Prepared by Jeffrey W. Grimm Western Washington University PowerPoint Presentation for Biopsychology, 8th Edition by John P.J. Pinel Prepared by Jeffrey W. Grimm Western Washington University This multimedia product and its contents are protected under copyright law. The following are prohibited by law: any public performance or display, including transmission of any image over a network; preparation of any derivative work, including the extraction, in whole or in part, of any images; any rental, lease, or lending of the program. Copyright © 2011 Pearson Education, Inc. All rights reserved.

How Neurons Send and Receive Signals Chapter 4 Neural Conduction and Synaptic Transmission How Neurons Send and Receive Signals Copyright © 2011 Pearson Education, Inc. All rights reserved.

Resting Membrane Potential Recording the membrane potential: difference in electrical charge between inside and outside of cell Inside of the neuron is negative with respect to the outside Resting membrane potential is about –70mV Membrane is polarized (carries a charge) Copyright © 2011 Pearson Education, Inc. All rights reserved.

Ionic Basis of the Resting Potential Factors contributing to even distribution of ions (charged particles) Random motion – particles tend to move down their concentration gradient Electrostatic pressure – like repels like, opposites attract Factors contributing to uneven distribution of ions Selective permeability to certain ions Sodium-potassium pumps Copyright © 2011 Pearson Education, Inc. All rights reserved.

Ions Contributing to Resting Potential Sodium (Na+) Chloride (Cl-) Potassium (K+) Negatively charged proteins (A-) Synthesized within the neuron Found primarily within the neuron Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. The Neuron at Rest Ions move in and out through ion-specific channels K+ and Cl- pass readily Little movement of Na+ A- don’t move at all, trapped inside Copyright © 2011 Pearson Education, Inc. All rights reserved.

The Neuron at Rest Continued Equilibrium Potential (Hodgkin-Huxley model) The potential at which there is no net movement of an ion – the potential it will move to achieve when allowed to move freely Na+ = 120mV K+ = 90mV Cl- = -70mV (same as resting potential) Copyright © 2011 Pearson Education, Inc. All rights reserved.

The Neuron at Rest Continued Na+ is driven in by both electrostatic forces and its concentration gradient K+ is driven in by electrostatic forces and out by its concentration gradient Cl- is at equilibrium Sodium-potassium pump – active (uses ATP) force that exchanges 3 Na+ inside for 2 K+ outside Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 4.2 The passive and active factors that influence the distribution of Na+, K+, and Cl- ions across the neural membrane. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Generation and Conduction of Postsynaptic Potentials (PSPs) Neurotransmitters bind at postsynaptic receptors These chemical messengers bind and cause electrical changes Depolarizations (making the membrane potential less negative) Hyperpolarizations (making the membrane potential more negative) Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 4.3 An EPSP, and IPSP, and an EPSP followed by a typical AP. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. EPSPs and IPSPs Travel passively from their site of origination Decremental (graded) – they get smaller as they travel Copyright © 2011 Pearson Education, Inc. All rights reserved.

Integration of PSPs and Generation of Action Potentials (APs) One EPSP typically will not suffice to cause a neuron to “fire” and release neurotransmitter – summation is needed In order to generate an AP (or “fire”), the threshold of activation must be reached near the axon hillock Integration of IPSPs and EPSPs must result in a potential of about -65mV in order to generate an AP Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Integration Adding or combining a number of individual signals into one overall signal Spatial summation – integration of events happening at different places Temporal summation – integration of events happening at different times Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 4.4 The three possible combinations of spatial summation. FIGURE 4.5 The two possible combinations of temporal summation. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Conduction of APs All-or-none – when threshold is reached the neuron “fires” and the action potential either occurs or it does not When threshold is reached, voltage-activated ion channels are opened Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 4.6 The opening and closing of voltage-activated sodium and potassium channels during the three phases of the action potential: rising phase, repolarization, and hyperpolarization. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Refractory Periods Absolute – impossible to initiate another action potential Relative – harder to initiate another action potential Prevent the backwards movement of APs and limit the rate of firing Copyright © 2011 Pearson Education, Inc. All rights reserved.

PSPs vs. Action Potentials (APs) EPSPs/IPSPs Decremental Fast Passive (energy is not used) Action Potentials Nondecremental Conducted more slowly than PSPs Passive and active (use ATP) Copyright © 2011 Pearson Education, Inc. All rights reserved.

Axonal Conduction of APs Passive conduction (instant and decremental) along each myelin segment to next node of Ranvier New action potential generated at each node In myelinated axons: instant conduction along myelin segments results in faster conduction than in unmyelinated axons Copyright © 2011 Pearson Education, Inc. All rights reserved.

Velocity of Axonal Conduction Maximum velocity of conduction in human motor neurons is about 60 meters per second Copyright © 2011 Pearson Education, Inc. All rights reserved.

Conduction in Neurons without Axons Conduction in interneurons is typically passive and decremental Copyright © 2011 Pearson Education, Inc. All rights reserved.

The Hodgkin-Huxley Model in Perspective This model was based on squid motor neurons Cerebral neurons behave in ways that are not always predicted by the model Copyright © 2011 Pearson Education, Inc. All rights reserved.

Snaptic Transmission: Structure of Synapses Axodendritic are most common; axons synapse onto dendritic spines Directed synapse: site of release and contact are in close proximity Nondirected synapse: site of release and contact are separated by some distance Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 4.8 The anatomy of the typical synapse. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Synthesis, Packaging, and Transport of Neurotransmitter Molecules Small Synthesized in the terminal button and packaged in synaptic vesicles Large Assembled in the cell body, packaged in vesicles, and then transported to the axon terminal Copyright © 2011 Pearson Education, Inc. All rights reserved.

Release of Neurotransmitter (NT) Molecules Exocytosis – the process of NT release The arrival of an AP at the terminal opens voltage-activated Ca2+ channels The entry of Ca2+ causes vesicles to fuse with the terminal membrane and release their contents Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 4.11 Schematic and photographic illustrations of exocytosis. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Activation of Receptors by NT Molecules Released NT molecules produce signals in postsynaptic neurons by binding to receptors Receptors are specific for a given NT Ligand – a molecule that binds to another A NT is a ligand of its receptor Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Receptors There are multiple receptor types for a given NT Ionotropic receptors – associated with ligand-activated ion channels Metabotropic receptors – associated with signal proteins and G proteins Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Ionotropic Receptors NT binds and an associated ion channel opens or closes, causing a PSP If Na+ channels are opened, for example, an EPSP occurs If K+ channels are opened, for example, an IPSP occurs Copyright © 2011 Pearson Education, Inc. All rights reserved.

Metabotropic Receptors Effects are slower, longer-lasting, more diffuse, and more varied (1) NT 1st messenger binds. (2) G protein subunit breaks away. (3) Ion channel opened/closed OR a 2nd messenger is synthesized. (3) 2nd messengers may have a wide variety of effects. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 4.12 Ionotropic and metabotropic receptors. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Reuptake, Enzymatic Degradation, and Recycling As long as NT is in the synapse, it is “active” – activity must somehow be turned off Reuptake – scoop up and recycle NT Enzymatic degradation – a NT is broken down by enzymes Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 4.13 The two mechanisms for terminating neurotransmitter action in the synapse: reuptake and enzymatic degradation. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Glial Function and Synaptic Transmission Astrocytes appear to communicate and to modulate neuronal activity Some communication is through gap junctions between cells Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 4.14 Gap junctions. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Amino Acid Neurotransmitters Usually found at fast-acting directed synapses in the CNS Glutamate – Most prevalent excitatory neurotransmitter in the CNS GABA Synthesized from glutamate Most prevalent inhibitory NT in the CNS Aspartate and glycine Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Monoamines Effects tend to be diffused Catecholamines – synthesized from tyrosine Dopamine Norepinephrine Epinephrine Indolamines – synthesized from tryptophan Serotonin Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Acetylcholine Acetylcholine (Ach) Acetyl group + choline First identified at neuromuscular junction Copyright © 2011 Pearson Education, Inc. All rights reserved.

Unconventional Neurotransmitters Soluble gases – exist only briefly Nitric oxide and carbon monoxide Retrograde transmission – backwards communication Endacannabinoids anandamide is one of the two known endocannabinoids Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. Neuropeptides Large molecules Example – endorphins “Endogenous opioids” Produce analgesia (pain suppression) Receptors were identified before the natural ligand was Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 4.18 Seven steps in neurotransmitter action. Copyright © 2011 Pearson Education, Inc. All rights reserved.

Pharmacology of Synaptic Transmission How drugs influence synaptic activity Agonists – increase or facilitate activity Antagonists – decrease or inhibit activity A drug may act to alter neurotransmitter activity at any point in its “life cycle” Copyright © 2011 Pearson Education, Inc. All rights reserved.

Behavioral Pharmacology: Three Influential Lines of Research Drugs selective to specific receptor subtypes may exert different effects e.g. nicotinic vs. muscarinic acetylcholine receptors Discovery of the endogenous opioids provided insight into brain mechanisms of pleasure and pain Effects of dopamine agonists and antagonists on psychotic symptoms led to new treatments for schizophrenia Copyright © 2011 Pearson Education, Inc. All rights reserved.

Copyright © 2011 Pearson Education, Inc. All rights reserved. FIGURE 4.19 Some mechanisms of agonistic and antagonistic drug effects. Copyright © 2011 Pearson Education, Inc. All rights reserved.