Bi 133-07-aggr=4-16_rd

Bi 133-07-aggr=4-16_rd - OUTLINE 1 Types of aggression...

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Unformatted text preview: OUTLINE 1. Types of aggression; anger vs. aggression 2. Aggression circuitry in mammals 1. Cats 2. Rodents AGGRESSION AND ANGER • What causes anger? – Panskepp: Interference with goal-directed behavior "frustration" • Is anger always expressed by aggression? • Types of aggression: – – – – – – 1 4/15/07 3. Neurochemistry of aggression 4. "Aggression genes" 5. Aggression in arthropods 4/15/07 Bi 133 D.J. Anderson Predatory aggression Defensive rage Inter-male (dominance) aggression Maternal aggression Anti-predator aggression Territorial aggression Bi 133 D.J. Anderson 2 FEATURES OF AGGRESSION • Almost of universal behavior of nonhermaphroditic metazoans • Under strong inhibitory control – Energetically costly, high-risk behavior – Typically used to defend territory, compete for mates or food STEREOTYPED BEHAVIORS REFLECTING ESCALATION OF AGGRESSION IN CRICKETS • Intensity of behavior reflects intensity of internal arousal state • Qualitative shifts in behavior occur as intensity of encounter escalates • Stereotyped behavior patterns 4/15/07 Bi 133 D.J. Anderson 3 4/15/07 Bi 133 D.J. Anderson 4 STIMULATION EXPERIMENTS IDENTIFY AREAS SUFFICIENT TO TRIGGER BEHAVIOR TWO TYPES OF AGGRESSION IN CATS "PREDATORY ATTACK" "PREDATORY "DEFENSIVE RAGE" "DEFENSIVE Hess, 1940's (cats) 4/15/07 Bi 133 D.J. Anderson 5 4/15/07 Bi 133 D.J. Anderson 6 1 CRITICAL BRAIN REGIONS INVOLVED IN AGGRESSION PERI-AQUEDUCTAL GRAY (PAG) HINDBRAIN HYPOTHALAMUS QUIET BITING AND DEFENSIVE RAGE ELICITED BY STIMULATION OF DISTINCT SITES IN THE HYPOTHALAMUS AND PAG Trigeminal motor Nucleus (V) Facial motor Nucleus (VII) MB VMH MPN Quiet biting Defensive rage Medial Hypothalamic Nuclei 7 4/15/07 Bi 133 D.J. Anderson 8 4/15/07 Bi 133 D.J. Anderson DEFENSIVE RAGE CIRCUIT IN THE CAT BRAIN PREDATORY ATTACK CIRCUIT IN THE CAT BRAIN 4/15/07 Bi 133 D.J. Anderson 9 4/15/07 Bi 133 D.J. Anderson 10 CIRCUITS THAT "MEDIATE" vs. CIRCUITS vs "MODULATE" AGGRESSIVE BEHAVIOR • Circuits that mediate behavior are Circuits mediate sufficient to elicit aggression when stimulated • Circuits that modulate aggression do Circuits modulate not by themselves elicit aggression, but change the threshold for eliciting aggression in mediating areas – Requires double-stimulation experiments 4/15/07 Bi 133 D.J. Anderson 11 OPPONENT CIRCUITS MODULATING PREDATORY ATTACK vs. DEFENSIVE RAGE ATTACK vs 4/15/07 Bi 133 D.J. Anderson 12 2 HYPOTHALAMIC ATTACK SITES IN THE RAT Partial Overlap Fight and Flight Area 4/15/07 Bi 133 D.J. Anderson 13 4/15/07 Bi 133 D.J. Anderson 14 PROJECTIONS OF HAA IN RAT DIFFERENCES BETWEEN BRAINSTIMULATION EVOKED AGGRESSION IN CAT vs. RAT AGGRESSION vs • Rat does not show distinct "predatory attack" vs. "defensive rage" circuits – Possibility 1: reflects real species difference in organization of attack circuitry – Possibility 2: spatial resolution of stimulation methods in smaller rat brain insufficient to discriminate *role of PAG unclear 4/15/07 Bi 133 D.J. Anderson 15 4/15/07 Bi 133 D.J. Anderson 16 BRAIN STIMULATION-EVOKED AGGRESSION IN THE RAT EVIDENCE FOR DISTINCT SITES FOR DIFFERENT ATTACK BEHAVIORS IN RAT 4/15/07 Bi 133 D.J. Anderson 17 4/15/07 Bi 133 D.J. Anderson 18 3 ISSUES IN BRAIN STIMULATIONEVOKED AGGRESSION • Is hypothalamus involved in producing emotional state of "anger" associated with defensive rage? – Studies from human stimulation experiments NEUROCHEMISTRY OF AGGRESSION IN MAMMALS 1 Serotonin (5-HT) Arginine vasopressin (AVP) Arginine vasopressin 5-HT 1B receptors V1A receptors • Are HAAs involved in natural aggressive Are involved behavior? – Lesion experiments (mostly old papers, electrolytic lesions) – Many hypothalamic lesions increase, rather than decrease, aggressiveness – Regional infusion of pharmacologic agents 4/15/07 Bi 133 D.J. Anderson 19 4/15/07 aggression • Where and how? Bi 133 D.J. Anderson 20 PAXIL BLOCKS THE ABILITY OF AVP INJECTION INTO AHN TO PROMOTE AGGRESSION MODEL FOR ANTAGONISTIC INTERACTION OF 5-HT AND AVP IN ANTERIOR HYPOTHALAMUS 5-HT terminals 4/15/07 Bi 133 D.J. Anderson AVP neuron 21 4/15/07 Bi 133 D.J. Anderson Ferris et al (1997) J. Neurosci Ferris Neurosci 17:4331 22 STEROID HORMONE PATHWAYS ANDROGENS AND ESTROGENS ARE ESSENTIAL FOR AGGRESSION castration RELEASING STIMULUS testosterone P450 aromatase AR ER (core pathway) estrogen AGGRESSIVE BEHAVIOR castration castration 4/15/07 Bi 133 D.J. Anderson 23 4/15/07 testosterone replacement testosterone replacement + aromatase inhibitors inhibitors Bi 133 D.J. Anderson aggression No aggression 24 4 "RESIDENT-INTRUDER" TEST OF AGGRESSIVENESS IN MICE ESTROGEN RECEPTOR ALPHA IS REQUIRED FOR MALE AGGRESSION Inter-male aggression *Erα mutant females are more aggressive are more than wild-type 4/15/07 Bi 133 D.J. Anderson 25 4/15/07 Bi 133 D.J. Anderson 26 ANDROGEN RECEPTOR EXPRESSION IS RESTRICTED TO CIRCUITS INVOLVED IN MATING AND AGGRESSION GENE KNOCKOUTS PRODUCING AGGRESSION PHENOTYPES IN MICE MeApv Shah, et al. (2004) Neuron 43:313 4/15/07 Bi 133 D.J. Anderson 27 4/15/07 Bi 133 D.J. Anderson 28 BIOGENESIS OF NO nNOS IS EXPRESSED IN MEA nNOS IS 4/15/07 Bi 133 D.J. Anderson 29 4/15/07 Bi 133 D.J. Anderson 30 5 INCREASED AGGRESSION OF nNOS KNOCKOUT INCREASED nNOS KNOCKOUT MICE DEPENDS ON GENETIC BACKGROUND SEPARATION OF OFFENSIVE AGGRESSION FROM PREDATORY ATTACK IN AVP1b RECEPTOR KNOCKOUT MICE Wersinger et al. (2006) Genes Brain Behav. Behav 4/15/07 Bi 133 D.J. Anderson 31 4/15/07 Bi 133 D.J. Anderson 32 GENE KNOCKOUTS PRODUCING AGGRESSION PHENOTYPES IN MICE MONOAMINE OXIDASE (MAO) AND AFFECTIVE DISORDERS MAO inhibitor MAO for depression for 4/15/07 Bi 133 D.J. Anderson 33 4/15/07 Bi 133 D.J. Anderson 34 A GENETIC ASSOCIATION BETWEEN MAO DEFICIENCY AND IMPULSIVE AGGRESSION IN HUMANS INTERACTION BETWEEN CHILDHOOD MALTREATMENT AND LOW MAO ACTIVITY IN A CORRELATION WITH VIOLENT BEHAVIOR …but: Science (1993) 262:578 4/15/07 Bi 133 D.J. Anderson 35 4/15/07 Bi 133 D.J. Anderson 36 6 ROLE OF PHEROMONES IN AGGRESSION TrpC2 IS REQUIRED FOR INTERMALE AGGRESSION TrpC2 Stowers et al. (2002) Science 295:1493 Stowers et 4/15/07 Bi 133 D.J. Anderson 37 4/15/07 Bi 133 D.J. Anderson 38 BEHAVIOR OF TRPC2 MUTANT MALES TrpC2+/- male + intruder TrpC2-/- male + intruder MODEL FOR ROLE OF VNO IN AGGRESSION 4/15/07 Bi 133 D.J. Anderson 39 4/15/07 Bi 133 D.J. Anderson 40 INVERTEBRATE AGGRESSION BIOGENIC AMINES 4/15/07 Bi 133 D.J. Anderson 41 4/15/07 Bi 133 D.J. Anderson 42 7 MONOAMINES CONTROL AGGRESSION POSTURES IN CRAYFISH serotonin octopamine AN EXTREME FORM OF SUBMISSION IN CRAYFISH 4/15/07 Bi 133 D.J. Anderson 43 4/15/07 Bi 133 D.J. Anderson 44 AGGRESSION IN DROSOPHILA AGGRESSION DROSOPHILA • • • Sturtevant H, 1915 Dow and Schilcher, 1975 Dow Schilcher Skrzipek et al, 1978 Skrzipek et MORE RECENT STUDIES OF FLY AGGRESSION • • • • Sturtevant H, 1915 Dow and Schilcher, 1975 Dow Schilcher Skrzipek et al, 1978 Skrzipek et Chen et al, 2002 Chen 2002 wing-threat fencing boxing tussling boxing/tussling 4/15/07 Bi 133 D.J. Anderson 45 4/15/07 Bi 133 D.J. Anderson 46 LOW-LEVEL AGGRESSION IN FLIES: LUNGING Lunging: one fly rears up on hind legs and snaps down on the other CONSTRUCTING AN ETHOGRAM FOR AGGRESSIVE BEHAVIOR IN FLIES Chen et al. (2002) PNAS 99:5664 4/15/07 Bi 133 D.J. Anderson Suse Hoyer/Martin Heisenberg Suse Hoyer/Martin 47 4/15/07 Bi 133 D.J. Anderson 48 Liming Wang 8 GENETICS OF AGGRESSION IN FLIES MUTATIONS IN TßH CHANGE THE MUTATIONS CHANGE BALANCE BETWEEN COURTSHIP AND AGGRESSION aggression courtship aggression courtship Fig. 1. Manipulating OCT levels and the sex of OCT/TYR neurons changes the usage of aggressive and courtship behaviors. (a and b) Graph depicting the percentage of aggression (black) and courtship (gray) transitions after a wing extension. Control males ( T hM6 and UAS- tra / ) predominantly transition to aggression (aggression/total transitions, n 31/37 and 20/23). Experimental males [ T hnM18 , T hMF372 , dTdc2-Gal4 ;UAS- tra, and dTdc2-Gal4 (new insertion #1);UAS- tra ] transition to aggression and courtship or predominantly to courtship (courtship/total transitions: n 24/42, 11/14, 24/31, and 30/39). The number of courtship vs . aggressive transitional patterns was comparedamong control and experimental genotypes with the Fisher exact probability test. Significant frequency differences were observed between T hM6 and T hnM18 patterns (P 0.0002), T hM6 and T hMF372 patterns (P 0.0006), and UAStra / and dTdc2-Gal4#1 ;UAS- tra patterns (P 0.000001). (c–e) A still frame series of a wing extension followed by an aggressive lunge behavior. Wing vibration is not visible at this resolution or in a single clip, but see SI Movies 1 and 2. The clips show a T hnM18 male approaching and starting a wing extension (c), continuing the wing extension ( d ), and demonstrating an aggressive lunge (e, arrow). ( f–h) A still frame series of courtship behavior after a wing extension. These individual clips also are of a T hnM18 male pair. One male is performing a wing extension and tapping ( f), followed by abdomenbending (arrow) (g), and the courting male is rejected by the courted male (wing flick), and the wing extension ends ( h) (see SI Movies 1 and 2). Certel et al. (2007) PNAS 14:4706 4/15/07 Bi 133 D.J. Anderson 49 4/15/07 Bi 133 D.J. Anderson 50 TßH IS EXPRESSED BY ONLY ~70 IS NEURONS IN THE FLY BRAIN GENETIC SELECTION OF FLIES FOR INCREASED AGGRESSIVE BEHAVIOR Gen 11 Gen Gen 21 Mixed pairs Dierick and Greenspan (2006) Nat. Genet. Dierick 4/15/07 Bi 133 D.J. Anderson 51 4/15/07 Bi 133 D.J. Anderson 52 IDENTIFICATION OF DIFFERENTIALLY EXPRESSED GENES IN MORE AGGRESSIVE FLIES BY MICROARRAY ANALYSIS Cyp620 mutants exhibit increased aggressiveness COMMONALITIES BETWEEN MOUSE AND DROSOPHILA AGGRESSION • Influence of biogenic amines (octopamine, serotonin) • Social isolation increases aggressiveness • Some manipulations that decrease aggressiveness increase male-male mating • Physical expression (chasing/boxing) • Rapid establishment of dominance hierarchies • Influence of genetic background 4/15/07 Bi 133 D.J. Anderson 53 4/15/07 Bi 133 D.J. Anderson 54 9 BIG UNANSWERED QUESTIONS • What is the neural basis of the subjective experience of "anger"? – Specific circuit activation; cortical involvement? – As-yet unknown hypothalamic neuropeptide? As-yet neuropeptide • How is aggressive behavior encoded in the genome? • Are the aggression circuits in the rodent brain really what we think they are? – General, distributed region for multiple kinds of aggressive behavior (HAA)? – Distinct circuits for different kinds of aggression that could be separated with higher-resolution methods? • Are there specific pheromones that trigger aggression in rodents? • Are there genetic polymorphisms or allelic variants that can predict future violent behavior in humans? 4/15/07 Bi 133 D.J. Anderson 55 10 10 ...
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This document was uploaded on 01/03/2012.

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