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MOLECULES and BEHAVIOR 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Motivation Reward Depression Anxiety Stress Schizophrenia TOC-Compulsive Disorder ADHD-Attention Deficit Hyperactivity Disorder Aggressivity Mood Disorders 1 MOLECULES and BEHAVIOR 1. Motivation a. b. c. d. 2. 3. 4. 5. 6. 7. 8. 9. 10. Generalities: the Brain - the Neuron - Neurotransmitters Brain and Behavior Motivation Theories - Self-motivation - Motivation and Learning Types of Learning - Motivation and Memory Reward Depression Anxiety Stress Schizophrenia TOC-Compulsive Disorder ADHD-Attention Deficit Hyperactivity Disorder Aggressivity Mood Disorders The Brain 2 The Brain The Brain • Cerebral Cortex – thought, language, reasoning, movement, sensation • Corpus Callosum – connects the right and left hemispheres • Cerebellum – movement, balance • Brainstem – breathing, heart rate 3 Lobes of the Brain hippocampus PLAN ACTION LEARN MEMORY GOAL DIRECTED BEHAVIOR OPTIMAL STIMULI RESPONSE AFFECT amygdala 4 The Neuron • The brain’s most basic functional unit The Neuron Soma Dendrites Myelin Sheath Axon Axon Terminals 5 The Neuron • Soma (cell body) – contains nucleus, cytoplasm, organelles • Dendrites – receive info • Axon – transmits info • Myelin sheath – covers the axon to increase transmission speed (cause of sensory and motor disturbances in multiple sclerosis) Action Potentials 6 Action Potentials • • • • • • • How neurons transfer info Changes neuron’s membrane potential Rising phase – membrane depolarizes Overshoot Falling phase – membrane repolarizes Undershoot Restoration of resting potential The Synapse 7 The Synapse • Axon terminal releases neurotransmitters • Neurotransmitters cross the synapse and bind to receptors on another neuron • Neurotransmitters released, taken up again by first neuron Neurotransmitters • Acetylcholine – movement (respiratory paralysis) • Serotonin – mood, sleep, appetite, anxiety (depression, obsessive-compulsive disorder, panic disorder) • Dopamine – motivation, pleasure (schizophrenia, Parkinson’s) • Epinephrine and Norepinephrine – attention, anxiety, stress (epilepsy, mania in bipolar disorder) 8 neurotransmitter criteria According to classical definitions, what criteria must be met in order to claim that a substance serves as a neurotransmitter? 1) Substance is present in nerve cell, specifically at the terminal 2) Cell can synthesize or accumulate the substance 3) Substance is released from nerve terminal in activity- and Ca2+-dependent fashion 4) Substance mimics functional activity seen following nerve cell stimulation (in magnitude and quality). 5) Drugs that simulate/antagonize effects of nerve cell activation have identical effects on exogenously applied substance. 6) Active mechanism for terminating action of the substance (e.g. enzymatic degradation, uptake) Main Neurotransmitters ⇒ Biogenic amines (classical neurotransmitters) catecholamines (dopamine, norepinephrine and epinephrine) serotonin (5-HT) histamine ⇒ Acetylcholine ⇒ Purinergic transmitters (ATP, UTP, adenosine) ⇒ Amino acid transmitters Glutamate (aspartate) GABA, glycine ⇒ Peptide neurotransmitters (a huge and growing list) ⇒ Unconventional transmitters (nitric oxide, carbon monoxide) 9 types of receptors ionotropic receptors the receptor itself incorporates an ionophore (ion channel), the gating of which is allosterically regulated by agonist binding to the receptor metabotropic receptors the receptor signals via intracellular intermediates to effect a change in ion channel gating, cell excitability, metabolic state or gene expression catalog of receptors ionotropic receptors metabotropic receptors 10 why are there so many flavors of transmitter and receptor? 1) Chemical coding of inputs can be used to distinguish among different afferents 2) Differential release depending on presynaptic activity pattern alter qualitatively the postsynaptic response as a function of presynaptic activity pattern why are there so many flavors of transmitter and receptor? 3) Allow summation of effects from different afferents 4) Allow effects in different time domains fast ionotropic effects slower metabotropic effects 5) Allow effects in different spatial domains e.g. peptides can diffuse away from release sites and interact with very high affinity receptors 11 Precursor Synthesis Storage = vesicle = neurotransmitters = receptor Degradation Reuptake Release Synaptic Cleft 12 dopamine transporters 13 Neuropharmacology Reuptake Inhibitors • Prevent reuptake of neurotransmitters from the synapse • Selective serotonin reuptake inhibitors • Example: Prozac< – Treats depression, OCD, panic disorder 14 Brain and Behavior Brain and Behavior • Unlikely to be a center in the brain causing a single behavior (eg. bulimia, anorexia) • Behavior combination of multiple “traits” • Gene differences can alter temperament “traits” and brain chemistry • How do we figure out what is a trait? – Do they occur before someone develops a certain pathological behavior ? – Do they persist after recovery from pathology? – Do they run in families? • How does temperament become an illness? 15 DOES THE BRAIN CODE BEHAVIOR? • OLD: Syndromes – collection of symptoms – anorexia, bulimia, depression, anxiety • NEW: Behavioral Economics – Assess stimuli – Compare to past memories – Choose appropriate response, consider short and long term consequences – Action – Assess effect of action – Learn from experience What Is Motivation? Direction Intensity Prentice Hall, 2001 Persistence Chapter 6 32 16 What Is Motivation? I was saying "I'm the greatest” long before I believed it. Intensity What Is Motivation? Direction Intensity 17 What Is Motivation? Direction Intensity It's not that I'm so smart, it's just that I stay with problems longer. Persistence Theories of Motivation Needs theories • Maslow’s hierarchy of needs • Herzberg’s two factor theory Process theories • Expectancy Theory • Goal Setting Theory 18 Needs Theories Needs theories • Maslow’s hierarchy of needs • Herzberg’s two factor theory Maslow Herzberg Self-Actualisation Motivators Esteem Social Safety Hygiene Factors Physiological Contrasting Views of Satisfaction and Dissatisfaction Traditional view Satisfaction Dissatisfaction Herzberg's view Motivators Motivators Satisfaction Herzberg No satisfaction Hygiene Factors No dissatisfaction Dissatisfaction Hygiene Factors 19 Expectancy Model of Motivation Effort Effort Performance Perceived effort performance probability Perceived performance reward probability Perceived value of reward “What rewards will I get when the job is well done?” “What rewards do I value?” “If I work hard, will I get the job done?” Reward Expectancy Model of Motivation Individual Effort 1 Individual Performance 2 Organisational Rewards 3 1. Effort-Performance relationship = Expectancy 2. Performance-Rewards relationship = Instrumentality Personal Goals 3. Rewards-Personal goals relationship = Valence Prentice Hall, 2001 Chapter 6 40 20 Expectancy Model of Motivation How Expectancy Theory Works Your tutor offers you £1 million if you memorise the textbook by tomorrow morning. Expectancy Instrumentality Effort - Performance Link Performance - Rewards Link No matter how much effort you put in, probably not possible Valence Your tutor does not look Rewards - Personal Goals Link There are a lot of wonderful things like someone who has £1 million you could do with £1 million I=0 V=1 to memorise the text in 24 hours E=0 Conclusion: Though you value the reward, you will not be motivated to do this task. Goal Setting Goals Specific Difficult Accepted Effects on Person Directs attention Energises Encourages persistency New strategies developed Performance Feedback 21 Self-Motivation • Self-fulfilment and satisfaction • Difficult goals lead to higher performance • Motivation to act depends on the attractiveness of the outcome Goals Specific Difficult Accepted Effects on Person Directs attention Energises Encourages persistency New strategies developed Performance Feedback Motivation 22 How can satisfaction and its linkage with performance help tie together insights of the motivation theories into an integrated motivational model? Work effort needed Organizational support Amount & schedule of contingent extrinsic rewards Equity comparison Net amount of valent intrinsic rewards Satisfaction Motivation Individual attributes Performance An Integrated Model of Individual Motivation to Work Experience is based on Reward •a positive experience induces reinforcemement • and leads to habit 23 a REWARD induces Positive Emotional Response acts as a REINFORCER or GOAL prevents EXTINCTION of a habit EFFORTFUL Response arises through Learning WHAT is REWARD ENVIRONMENT INSTINCT PROCESSING IMAGERY PERCEPTION MEMORY ANTICIPATION of PLEASURE AROUSAL MOTIVATION COMPLEX BEHAVIOR (feeding, HABITS sex, learning, etc) 24 Natural Rewards Elevate Dopamine Levels % of Basal DA Output NAc shell 150 100 50 Empty Box Feeding SEX 200 150 100 15 10 5 0 0 0 60 120 Time (min) Di Chiara et al., Neuroscience, 1999. 180 Copulation Frequency DA Concentration (% Baseline) FOOD 200 Female Present Sample Number 1 2 3 4 5 6 7 8 Mounts Intromissions Ejaculations Fiorino and Phillips, J. Neuroscience, 1997. Increase in DA in nucleus accumbens induced by food and by amphetamines as assessed by microdialysis in rodents Volkow and Wise 2005 25 Brain Reward Center - Dopamine D2 Receptors are Lower in Addiction Volkow et al DA DA DA DA DA DADA DA D2 Receptor Availability Cocaine Alcohol Heroin DA DA DA DA DA Reward Circuits Non-Drug Abuser DA DA DA DA DA DA Reward Circuits control addicted Drug Abuser The Reward Pathway Sustains life through pleasure Activated by pleasurable experience Food - sex - learning - etc Dopaminergic Major Anatomical Structure 26 • DA neurons are activated to perform certain behavior –motivational stimuli –motivational learning –reward prediction Activity in a DA neuron during a task DA Neuron are activated immediately before delivery of a reward, whether a movement is required or not, but are not activated in unrewarded trials 1. DA neurons respond to unpredictable rewards and produce a global reinforcement signal 2. Some neurons also react to the expectation & detection of reward. 3. Other neurons show reward-related activities related to the preparation, initiation execution of movement. Learning Theories How do we know what we know? - What do we mean by “learning”? we say that we have learnt something, if our experiences result in a change of our behaviour or our capabilities. “We learn by association. Our minds naturally connect events that occur in sequence.” This process of learning associations = “Conditioning” classical conditioning instrumental learning or operant conditioning Observational Learning 27 Learning Theories • Nonassociative Learning – Habituation – Sensitization • Classical Conditioning • Instrumental Learning • Observational Learning Reinforcement theories how are they linked to motivation? Reinforcement. – The administration of a consequence as a result of a behavior. – Proper management of reinforcement can change the direction, level, and persistence of an individual’s behavior. 28 Reinforcement theories how are they linked to motivation? Classical conditioning. – A form of learning through association that involves the manipulation of stimuli to influence behavior. – Involves an initial stimulus (unconditioned stimulus) and a conditioned stimulus in the learning of behavior. Reinforcement theories how are they linked to motivation? The classical conditioning process. – Behavior is caused by an unconditioned stimulus. – A conditioned stimulus is paired with the unconditioned stimulus. – The conditioned stimulus is able to evoke the behavior. 29 •Tone comes to produce same response as food. 30 Classical conditioning Discrimination Learning Discriminative Schedule – present 2 distinct stimulis CS+ 8,000 Hz tone (reinforced) CS- (not) Stimulus Generalization – tendency to respond to similar stimuli Discrimination training increases weights between CS+ & CR, increases inhibition between CS- and CR 31 Reinforcement theories how are they linked to motivation? Operant conditioning. – The process of controlling behavior by manipulating its consequences. – Focuses on the interplay of antecedents, behavior, and consequences. Reinforcement theories how are they linked to motivation? Antecedents – The condition leading up to or cueing behavior Behavior – The action taken by the person Consequences – The outcome received by the person 32 Operant Conditioning How animals learn to solve Problems (Thorndike, 1898) Example : place a hungry animal in a cage, which opens by pressing a lever. Outside the cage there is food. On successive trials the animal became quicker at opening the cage door (= instrumental learning or operant conditioning) the animals behaviour is instrumental for bringing about a certain outcome. Skinner’s experiments (Skinner box) Chamber with metal flooring and a lever connected to a food dispenser. The metal floor enables the administration of an electric shock, whereas pressing the lever releases a food pellet. if a lever press resulted in the release of a food pellet, the rats’ “response” would soon increase in frequency. Thus the lever pressing was reinforced. If the press of the lever is punished with the delivery of an electric shock, the animals’ response frequency would soon decrease. Operant Conditioning Instrumental Learning Instrumental Learning Reinforcement Operant Behaviors Skinner Box 33 Mixtures of Classical and Instrumental Conditioning • Both Occur Simultaneously • Instrumental (operant) conditioning ResponseReward contingency – but, Stimulus-Reward contingency is also being tracked • Autoshaping – suggests, stim-reinforcer relations inevitably present when response-reinforcer relations present Observational Learning How do we learn how to write, drive a car read,…? Classical and Operant conditioning would be tedious ways of learning such complex behaviours. It is easier to observe someone and then imitate what they did = observational learning Especially humans are extremely efficient at this type of learning because we are able to use language in addition. Similar to Classical and Operant conditioning it has important adaptive functions. 4 components: Attention Retention = Remember what you want to imitate. Reproduction = Imitation of behaviour. Motivation = Incentive for imitating behaviour 34 Learning and Memory Learning = Acquisition of knowledge or skills through experience and / or instruction. Memory = The storage of acquired knowledge for later recall. The basis for learning and memory is achieved through: • changing the effectiveness of a synapse • developing new synapses. Learning and Memory Types of learning 1. Habituation – a decrease in response occurring from repeated stimulation 2. Sensitization – an increase in response after experience of an unpleasant stimulus 3. Classical conditioning – an association of two stimuli, expecting one with the other 35 Learning and Memory MEMORY : the Hippocampus We have two types of memory: Short Term and Long Term Important for formation of short term memory Important for transferring short term memory to long term memory Types of Memory “primary” short-term working memory episodic memory [declarative, explicit] “secondary” long-term semantic memory procedural memory [non declarative, implicit] 36 Discriminative Learning Role of the Accumbens Stages of conditioned taste aversion learning (CTA) 1. 2. 3. 4. Consistently with its evolutionary significance of avoiding harmful foods, CTA takes place in relation to the consequences of the digestion and absorption of food contents. To allow sufficient time for these processes to be completed, a short-term memory trace of the salient gustatory stimulus has to be formed and stored to be later associated with the outcome of feeding. Blockade of D1 DA receptors impairs consolidation of the gustatory trace. Thus, the gustatory trace is weakened and eventually lost before an association between the representation of the gustatory stimulus and the aversive visceral state is made. By this mechanism, the whole associative learning process is impaired. Hypothesis on the Neural Substrate of Memory genomic level changes in genes associated with plasticity cellular level changes in the connections between neurons [synaptic plasticity] neural ensemble level behavioral level changes in the dynamics of neuronal groups [metaplasticity, maps] behavioral changes associated with learning and memory Do causal links exist between the different levels? 37 Short Term Memory Short Term Memory involves changing the effectiveness of a synapse. (Strengthening or Weakening of synapses) In a simplistic way this means that either less or more neurotransmitter is released from a synapses or synapses following a repeated stimulus. It all requires CALCIUM IONS •Habituation (decreased neurotransmitter release) •Sensitization •Long Term Potentiation (increased neurotransmitter release) Long Term Memory Involves protein synthesis Formation of new dendritic ‘spines’ (increased surface area) Formation of new synapses 38 Long Term Memory Dendrites Dendritic Spines Long Term Memory 39 Basal Ganglia The medial caudate and nucleus accumbens receive their input from frontal cortex and limbic areas The caudate and putamen are reciprocally interconnected with the substantia nigra (SNr-SNc) The caudate and the putament send most of their output to the globus pallidus (Gpe-Gpi) The globus pallidus can also be divided into two parts: the globus pallidus externa (GPe) and the globus pallidus interna (GPi). Both receive input from the caudate and putamen, and both are in communication with the subthalamic nucleus (STN). Basal Ganglia 40 GABA and Glutamate Role in Motivation Basolateral Amygdala Nucleus Accumbens Prefrontal Cortex Ventral Pallidum Dopamine Ventral Tegmental Area Mediodorsal Thalamus Motor Nuclei GABA Glutamate Adapted from Kalivas and Nakamura, Curr. Opin. Neurobiol., 1999. Reading 41