetrical, excitatory Gray’s Type II: Symmetrical, inhibitory

16

17 Synapse structure like real estate location, location, location!!
Multiple release sites NMJ

18 Criteria for a chemical transmitter
The transmitter substance must be synthesized in the presynaptic neuron. It must be present in the presynaptic terminal and released in amounts sufficient to result in the level of response produced by the endogenous transmitter. When applied exogenously the substance should mimic the effect of the endogenous transmitter. A specific mechanism must exist for removing the transmitter from the synaptic cleft.

19 Criteria that define a neurotransmitter:
Must be present at presynaptic terminal Must be released by depolarization, Ca++-dependent Specific receptors must be present

20 Neurotransmitters may be either small molecules or peptides
Mechanisms and sites of synthesis are different Peptides, or neuropeptides are synthesized in the endoplasmic reticulum and transported to the synapse, sometimes they are processed along the way. Neuropeptides are packaged in large dense-core vesicles Small molecule transmitters are synthesized at terminals, packaged into small clear-core vesicles (often referred to as ‘synaptic vesicles’

21 Neurotransmitter is released in discrete packages, or quanta

22 Failure analysis reveals that neurons release many quanta of neurotransmitter when stimulated, that all contribute to the response Quantal content: The number of quanta released by stimulation of the neuron Quantal size: How size of the individual quanta

23 Quanta correspond to release of individual synaptic vesicles
EM images and biochemistry suggest that a MEPP could be caused by a single vesicle EM studies revealed correlation between fusion of vesicles with plasma membrane and size of postsynaptic response

24 Quantal aspects of release at the neuromuscular junction
At the neuromuscular junction small spontaneous potentials (depolarizations) termed miniature end plate potentials are observed. The amplitude of evoked responses (due to calcium influx) is always an integer multiple of the unitary response. Shown that calcium increases the probability of observing a unitary response. These data suggested the existence of transmitter quanta or packets. Evoked transmission mediated by the release of ~ 150 quanta over a 1-3 ms period. Each quantum leads to about 0.5 mV depolarization.

25 Calcium influx is necessary for neurotransmitter release
Voltage-gated calcium channels

26 Calcium influx is sufficient for neurotransmitter release

27 Synaptic release II The synaptic vesicle release cycle Tools and Pools Molecular biology and biochemistry of vesicle release: Docking Priming Fusion Recovery and recycling of synaptic vesicles

28 The synaptic vesicle cycle

29 How do we study vesicle dynamics? Morphological techniques
Electron microscopy to obtain static pictures of vesicle distribution; TIRFM (total internal reflection fluorescence microscopy) to visualize movement of vesicles close to the membrane Physiological studies Chromaffin cells Neuroendocrine cells derived from adrenal medulla with large dense-core vesicles. Can measure membrane fusion, or direct release of catecholamine transmitters using carbon fiber electrodes Neurons Measure release of neurotransmitter from a presynaptic cell by quantifying the response of a postsynaptic cell Genetics Delete or overexpress proteins in mice, worms, or flies, and analyze phenotype using the above techniques

30 Synaptic vesicle release consists of three principal steps: Docking
Docked vesicles lie close to plasma membrane (within 30 nm) Priming Primed vesicles can be induced to fuse with the plasma membrane by sustained depolarization, high K+, elevated Ca++, hypertonic sucrose treatment Fusion Vesicles fuse with the plasma membrane to release transmitter. Physiologically this occurs near calcium channels, but can be induced experimentally over larger area. The ‘active zone’ is the site of physiological release, and can sometimes be recognized as an electron-dense structure. .

31 In CNS neurons, vesicles are divided into
Reserve pool (80-95%) Recycling pool (5-20%) Readily-releasable pool (0.1-2%; 5-10 synapses per active zone) A small fraction of vesicles (the recycling pool) replenishes the RRP upon mild stimulation. Strong stimulation causes the reserve pool to mobilize and be released

32 Vesicle release requires many proteins on vesicle and plasma membrane

33

34 Priming Vesicles in the reserve pool undergo priming to enter the readily-releasable pool At a molecular level, priming corresponds to the assembly of the SNARE complex

35 Synaptotagmin functions as a calcium sensor, promoting vesicle fusion

36 Synaptic vesicles recycle post-fusion

37 Principles of Chemical Synaptic Transmission
Neurotransmitter Receptors and Effectors Ionotropic: Transmitter-gated ion channels Metabotropic: G-protein-coupled receptor

38 Principles of Chemical Synaptic Transmission
G-Protein-Coupled Receptors Steps of neurotransmitter action Bind to receptor proteins Activate small proteins Activate “effector” proteins Second messengers Metabotropic receptors: Metabolic effects Same neurotransmitter: Different postsynaptic actions ACh Effect: Heart, skeletal muscle

39

40 Principles of Chemical Synaptic Transmission
Autoreceptors Presynaptic receptors sensitive to neurotransmitter released by presynaptic terminal Act as safety valve to reduce release when levels are high in synaptic cleft (autoregulation)

41 Principles of Chemical Synaptic Transmission
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

42 Post synaptic potentials
IPSP: Transient hyperpolarization of postsynaptic membrane potential caused by presynaptic release of neurotransmitter EPSP:Transient postsynaptic membrane depolarization by presynaptic release of neurotransmitter

43 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

44

45 Principles of Synaptic Integration
Excitable Dendrites Dendrites of neurons of voltage-gated sodium, calcium, and potassium channels Can act as amplifiers (vs. passive) Dendritic sodium channels: May carry electrical signals in opposite direction, from soma outward along dendrites

46 Principles of Synaptic Integration
Inhibition Action of synapses to take membrane potential away from action potential threshold Exert powerful control over neuron output

47 Principles of Synaptic Integration
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

48 Principles of Synaptic Integration
The Geometry of Excitatory and Inhibitory Synapses Excitatory synapses Gray’s type I morphology Clustered on soma and near axon hillock Inhibitory synapses Gray’s type II morphology

49 Type I Excitatory Type II Inhibitory

50 Principles of Synaptic Integration
Modulation Synaptic transmission that modifies effectiveness of EPSPs generated by other synapses with transmitter-gated ion channels Example: Activating NE β receptor Suggest inserting figure 5.21 of NE example


Download ppt "Neurons, Synapses, and Communication"

Similar presentations


Ads by Google