PSYC2410 â Chapter 4 4.1 Resting Membrane ... amazonaws com
PSYC2410 – Chapter 4 *to note: images important in textbook are marked by green and yellow stickers!
4.1 Resting Membrane Potential Membrane potential: difference in electrical charge between the inside and the outside of a cell. Recording a membrane potential: to record a neuron’s membrane potential, position the tip of one electrode inside the neuron and the top of another electrode outside the neurone in the extracellular fluid. The intracellular electrodes are called microelectrodes: their tips are less than one-thousandth of a millimeter in diameter. Resting membrane potential: about -70mV in neurons, the neuron is said to be polarized. Ionic Basis of the Resting Potential:
The resting potential results from the fact that the ratio of negative to positive charges is greater inside the neuron than outside. Based on 4 factors: o Random motion: ions are in constant random motion and tend to become evenly distributed as they move down the concentration gradient o Electrostatic pressure: any accumulation of charges, positive or negative, in one area tends to be dispersed by the repulsion among the like charges in the vicinity and the attraction of opposite charges concentrated elsewhere. o Passive ion distribution: the passive property of the neural membrane hat contributes to the unequal disposition + + of Na , K and Cl and protein ions is its differential permeability to those ions. + + In resting neurons, K and Cl ions pass readily through the neural membrane, Na ions pass through it with difficulty and the negatively charged protein ions do not pass trhough it at all. At rest the unequal distribution of Cl ions across the neural membrane is maintained in equilibrium by the balance between the tendency for Cl ions to move down their gradient into the neuron and the 7- mV of electrostatic + pressure driving them out. 90 mV is electrostatic pressure is required to keep K ions from moving out of + the neuron. And for Na 50 mV of pressure is required to keep them from moving into the neuron, added + to the 70 mV of pressure acting to move them in the same direction; thus 120 mV is acting to force Na ions into resting neurons. o Active ion distribution: + + Sodium-potassium pumps: move 3 Na out, and bring 2 K in.
4.2 Generation and Conduction of Postsynaptic Potentials When neurotransmitters bind to post-synaptic membrane, have one of 2 effects:
Depolarize: decrease the resting membrane potential o Excitatory postsynaptic potentials (EPSPs): they increase the likelihood that a neuron will fire Hyperpolarize: increase the resting membrane potential o Inhibitory postsynaptic potentials (IPSPs): decrease the likelihood of a neuron firing
Both EPSPs and IPSPs are graded responses: the amplitudes of EPSPs and IPSPs are proportional to the intensity of the signals that elicit them. Weak signals elicit small postsynaptic potentials and strong signals elicit large ones. Their transmission is extremely rapid, and can be assumed to be instantaneous for most purposes. Their transmission is Decremental: they decrease in amplitude as they travel through the neuron
4.3 Integration of Postsynaptic Potentials and Generation of Action Potentials
Whether or not a neurone fires depends on the balance between the excitatory and inhibitory signals reaching its axon. EPSPs and IPSPs created by the action of neurotransmitters at particular receptive sites on a neuron’s membrane are conducted instantly and decrementally to the axon hillock.
PSYC2410 – Chapter 4
If the sum of depolarizations and hyperpolarizations reaching the section of the axon adjacent to the hillock at any time is sufficient to depolarize the membrane to its threshold of excitataion (~ -65 mV) an action potential is generated. o Integration: combining a number of individual signals into one overall signal. Neuron’s integrate signals in 2 ways: over space and over time. o Spatial summation (p.81) o Temporal summation (p.82) The action potential is a massive but momentary (1 millisecond) reversal of the membrane potential from about -70 mV to +50 mV. Action potentials are not graded responses, all or none,
4.4 Conduction of Actions Potentials Ionic Basis of Action Potentials: action potentials are produce and conducted through the action of voltage-activated ion channels. When the potential is reduced to the threshold potential, the voltage-activated sodium channels in the axon membrane open and + + Na ions rush in, driving the potential from -70 mV to +50 mV. This rapid influx activates potassium channels. K ions near the membrane are driven out of the cell through these channels, first by their relatively high internal concentration and then when the action potential is near its peark, by the positive internal charge. After about 1 millisecond, the sodium channels close. This marks + the end of the rising phase of the action potential and the beginning of repolarization by the continued efflux of K ions. Once + repolarization is achieved, the potassium channels gradually close. This gradual close causes too many K ions to flow out, so the neuron becomes hyperpolarized for a brief time. Action potential only involves those ions close to the membrane, and thus has little effect on the relative concentrations of various ions inside and outside the neurone. Refractory Period: responsible for the fact that action potentials normally travel along axons in only on direction. The refractory period is responsible for the fact that the rate of neural firing is related to the intensity of the stimulation. Absolute refractory period: 1 to 2 milliseconds after the initiation of an action potential during which it is impossible to elicit a second one. Relative refractory period: it is possible to fire the neuron again but need higher-than-normal levels of stimulation Axonal Conduction of Action Potentials: conduction of action potentials along axons is nondecremental and are conducted more slowly than EPSPs or IPSPs because those are passive, and action potentials are active (require E). Antidromic conduction: when action potential is stimulated at the terminal buttons and transmitted back to the cell body Orthodromic conduction: conduction from cell body to axon terminal buttons (natural) Conduction in Myelinated Axons: in myelinated axons, ions can only pass through the membrane at Nodes of Ranvier, and axonal sodium channels are concentrated at the nodes. Action potentials are conducted passively and decrementally in the parts covered in myelin to the nodes of Ranvier, where the voltage-activated sodium channels open and generate another full-blown action potential, which is then conducted passively along to the next node. Myelination increases the speed of axonal conduction because conduction along the myelinated segments is passive and is instantaneous, although there is a slight delay at each node, but it is still much faster than in unmyelinated axons. Saltatory conduction: transmission of action potentials in myelinated axons. The Velocity of Axonal Conduction: conduction is faster in large-diameter axons, and in myelinated axons. Mammalian motor neurons are large and myelinated and can reach speeds up to 100 m/s. Small unmyelinated axons conduct action potentials at about 1 m/s. In humans, the max. velocity of conduction in motor neurons is about 60m/s. Conduction in Neurons without Axons: conduction in interneurons is usually passive and decremental. Hodgkin-Huxley model is based on giant squid motor neurons, and therefore must be applied to cerebral neurons with caution. It is clear that cerebral neurons are far more complex than motor neurons. The following are some properties of cerebral neurons that are not shared by motor neurons:
Many cerebral neurons fire continually even when they receive no input Axons of some cerebral neurons can actively conduct both graded signals and action potentials
PSYC2410 – Chapter 4
Action potentials of all motor neurons are the same, but action potentials of different classes of cerebral neurons vary greatly in duration, amplitude and frequency. Many cerebral neurons have no axons and do not display action potentials The dendrites of some cerebral neurons can actively conduct action potentials
4.5 Synaptic Transmission: Chemical Transmission of Signals among Neurons Structure of Synapses
Axodendritic synapses: synapses of axon terminal buttons on dendrites. Many axodendritic synapses terminate on dendritic spines (nodules of various shapes that are located on the surfaces of many dendrites). Axosomatic synapses: synapses of axon terminal buttons on somas (cell bodies) Dendrodendritic synapses: often capable of transmission in either direction Axoaxonic synapses: very important because they can mediate presynaptic facilitation and inhibition. An axoaxonic synapse on, or near, a terminal button can selectively facilitate or inhibit the effects of that button on the postsynaptic neuron. The advantage of presynaptic facilitation and inhibition (compared to EPSPs and IPSPs) is that they can selectively influence one particular synapse rather than the entire presynaptic neuron. Directed synapses: synapses at which the site of neurotransmitter release and the site of neurotransmitter reception are in close proximity. Nondirected synapses: synapses at which the site of release is at some distance from the site of reception. Neurotransmitter molecules are released from a series of varicosities (bulges or swellings) along the axon and its branches and thus are widely dispersed to surrounding targets. Often referred to as string-of-beads synapses.
The Synthesis, Packaging, and Transport of Neurotransmitter Molecules
Coexistence: neurons synthesize and contain two neurotransmitters. So far, most cases of coexistence have involved one small neurotransmitter and one large neuropeptide. Small neurotransmitters: typically synthesized in the cytoplasm of the terminal button and packaged in synaptic vesicles by the Golgi complex. The vesicles are stored in clusters next to the presynaptic membrane Large neurotransmitters: assembled in the cytoplasm of the cell body on ribosomes then packaged in vesicles by the Golgi complex and transported by microtubules to the terminal buttons at ~ 40cm/day. Vesicles are usually larger since neuropeptides are larger and do not congregate as closely to the presynaptic membrane as the other vesicles do. o Neuropeptides: short amino acid chains comprising between 3 and 36 aas; “short proteins”.
The Release of Neurotransmitter Molecules
Exocytosis: the process of neurotransmitter release. o At rest, synaptic vesicles that contain small-molecule neurotransmitters tend to congregate near sections of the presynaptic membrane that are particularly rich in voltage-activated calcium channels. 2+ o When stimulated by action potentials, these channels open, and Ca ions enter the button whih causes synaptic vesicles to fuse with the presynaptic membrane and empty their contents into the synaptic cleft. o At many, but not all, synapses, one action potential causes the release of one vesicle. o Small-molecule neurotransmitters are typically released in a pulse each time an action potential triggers a 2+ momentary influx of Ca ions through the presynaptic membrane 2+ o Neuropeptides are typically released gradually in response to general increases in the level of intracellular Ca ions, in a general increase in the rate of neuron firing.
The Activation of Receptors by Neurotransmitter Molecules: once released, neurotransmitters produce signals in postsynaptic neurons by binding to receptors in the postsynaptic membrane. Each receptor is a protein that contains binding sites for only particular neurotransmitters. Any molecule that binds to another is referred to as its ligand. Most neurotransmitters bind to several different types of receptors; each neurotransmitter has receptor subtypes that it can bind to. Various receptor subtypes are typically located in different brain areas and typically respond to the neurotransmitter in different ways. *yellow sticker for image on p.89*
PSYC2410 – Chapter 4
Ionotropic receptors: receptors associated with ligand-activated ion channels. Binding of ligand usually opens or closes an ion channel, inducing an immediate postsynaptic potential. Metabotropic receptors: receptors associated with signal proteins and G proteins (guanosine-triphosphate-sensitive proteins). More prevalent that ionotropic receptors and their effects are slower to develop, longer-lasting, more diffuse and more varied. Each is attached to a serpentine signal protein that winds its way back and forth through the cell membrane seven times. The metabotropic receptor is attached to a portion of the signal protein outside the neuron; the G protein is attached to a portion of the signal protein inside the neuron. When a neurotransmitter binds to a metabotropic receptor, a subunit of the G protein breaks away. The subunit may bind to an ion channel in the membrane inducing an EPSP or IPSP or it may trigger the synthesis of a second messenger which diffuses through the cytoplasm and may influence the activities of the neuron in a variety of ways: may enter the nucleus and bind to DNA influencing/changing genetic expression. o Autoreceptor: bind their neuron’s own neurotransmitter molecule on the presynaptic membrane. Monitor number of neurotransmitter molecules in the synapse, to reduce subsequent release when the levels are high and to increase subsequent release when they’re low.
Small molecule neurotransmitters tend to be released into directed synapses and to activate either ionotropic receptors or metabotropic receptors that act directly on ion channels. Neuropeptides tend to be released diffusely and virtually all bind to metabotropic receptors that act through second messengers. Small-molecule neurotransmitters produce rapid, brief excitatory or inhibitory signals; neuropeptides transmit slow, diffuse, long-lasting signals. The reuptake, Enzymatic Degradation and Recycling of Neurotransmitter Molecules
Reuptake: most common, neurotransmitters are taken back into the presynaptic neuron by transporter mechanisms. Enzymatic Degradation: neurotransmitters are broken apart in the synapse by enzymes, and recycled.
Glial Function and Synaptic Transmission
Gap Junctions: narrow spaces between adjacent neurons that are bridged by fine tubular channels, called connexins, that contain cytoplasm. Allows electrical signals and small molecules to pass between neurons. Communication across them is very fast because it does not involve active mechanisms and they permit communication in either direction. Glial cells communicate through gap junctions.
4.6 Neurotransmitters
Amino acids: majority of fast-acting, directed synapses in the CNS are aas. o Glutamate: most prevalent excitatory neurotransmitter in the CNS o Aspartate o Glycine o Gamma-Aminobutyric acid (GABA): synthesizes from glutamate, mainly inhibitory effects with some excitatory effects at certain synapses Monoamines: each is synthesized from a single aa. They are slightly larger than aa neurotransmitters and their effects tend to be more diffuse. The monoamines are present in small groups of neurons whose cell bodies are for the most part located in the brain stem. These neurons have highly branched axons with many varicosities (string-of-beads synapses), from which monoamine neurotransmitters are released into the extracellular fluid. o Catecholamines: synthesized from the aa tyrosineL-dopa dopamine Dopamine Epinephrine: have all the enzymes present in neurons that release norepinephrine, along with an extra enzyme that converts norepinephrine to epinephrine. Neurons that release epinephrine are called adrenergic. Norepinephrine: neurons that release norepinephrine have an extra enzyme which converts the dopamine in them to norepinephrine. Neurons that release norepinephrine are called noradrenergic. o Indolamines: Serotonin (5-hydroxytryptamine or 5-HT): synthesized from tryptophan.
PSYC2410 – Chapter 4
Acetylcholine: a small-molecule neurotransmitter created by adding an acetyl group to a choline molecule. It is the neurotransmitter at neuromuscular junctions, at many of the synapses in the autonomic nervous system, and at synapses in several parts of the CNS. It is broken down in the synapse by acetylcholinesterase. Neurons that release acetylcholine are called cholinergic. o Nicotinic receptors: ionotropic. In the PNS, many nicotinic receptors occur at the junctions between motor neurons and muscle fibers o Muscarinic receptors: metabotropic. In the PNS, many muscarinic receptors are located in the autonomic nervous system (ANS). Atropine: (main active ingredient in belladonna plant) a receptor blocker that exerts it antagonist effect by binding to muscarinic receptors blocking the effects of acetylcholine on them. Its pupil dilating effects due to blocking receptors in the ANS. Its memory effects are due to its binding to muscarinic receptors in the CNS. Botox: neurotoxin released by a bacterium often found in spoiled food, is a nicotinic antagonist. It blocks the release of acetylcholine at neuromuscular junctions and is thus a deadly poison. Unconventional neurotransmitters: o Endocannabinoids: neurotransmitters that are similar to delta-9-tetrahydrocannabinol (THC) that main psychoactive constituent of marijuana. They are synthesized from fatty compounds in the cell membrane and tend to be released from the dendrites and cell body, and tend to have most effects on presynaptic neurons, inhibiting subsequent synaptic transmission. Anandamide (means “eternal bliss”) o Soluble-gas neurotransmitters: produced in the neural cytoplasm and immediately diffuse through the cell membrane into the extracellular fluid and then into nearby cells. They easily pass through cell membranes because they are soluble in lipids. They stimulate the production of second messengers and are then deactivated by being converted to other molecules. Have been shown to be involved in retrograde transmission. At some synapses they transmit feedback signals from the post-synaptic neuron back to the presynaptic neuron, to regulate activity of presynaptic neurons. Nitric oxide Carbon monoxide (Large molecule) Neuropeptides: over 100 have been identified. They often function not only just as neurotransmitters o Pituitary peptides: neuropeptides that were first identified as hormones released by the pituitary o Hypothalamic peptides: neuropeptides that were first identified as hormones released by the hypothalamus o Brain-gut peptides: neuropeptides that were first discovered in the gut o Opioid peptides: neuropeptides that are similar in structure to the active ingredients of opium. All have metabotropic receptors. Enkephalins Endorphins o Miscellaneous peptides: catch-all category that contains all of the neuropeptide transmitters
4.7 Pharmacology of Synaptic Transmission and Behaviour Agonists: facility the effects of a particular neurotransmitter Antagonists: inhibit the effects of a particular neurotransmitter Receptor blockers: bind to postsynaptic receptors without activating them and block the access of the neurotransmitter Behavioural Pharmacology: Three Influential Lines of Research
4.1 Resting Membrane Potential Membrane potential: difference in electrical charge between the inside and the outside of a cell. Recording a membrane potential: to record a neuron’s membrane potential, position the tip of one electrode inside the neuron and the top of another electrode outside the neurone in the extracellular fluid. The intracellular electrodes are called microelectrodes: their tips are less than one-thousandth of a millimeter in diameter. Resting membrane potential: about -70mV in neurons, the neuron is said to be polarized. Ionic Basis of the Resting Potential:
The resting potential results from the fact that the ratio of negative to positive charges is greater inside the neuron than outside. Based on 4 factors: o Random motion: ions are in constant random motion and tend to become evenly distributed as they move down the concentration gradient o Electrostatic pressure: any accumulation of charges, positive or negative, in one area tends to be dispersed by the repulsion among the like charges in the vicinity and the attraction of opposite charges concentrated elsewhere. o Passive ion distribution: the passive property of the neural membrane hat contributes to the unequal disposition + + of Na , K and Cl and protein ions is its differential permeability to those ions. + + In resting neurons, K and Cl ions pass readily through the neural membrane, Na ions pass through it with difficulty and the negatively charged protein ions do not pass trhough it at all. At rest the unequal distribution of Cl ions across the neural membrane is maintained in equilibrium by the balance between the tendency for Cl ions to move down their gradient into the neuron and the 7- mV of electrostatic + pressure driving them out. 90 mV is electrostatic pressure is required to keep K ions from moving out of + the neuron. And for Na 50 mV of pressure is required to keep them from moving into the neuron, added + to the 70 mV of pressure acting to move them in the same direction; thus 120 mV is acting to force Na ions into resting neurons. o Active ion distribution: + + Sodium-potassium pumps: move 3 Na out, and bring 2 K in.
4.2 Generation and Conduction of Postsynaptic Potentials When neurotransmitters bind to post-synaptic membrane, have one of 2 effects:
Depolarize: decrease the resting membrane potential o Excitatory postsynaptic potentials (EPSPs): they increase the likelihood that a neuron will fire Hyperpolarize: increase the resting membrane potential o Inhibitory postsynaptic potentials (IPSPs): decrease the likelihood of a neuron firing
Both EPSPs and IPSPs are graded responses: the amplitudes of EPSPs and IPSPs are proportional to the intensity of the signals that elicit them. Weak signals elicit small postsynaptic potentials and strong signals elicit large ones. Their transmission is extremely rapid, and can be assumed to be instantaneous for most purposes. Their transmission is Decremental: they decrease in amplitude as they travel through the neuron
4.3 Integration of Postsynaptic Potentials and Generation of Action Potentials
Whether or not a neurone fires depends on the balance between the excitatory and inhibitory signals reaching its axon. EPSPs and IPSPs created by the action of neurotransmitters at particular receptive sites on a neuron’s membrane are conducted instantly and decrementally to the axon hillock.
PSYC2410 – Chapter 4
If the sum of depolarizations and hyperpolarizations reaching the section of the axon adjacent to the hillock at any time is sufficient to depolarize the membrane to its threshold of excitataion (~ -65 mV) an action potential is generated. o Integration: combining a number of individual signals into one overall signal. Neuron’s integrate signals in 2 ways: over space and over time. o Spatial summation (p.81) o Temporal summation (p.82) The action potential is a massive but momentary (1 millisecond) reversal of the membrane potential from about -70 mV to +50 mV. Action potentials are not graded responses, all or none,
4.4 Conduction of Actions Potentials Ionic Basis of Action Potentials: action potentials are produce and conducted through the action of voltage-activated ion channels. When the potential is reduced to the threshold potential, the voltage-activated sodium channels in the axon membrane open and + + Na ions rush in, driving the potential from -70 mV to +50 mV. This rapid influx activates potassium channels. K ions near the membrane are driven out of the cell through these channels, first by their relatively high internal concentration and then when the action potential is near its peark, by the positive internal charge. After about 1 millisecond, the sodium channels close. This marks + the end of the rising phase of the action potential and the beginning of repolarization by the continued efflux of K ions. Once + repolarization is achieved, the potassium channels gradually close. This gradual close causes too many K ions to flow out, so the neuron becomes hyperpolarized for a brief time. Action potential only involves those ions close to the membrane, and thus has little effect on the relative concentrations of various ions inside and outside the neurone. Refractory Period: responsible for the fact that action potentials normally travel along axons in only on direction. The refractory period is responsible for the fact that the rate of neural firing is related to the intensity of the stimulation. Absolute refractory period: 1 to 2 milliseconds after the initiation of an action potential during which it is impossible to elicit a second one. Relative refractory period: it is possible to fire the neuron again but need higher-than-normal levels of stimulation Axonal Conduction of Action Potentials: conduction of action potentials along axons is nondecremental and are conducted more slowly than EPSPs or IPSPs because those are passive, and action potentials are active (require E). Antidromic conduction: when action potential is stimulated at the terminal buttons and transmitted back to the cell body Orthodromic conduction: conduction from cell body to axon terminal buttons (natural) Conduction in Myelinated Axons: in myelinated axons, ions can only pass through the membrane at Nodes of Ranvier, and axonal sodium channels are concentrated at the nodes. Action potentials are conducted passively and decrementally in the parts covered in myelin to the nodes of Ranvier, where the voltage-activated sodium channels open and generate another full-blown action potential, which is then conducted passively along to the next node. Myelination increases the speed of axonal conduction because conduction along the myelinated segments is passive and is instantaneous, although there is a slight delay at each node, but it is still much faster than in unmyelinated axons. Saltatory conduction: transmission of action potentials in myelinated axons. The Velocity of Axonal Conduction: conduction is faster in large-diameter axons, and in myelinated axons. Mammalian motor neurons are large and myelinated and can reach speeds up to 100 m/s. Small unmyelinated axons conduct action potentials at about 1 m/s. In humans, the max. velocity of conduction in motor neurons is about 60m/s. Conduction in Neurons without Axons: conduction in interneurons is usually passive and decremental. Hodgkin-Huxley model is based on giant squid motor neurons, and therefore must be applied to cerebral neurons with caution. It is clear that cerebral neurons are far more complex than motor neurons. The following are some properties of cerebral neurons that are not shared by motor neurons:
Many cerebral neurons fire continually even when they receive no input Axons of some cerebral neurons can actively conduct both graded signals and action potentials
PSYC2410 – Chapter 4
Action potentials of all motor neurons are the same, but action potentials of different classes of cerebral neurons vary greatly in duration, amplitude and frequency. Many cerebral neurons have no axons and do not display action potentials The dendrites of some cerebral neurons can actively conduct action potentials
4.5 Synaptic Transmission: Chemical Transmission of Signals among Neurons Structure of Synapses
Axodendritic synapses: synapses of axon terminal buttons on dendrites. Many axodendritic synapses terminate on dendritic spines (nodules of various shapes that are located on the surfaces of many dendrites). Axosomatic synapses: synapses of axon terminal buttons on somas (cell bodies) Dendrodendritic synapses: often capable of transmission in either direction Axoaxonic synapses: very important because they can mediate presynaptic facilitation and inhibition. An axoaxonic synapse on, or near, a terminal button can selectively facilitate or inhibit the effects of that button on the postsynaptic neuron. The advantage of presynaptic facilitation and inhibition (compared to EPSPs and IPSPs) is that they can selectively influence one particular synapse rather than the entire presynaptic neuron. Directed synapses: synapses at which the site of neurotransmitter release and the site of neurotransmitter reception are in close proximity. Nondirected synapses: synapses at which the site of release is at some distance from the site of reception. Neurotransmitter molecules are released from a series of varicosities (bulges or swellings) along the axon and its branches and thus are widely dispersed to surrounding targets. Often referred to as string-of-beads synapses.
The Synthesis, Packaging, and Transport of Neurotransmitter Molecules
Coexistence: neurons synthesize and contain two neurotransmitters. So far, most cases of coexistence have involved one small neurotransmitter and one large neuropeptide. Small neurotransmitters: typically synthesized in the cytoplasm of the terminal button and packaged in synaptic vesicles by the Golgi complex. The vesicles are stored in clusters next to the presynaptic membrane Large neurotransmitters: assembled in the cytoplasm of the cell body on ribosomes then packaged in vesicles by the Golgi complex and transported by microtubules to the terminal buttons at ~ 40cm/day. Vesicles are usually larger since neuropeptides are larger and do not congregate as closely to the presynaptic membrane as the other vesicles do. o Neuropeptides: short amino acid chains comprising between 3 and 36 aas; “short proteins”.
The Release of Neurotransmitter Molecules
Exocytosis: the process of neurotransmitter release. o At rest, synaptic vesicles that contain small-molecule neurotransmitters tend to congregate near sections of the presynaptic membrane that are particularly rich in voltage-activated calcium channels. 2+ o When stimulated by action potentials, these channels open, and Ca ions enter the button whih causes synaptic vesicles to fuse with the presynaptic membrane and empty their contents into the synaptic cleft. o At many, but not all, synapses, one action potential causes the release of one vesicle. o Small-molecule neurotransmitters are typically released in a pulse each time an action potential triggers a 2+ momentary influx of Ca ions through the presynaptic membrane 2+ o Neuropeptides are typically released gradually in response to general increases in the level of intracellular Ca ions, in a general increase in the rate of neuron firing.
The Activation of Receptors by Neurotransmitter Molecules: once released, neurotransmitters produce signals in postsynaptic neurons by binding to receptors in the postsynaptic membrane. Each receptor is a protein that contains binding sites for only particular neurotransmitters. Any molecule that binds to another is referred to as its ligand. Most neurotransmitters bind to several different types of receptors; each neurotransmitter has receptor subtypes that it can bind to. Various receptor subtypes are typically located in different brain areas and typically respond to the neurotransmitter in different ways. *yellow sticker for image on p.89*
PSYC2410 – Chapter 4
Ionotropic receptors: receptors associated with ligand-activated ion channels. Binding of ligand usually opens or closes an ion channel, inducing an immediate postsynaptic potential. Metabotropic receptors: receptors associated with signal proteins and G proteins (guanosine-triphosphate-sensitive proteins). More prevalent that ionotropic receptors and their effects are slower to develop, longer-lasting, more diffuse and more varied. Each is attached to a serpentine signal protein that winds its way back and forth through the cell membrane seven times. The metabotropic receptor is attached to a portion of the signal protein outside the neuron; the G protein is attached to a portion of the signal protein inside the neuron. When a neurotransmitter binds to a metabotropic receptor, a subunit of the G protein breaks away. The subunit may bind to an ion channel in the membrane inducing an EPSP or IPSP or it may trigger the synthesis of a second messenger which diffuses through the cytoplasm and may influence the activities of the neuron in a variety of ways: may enter the nucleus and bind to DNA influencing/changing genetic expression. o Autoreceptor: bind their neuron’s own neurotransmitter molecule on the presynaptic membrane. Monitor number of neurotransmitter molecules in the synapse, to reduce subsequent release when the levels are high and to increase subsequent release when they’re low.
Small molecule neurotransmitters tend to be released into directed synapses and to activate either ionotropic receptors or metabotropic receptors that act directly on ion channels. Neuropeptides tend to be released diffusely and virtually all bind to metabotropic receptors that act through second messengers. Small-molecule neurotransmitters produce rapid, brief excitatory or inhibitory signals; neuropeptides transmit slow, diffuse, long-lasting signals. The reuptake, Enzymatic Degradation and Recycling of Neurotransmitter Molecules
Reuptake: most common, neurotransmitters are taken back into the presynaptic neuron by transporter mechanisms. Enzymatic Degradation: neurotransmitters are broken apart in the synapse by enzymes, and recycled.
Glial Function and Synaptic Transmission
Gap Junctions: narrow spaces between adjacent neurons that are bridged by fine tubular channels, called connexins, that contain cytoplasm. Allows electrical signals and small molecules to pass between neurons. Communication across them is very fast because it does not involve active mechanisms and they permit communication in either direction. Glial cells communicate through gap junctions.
4.6 Neurotransmitters
Amino acids: majority of fast-acting, directed synapses in the CNS are aas. o Glutamate: most prevalent excitatory neurotransmitter in the CNS o Aspartate o Glycine o Gamma-Aminobutyric acid (GABA): synthesizes from glutamate, mainly inhibitory effects with some excitatory effects at certain synapses Monoamines: each is synthesized from a single aa. They are slightly larger than aa neurotransmitters and their effects tend to be more diffuse. The monoamines are present in small groups of neurons whose cell bodies are for the most part located in the brain stem. These neurons have highly branched axons with many varicosities (string-of-beads synapses), from which monoamine neurotransmitters are released into the extracellular fluid. o Catecholamines: synthesized from the aa tyrosineL-dopa dopamine Dopamine Epinephrine: have all the enzymes present in neurons that release norepinephrine, along with an extra enzyme that converts norepinephrine to epinephrine. Neurons that release epinephrine are called adrenergic. Norepinephrine: neurons that release norepinephrine have an extra enzyme which converts the dopamine in them to norepinephrine. Neurons that release norepinephrine are called noradrenergic. o Indolamines: Serotonin (5-hydroxytryptamine or 5-HT): synthesized from tryptophan.
PSYC2410 – Chapter 4
Acetylcholine: a small-molecule neurotransmitter created by adding an acetyl group to a choline molecule. It is the neurotransmitter at neuromuscular junctions, at many of the synapses in the autonomic nervous system, and at synapses in several parts of the CNS. It is broken down in the synapse by acetylcholinesterase. Neurons that release acetylcholine are called cholinergic. o Nicotinic receptors: ionotropic. In the PNS, many nicotinic receptors occur at the junctions between motor neurons and muscle fibers o Muscarinic receptors: metabotropic. In the PNS, many muscarinic receptors are located in the autonomic nervous system (ANS). Atropine: (main active ingredient in belladonna plant) a receptor blocker that exerts it antagonist effect by binding to muscarinic receptors blocking the effects of acetylcholine on them. Its pupil dilating effects due to blocking receptors in the ANS. Its memory effects are due to its binding to muscarinic receptors in the CNS. Botox: neurotoxin released by a bacterium often found in spoiled food, is a nicotinic antagonist. It blocks the release of acetylcholine at neuromuscular junctions and is thus a deadly poison. Unconventional neurotransmitters: o Endocannabinoids: neurotransmitters that are similar to delta-9-tetrahydrocannabinol (THC) that main psychoactive constituent of marijuana. They are synthesized from fatty compounds in the cell membrane and tend to be released from the dendrites and cell body, and tend to have most effects on presynaptic neurons, inhibiting subsequent synaptic transmission. Anandamide (means “eternal bliss”) o Soluble-gas neurotransmitters: produced in the neural cytoplasm and immediately diffuse through the cell membrane into the extracellular fluid and then into nearby cells. They easily pass through cell membranes because they are soluble in lipids. They stimulate the production of second messengers and are then deactivated by being converted to other molecules. Have been shown to be involved in retrograde transmission. At some synapses they transmit feedback signals from the post-synaptic neuron back to the presynaptic neuron, to regulate activity of presynaptic neurons. Nitric oxide Carbon monoxide (Large molecule) Neuropeptides: over 100 have been identified. They often function not only just as neurotransmitters o Pituitary peptides: neuropeptides that were first identified as hormones released by the pituitary o Hypothalamic peptides: neuropeptides that were first identified as hormones released by the hypothalamus o Brain-gut peptides: neuropeptides that were first discovered in the gut o Opioid peptides: neuropeptides that are similar in structure to the active ingredients of opium. All have metabotropic receptors. Enkephalins Endorphins o Miscellaneous peptides: catch-all category that contains all of the neuropeptide transmitters
4.7 Pharmacology of Synaptic Transmission and Behaviour Agonists: facility the effects of a particular neurotransmitter Antagonists: inhibit the effects of a particular neurotransmitter Receptor blockers: bind to postsynaptic receptors without activating them and block the access of the neurotransmitter Behavioural Pharmacology: Three Influential Lines of Research
