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Psych 7 Mascolo Course Notes – Neural Conduction & Transmission – Richard Mascolo, Ph.D. Chapter 4: Neural Conduction & Synaptic Transmission All cells carry an electrical charge, but neurons take advantage of this Neurons take advantage of this in order to conduct messages down their length and across to other neurons – their basic function. A neuron’s electrical charge is called electrochemical – like your car battery the charge is based in chemistry – charged ions that are unequally balanced across the cell membrane – that is, inside the cell (“intracellular”) versus outside the cell (“extracellular”) – that’s why it is called the membrane potential. To start, what exactly is an ion? Atoms with an unequal # of positively charged protons & negatively charged electrons. When # of protons > # of electrons, then the ion is positively charged. When # of protons < # of electrons, then the ion is negatively charged. Here are some examples we’ll be studying: Sodium (Na+) => 11 protons, 10 electrons – the “+” means 1 more proton than electron Potassium (K+) => 19 protons, 18 electrons – again, the “+” means 1 more proton than electron Calcium (Ca++ or Ca2+) => 20 protons, 18 electrons -- the “++” or “2+” means 2 more protons than electrons Chloride (Cl-) => 17 protons, 18 electrons – the “-“ means 1 more electron than proton Summary your text’s presentation (from the previous edition, but I like it): Psych 7 Mascolo Course Notes – Neural Conduction & Transmission – Richard Mascolo, Ph.D. I will focus on 2 particular ions -- Na+ & K+ -- & 4 basic factors that affect their intracellular and extracellular distributions when the neuron is inactive – its “Resting Potential”: #1 Na+ K+ #2 #3 #4 Differential Cell Membrane Sodium/Potassium Pump Concentration Gradient Electrostatic Pressure Hard to cross Easy to cross extracellular intracellular intracellular extracellular intracellular intracellular 3 of these factors are “passive” – that is, they do not require energy: #1 is a characteristic of the cell membrane itself – called “semipermeable”, the imbedded channel proteins are differentially permeable to different molecules. #3 is actually a physical force called diffusion – substances flow down their concentration gradient – that is, from areas of higher concentration to areas of lower concentration. #4 is also a physical force involving electrical charge – substances flow away from areas with the same electrical charge to areas with the opposite electrical charge. The last of these factors is “active” – that is, it does require energy: #2 is based on a particular channel imbedded in the cell membrane – just like #1 – but this one does require energy. This sodium-potassium pump in fact uses up 40% of the cell’s energy – an expensive little beast! It pumps 3 sodium ions out of the cell (efflux) for every 2 potassium ions into the cell (influx). This ratio of 3 positive ions out for every 2 positive ions in leads to a net negative charge of the cell. If not for the activity of the sodium-potassium pump, the other 3 factors would even out the distribution of sodium & potassium, and the cell would end up with no electrical charge. The sodium-potassium pump is an energy hog – evolutionary theory suggests there must be a big adaptive advantage to maintaining this resting potential of -70mV. A neuron receives messages from other neurons that alter its Resting Potential. The neuron that sends the message is called “presynaptic” – the neuron that receives the message is called “postsynaptic”. We are focusing now on the postsynaptic neuron -- its resting potential is altered in 1 of 2 different ways. This is called a Graded Potential (GP): EPSP “Excitatory Postsynaptic Potential” alters the resting potential by depolarizing the postsynaptic cell – that is, the resting potential is reduced from -70mV to, say, -68 mV. IPSP “Inhibitory Postsynaptic Potential” alters the resting potential by hyperpolarizing the postsynaptic cell – that is, the resting potential is increased from -70mV to, say, -73 mV. Psych 7 Mascolo Course Notes – Neural Conduction & Transmission – Richard Mascolo, Ph.D. The reason for the terms “Excitatory” & “Inhibitory” is that depolarization moves the postsynaptic cell closer to firing a message of its own – an explosive Action Potential (AP) -- but hyperpolarization moves the postsynaptic cell farther from firing an AP. The depolarization required to trigger an AP is called the “threshold of excitement” – it’s about +5mV – so the average neuron must depolarize from its resting potential of 70mV to -65mV in order to trigger an AP. All GPs – EPSPs & IPSPs – have these characteristics: their intensity can be anywhere between very strong & very weak – they are graded they are conducted so rapidly they can be considered instantaneous they lose strength as they are conducted – so they are decremental. The combined influences of various EPSPs and IPSPs gather at the Axon Initial Segment & determine whether or not the Postsynaptic Neuron fires an Action Potential Spatial Summation: Different presynaptic neurons create Graded Potentials on different places on the Postsynaptic Neuron -- these gather just below the Axon Hillock –first part of the Axon – the Axon Initial Segment Temporal Summation: One Presynaptic Neuron creates several Graded Potentials from one space on the Postsynaptic Neuron, & these gather at the Axon Initial Segment Conduction of Action Potentials Ionic Basis of Action Potentials Your text provides a detailed description of the step-by-step process of an AP. Once again, you can focus on the activities of 2 ions – sodium & potassium – the “voltage activated gates” that control their flow across the cell membrane. Basically, it is the influx of Sodium that causes the “Rising Phase” (depolarization), & it is the efflux of Potassium that causes the “Repolarization Phase” (hyperpolarization) Your text provides a Figure illustrating this process – including the actions of those voltage-activated gates – study it carefully Refractory Periods Absolute Refractory Period – 1-2 milliseconds after the axon fires an AP, it cannot fire another one. Relative Refractory Period – a few milliseconds later, this portion of the axon can fire another AP, but only if it is depolarized more intensely than usual (i.e., more than +5mV) Psych 7 Mascolo Course Notes – Neural Conduction & Transmission – Richard Mascolo, Ph.D. Axonal Conduction of Action Potentials Characteristic Voltage Activated Channels? Decremental Velocity Structures: Graded Potential (GP) Action Potential (AP) No – Passive Conduction Yes (Time & Distance) Instantaneous Dendrite & Soma Yes – Active Conduction No (Actively Regenerated) Slow Axon Conduction in Myelinated Axons The difference here is that axons with myelin sheath can conduct the AP by “skipping” between instantaneous conduction (like GPs) & slower regeneration (why APs are nondecremental) – the former occur under the fatty myelin, the latter occur at the Nodes of Ranvier. Synaptic Transmission Structure of Synapses: they are named after the part of the presynaptic neuron (dendrite, soma, or axon) and the part of the postsynaptic neuron that are joining together to form the synapse. Here are 3 examples (the first 2 are the most common): presynaptic axon joins a postsynaptic dendrite – thus: axodendritic presynaptic axon joins a postsynaptic soma – thus: axosomatic presynaptic axon joins a postsynaptic axon – thus: axoaxonic (this last one allows for presynaptic inhibition/facilitation—see Figure 4.8) Nondirected Synapses – see Figure 4.9 for an example Release of NT molecules: Exocytosis – the process by which NTs are ejected from the axon button • NT molecules are synthesized and packed into vesicles -- small molecule NTs right there in the terminal button and large molecule NTs in the cell soma (they have to be transported down the axon to the terminal button) – see your text for details – either way, they are ready for release. • Release is dependent upon the arrival of an AP, but neither sodium nor potassium is involved in the actual process – research has shown that when Na+ or K+ channels are blocked at the axon button, NT molecules are still released. • Instead, the arrival of an AP at the axon button causes Calcium channels to open; the influx of Ca++ is the direct cause of the exocytosis process – vesicles fuse with the cell membrane and empty their NT molecules into the synaptic cleft. (see Figure 4.10) Psych 7 Mascolo Course Notes – Neural Conduction & Transmission – Richard Mascolo, Ph.D. Activation of Postsynaptic Receptors by NT molecules: 2 Types of Receptors Ionotropic Receptors activate Ion Channels & so directly cause EPSPs or IPSPs. These effects are simple, quick, & brief. For example: Open Sodium Channels (Na+ influx) – EPSP • Open Potassium Channels (K+ efflux) – IPSP • Open Chloride Channels (Cl- influx) -- IPSP • Metabotropic Receptors are indirect – the NT cause a “2nd messenger” release inside the cell (e.g., a G protein). These effects are complicated, slow, & long-lasting NTs land on Postsynaptic Receptors for just a few milliseconds. After that, they are pulled back into the Presynaptic Neuron through 1 of 2 processes Reuptake – most common Enzygmatic Degradation – less common (e.g., ACh is broken down by the enzyme AChE) Recycling – either way, NTs are pulled back into the Presynaptic Neuron & are used again Glial Cells Revisited – there are many examples of neural structures credited with many more functions now than when I took this course! Glial cells may actually transmit information themselves. Gap Junctions – Since we’re on this topic of “exceptions”, I may as well acknowledge research showing that some synaptic junctions directly transmit electrical charges without the use of NTs. That’s all I’m going to say about this! Autoreceptors -- primarily Inhibitory – 1 of the 2 ways that Presynaptic Inhibition can occur Psych 7 Mascolo Course Notes – Neural Conduction & Transmission – Richard Mascolo, Ph.D. Types of Neurotransmitters (NTs) – listed in bold – • Amino Acids -- simple building blocks of proteins -- earliest & most prevalent • Glutamate -- most prevalent excitatory NT • GABA -- most prevalent inhibitory NT • Monoamines – Catecholamines (Tyrosine -- Amino Acid Precursor) (L-Dopa -- Precursor) Dopamine Norepinephrine Epinephrine Indolamine (Tryptophan--Amino Acid Precursor) Serotonin (5-HT) • Acetylcholine (ACh) • Unconventional NTs -- gases, endocannabinoids • Neuropeptides (Endorphins) Neurons are named after the NT they release: Cholinergic Neurons Dopaminergic Neurons Serotonergic Neurons Adrenergic Neurons Noradrenergic Neurons Release Release Release Release Release Acetylcholine Dopamine Serotonin Epinephrine (Adrenaline) Norepinephrine (Noradrenaline) How Drugs Influence Synaptic Transmission Figure 4.17 summarizes the steps involved in NT activity – from synthesis to deactivation. Figure 4.18 details 2 basic categories of drug action: Agonistic -- Mimic or intensify a NT effect • Antagonistic -- Impede or block a NT effect (e.g., Botox is a Nicotinic • antagonist)