Chapter 3 Synapses

The Concept of the Synapse Neurons communicate by transmitting chemicals at junctions called “synapses” In 1906, Charles Scott Sherrington coined the term synapse to describe the specialized gap that existed between neurons.

The Concept of the Synapse Sherrington observed that repeated stimuli over a short period of time produced a stronger response. Led to the idea of temporal summation or that repeated stimuli can have a cumulative effect and can produce a nerve impulse when a single stimuli is too weak.

Figure 3.3: Recordings from a postsynaptic neuron during synaptic activation. Fig. 3-3, p. 54

The Concept of the Synapse Sherrington also noticed that several small stimuli on a similar location produced a reflex when a single stimuli did not. This led to the idea of spatial summation or that synaptic input from several locations can have a cumulative effect and trigger a nerve impulse.

Figure 3.4: Temporal and spatial summation. Fig. 3-4, p. 54

The Concept of the Synapse Excitatory postsynaptic potential (EPSP) is a graded potential that decays over time and space. Graded potentials are different than action potentials!! The cumulative effect of EPSPs are the basis for temporal and spatial summation.

The Concept of the Synapse Sherrington also noticed that during the reflex that occurred, the foot of a dog that was pinched retracted while the other three feet were extended. He suggested that an interneuron in the spinal cord sent an excitatory message to the flexor muscles of one leg and an inhibitory message was sent to the other three legs.

Fig. 3-5, p. 55 Figure 3.5: Antagonistic muscles. Flexor muscles draw an extremity toward the trunk of the body, whereas extensor muscles move an extremity away from the body. Fig. 3-5, p. 55

The Concept of the Synapse This led to the idea of inhibitory postsynaptic potential or the temporary hyperpolarization of a membrane. An IPSP occurs when synaptic input selectively opens the gates for positively charged potassium ions to leave the cell or for negatively charged chloride ions to enter the cells. Serves as an active “brake”, that suppresses excitation.

The Concept of the Synapse Neurons can have thousands of synapses. Both temporal and spatial summation can occur within a neuron. The likelihood of an action potential depends upon the ratio of IPSPs to EPSPs at a given moment.

Chemical Events at the Synapse Transmission of a message across the synapse occurs by chemical means. Neurotransmitters are chemicals that travel across the synapse and allow communication between neurons.

Chemical Events at the Synapse The major sequence of events that allow communication between neurons across the synapse are as follows: The neuron synthesizes chemicals that serve as neurotransmitters. Neurons store neurotransmitters in axon terminals or transport them there. An action potential triggers the release of neurotransmitters into the synaptic cleft.

Chemical Events at the Synapse (cont.) The neurotransmitters travel across the cleft and attach to receptors on the postsynaptic neuron. The neurotransmitters separate from the receptors. The neurotransmitters are taken back into the presynaptic neuron (reuptake), diffuse away, or are inactivated by chemicals. The postsynaptic cell may send negative feedback to slow the release of further neurotransmitters.

Figure 3.8: Some major events in transmission at a synapse. Fig. 3-8, p. 59

Chemical Events at the Synapse Major categories of neurotransmitters include the following: Amino acids — glutamate, GABA, Acetylcholine Monoamines – serotonin, dopamine, norephinephrine, epinephrine Purines --adenosine Gases –nitric oxide (not laughing gas!)

Chemical Events at the Synapse Neurons synthesize neurotransmitters and other chemicals from substances provided by the diet. Smaller neurotransmitters are synthesized in the presynaptic terminal and held there for release. Example: acetylcholine Larger neurotransmitters are synthesized in the cell body and transported down the axon. Example: peptides

Chemical Events at the Synapse Vesicles are tiny spherical packets located in the presynaptic terminal where neurotransmitters are held for release. Exocytosis refers to the excretion of the neurotransmitter from the presynaptic terminal into the synaptic cleft. Triggered by an action potential arriving fro the axon.

Fig. 3-10, p. 61 Figure 3.10: Anatomy of a synapse. (a) An electron micrograph showing a synapse from the cerebellum of a mouse. The small round structures are vesicles. (b) Electron micrograph showing axon terminals onto the soma of a neuron. (Source: From “Studying neural organization and aplysia with the scanning electron micrograph,” by E. R. Lewis, et al., Science, 1969, 165:1142. Copyright 1969 by the AAAS. Reprinted with permission of AAS and E. R. Lewis.) Fig. 3-10, p. 61

Chemical Events at the Synapse Transmission across the synaptic cleft by a neurotransmitter takes fewer than 10 microseconds. Most individual neurons release at least two or more different kinds of neurotransmitters. A neuron may respond to more types of neurotransmitters than it releases.

Chemical Events at the Synapse An ionotropic effect refers to when a neurotransmitter attaches to receptors and immediately opens ion channels. Ionotropic effects occur very quickly and are very short lasting. Most of the brain’s excitatory ionotropic synapses use glutamate or acetylcholine as a neurotransmitter.

Chemical Events at the Synapse Metabotropic effects refer to when a neurotransmitter attaches to a receptor and initiates a sequence of metabolic reactions that are slower and longer lasting. Metabotropic events include such behaviors as hunger, fear, thirst, or anger.

Chemical Events at the Synapse Metabotropic effects utilize a number of different neurotransmitters and are often called neuromodulators because they do not directly excite or inhibit the postsynaptic cell. Instead, neuromodulators: increase or decrease the release of other neurotransmitters alter the response of postsynaptic cells to various inputs.

Chemical Events at the Synapse A hormone is a chemical secreted by a gland or other cells that is transported to other organs by the blood where it alters activity. Endocrine glands are responsible for the production of hormones. Hormones are important for triggering long-lasting changes in multiple parts of the body.

Chemical Events at the Synapse Neurotransmitters released into the synapse do not remain and are subject to either inactivation or reuptake. Reuptake refers to when the presynaptic neuron takes up most of the neurotransmitter molecules intact and reuses it. Transporters are special membrane proteins that facilitate reuptake. Example: Serotonin is taken back up into the presynaptic terminal.

Chemical Events at the Synapse Examples of inactivation and reuptake include: Acetylcholine is broken down by acetylcholinesterase into acetate and choline. Some serotonin and catecholamine molecules are converted into inactive chemicals: COMT (catechol-o-methyltranferase)and MAO (monoamine oxidase) are enzymes that convert catecholamine transmitters into inactive chemicals.

Chemical Events at the Synapse Research has begun to investigate the role of events at the synapse and their effects on personality. Research suggests that some dopamine receptors may be related to “pleasure-seeking” and “thrill-seeking” behaviors.

Drugs and the Synapse The study of the influence of various kinds of drugs has provided us with knowledge about many aspects of neural communication at the synaptic level. Drugs either facilitate or inhibit activity at the synapse. Antagonistic drugs block the effects of neurotransmitters (e.g., novacaine, caffeine). Agonist drugs mimic or increase the effects of neurotransmitters (e.g., receptors in the brain respond to heroin, LSD and cocaine) Drugs alter various stages of synaptic processing.

Drugs and the Synapse Drugs work by doing one or more of the following to neurotransmitters: Increasing the synthesis. Causing vesicles to leak. Increasing release. Decreasing reuptake. Blocking the breakdown into inactive chemical. Directly stimulating or blocking postsynaptic receptors.

Drugs and the Synapse A drug has an affinity for a particular type of receptor if it binds to that receptor. Can vary from strong to weak. The efficacy of the drug is its tendency to activate the receptor . Drugs can have a high affinity but low efficacy.

Drugs and the Synapse Almost all abused drugs stimulate dopamine release in the nucleus accumbens small subcortical area rich in dopamine receptors an area responsible for feelings of pleasure Sustained bursts of dopamine in the nucleus accumbens inhibit cells that release the inhibitory neurotransmitter GABA

Figure 3.18: Location of the nucleus accumbens in the human brain. Nearly all abused drugs, as well as a variety of other highly reinforcing or addictive activities, increase dopamine release in the nucleus accumbens. Fig. 3-18, p. 72

Drugs and the Synapse Drugs are categorized according to their predominant action or effect upon behavior Stimulant drugs increase excitement, alertness, motor activity and elevate mood. Examples: amphetamines, cocaine, methylphenidate (Ritalin), MDMA (Ecstasy), nicotine Stimulant drugs directly stimulate dopamine receptor types D2, D3, and D4.

Fig. 3-19, p. 72 Figure 3.19: Effects of cocaine on the brain. As these positron-emission tomography (PET) scans show, cocaine lowers metabolism and overall activity in most of the brain. Red indicates highest activity, followed by yellow, green, and blue. A and B represent brain activity under normal conditions; H and I show activity after a cocaine injection. Fig. 3-19, p. 72

Drugs and the Synapse Amphetamine stimulate dopamine synapses by increasing the release of dopamine from the presynaptic terminal. Cocaine blocks the reuptake of dopamine, norepinephrine, and serotonin. Methylphenidate (Ritalin) also blocks the reuptake of dopamine but in a more gradual and more controlled rate.

Drugs and the Synapse Ecstasy increases the release of dopamine at low doses that account for its stimulant properties. Ecstasy increases the release of serotonin at higher doses accounting for its hallucinogenic properties. Research indicates ecstasy use may contribute to higher incidences of anxiety and depression as well as memory loss and other cognitive deficits.

Fig. 3-20, p. 73 Figure 3.20: Brain thinning in MDMA users. The figure on the left is the average brain scan for 21 adults who had never been substance abusers; the figure on the right is the average of 22 adults who had used MDMA frequently for years. Red represents the thickest area of brain cells, followed by yellow, green, blue, and purple. Note the apparent thinning in certain areas for the MDMA users. (Source: From “Structural abnormalities in the brains of human subjects who use methamphetamine,” by P. M. Thompson et al., Journal of Neuroscience, 24. Copyright 2004 by the Society for Neuroscience. Reprinted with permission. Fig. 3-20, p. 73

Drugs and the Synapse Nicotine stimulates one type of acetylcholine receptor known as the nicotinic receptor. Nicotinic receptors are found in the central nervous system, the nerve-muscle junction of skeletal muscles and in the nucleus accumbens (facilitate dopamine release).

Drugs and the Synapse Opiate drugs are those that are derived from (or similar to those derived from) the opium poppy. Opiates decrease sensitivity to pain and increase relaxation. Examples: morphine, heroin, methadone.

Drugs and the Synapse The brain produces peptides called endorphins. Endorphin synapses may contribute to certain kinds of reinforcement by inhibiting the release of GABA indirectly. Inhibiting GABA indirectly releases dopamine. Endorphins attach to the same receptors to which opiates attach.

Drugs and the Synapse Opiates also block the locus coeruleus. involved in our response to arousing stimuli by release of norepinephrine also involved in memory storage.

Drugs and the Synapse Tetrahydocannabinol (THC) is the active ingredient in marijuana. THC attaches to cannabinoid receptors throughout the brain but especially the cerebral cortex, cerebellum, basal ganglia, and hippocampus. Anandamide and 2-AG are the endogenous chemicals that attach to these receptors.

Drugs and the Synapse The location of the receptors in the brain may account for the subjective effects of loss of time, an intensification of sensory experience, and also memory impairment. The cannabinoid receptors are located on the presynaptic neuron and inhibit the release of glutamate and GABA.

Drugs and the Synapse Hallucinogenic drugs cause distorted perception. Many hallucinogenic drugs resemble serotonin in their molecular shape. Hallucinogenic drugs stimulate serotonin type 2A receptors (5-HT2A) at inappropriate times or for longer duration than usual thus causing their subjective effect.