Limbic system. Lecture 29, November 10, 2017
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1 Limbic system Lecture 29, November 10, 2017
2 Circadian rhythms (Latin, approximately a day ) Regulation of our daily rhythm Eating Sleeping Defecating Periods of activity Suprachiasmatic n.
3 Circadian pattern generation Suprachiasmatic nucleus (SCN) SMALL: only 10,000 neurons master clock SCN Optic chiasm
4 Intrinsic circadian rhythm runs slow Laboratory experiment; 20- y.o. male With no light cues, 25.3 hr sleep cycle Similar intrinsic rhythm also seen in SCN tissue slices Day Number Timing of sleep (hours) Slept when desired Awoken every 24 h Czeisler CA; Sleep. 4(1):1-21, 1981.
5 Setting the circadian beat Light sets the circadian clock Input from eyes: retino-hypothalamic pathway Light-sensitive retinal ganglion neurons SCN expresses melatonin receptors Melatonin is secreted by pineal Secretion increases at night
6 Limbic system
7 limbus : a border (around the diencephalon)
8 A definition of limbic system A set of interconnected brain regions that are involved in autonomic control, behavior, memory, emotion, and the integration of these functions
9 A definition of limbic system A set of interconnected brain regions that are involved in autonomic control, behavior, emotion, and the integration of these functions Limbic structures are interposed between neocortex and the hypothalamus
10 A definition of limbic system A set of interconnected brain regions that are involved in autonomic control, behavior, emotion, and the integration of these functions Limbic structures are interposed between neocortex and the hypothalamus Limbic system links motivation with behavior & autonomic control
11 Diencephalon Hypothalamus (parts) Mammillothalamic tract Thalamus (parts) Fornix (tract) Telencephalon Prefrontal cortex Cingulate cortex Hippocampus Septal nuclei Amygdala Nucleus accumbens Olfactory system Limbic regions
12 Limbic regions Cingulate gyrus Septal n. N. accumbens
13 Prefrontal cortex Limbic regions
14 More limbic regions Fornix Anterior n. thalamus Amygdala Hippocampus
15 Hippocampus: sea horse Lateral ventricle Dentate gyrus Hippocampus Parahippocampal gyrus
16 Mammillothalamic tract: from mammillary bodies to anterior n thalamus Anterior n thalamus Mammillothalamic tract Mammillary bodies
17 Papez circuit: basis of emotion?
18 Phenomena associated with limbic system Self-control, rage, & aggression Learning/memory Fear/emotion Addiction
19 Self-control, aggression & rage Septum Lesion septal rage in rats Pre-frontal cortex Stimulation in animals Suppresses predatory aggression & defensive rage Lesions (e.g., pre-frontal lobotomy) Decreased aggressiveness in some psychotic patients Increased feeding Decreased intellectual function in some tests
20 Altered cingulate connections in psychopaths Philippi et al. J Neuroscience 35(15):6068, 2015 Antisocial traits in psychopathic prison inmates correlated with decreased connectivity between cingulate & other brain regions
21 Self-control: the case of Phineas Gage Foreman on railroad crew in 1848, supervising blasting with black powder 1.05 meter-long tamping rod blown through left cheek & out top of head. He survived. Damage to prefrontal cortex and anterior cingulate gyrus
![Gage s injury: current estimate Polygon data is generated by Database Center for Life Science(DBCLS)[3]. - Ratiu P, Talos IF, Haker S, Lieberman D, Everett P.](/docs-images/82/86611520/images/22-0.jpg "The tale of Phineas Gage, digitally remastered. J Neurotrauma. 2004 May;21(5):637-43. PMID: 15165371 [1]Polygon data is from BodyParts3D[2]., CC BY-SA 2.1 jp, https://commons.wikimedia.")
22 Gage s injury: current estimate Polygon data is generated by Database Center for Life Science(DBCLS)[3]. - Ratiu P, Talos IF, Haker S, Lieberman D, Everett P. The tale of Phineas Gage, digitally remastered. J Neurotrauma May;21(5): PMID: [1]Polygon data is from BodyParts3D[2]., CC BY-SA 2.1 jp,
23 Results of Gage s injury Profound personality changes Before Hardworking Responsible Well thought-of After Little self-restraint Irresponsible & short-sighted; moved from job to job Tactless & profane [He] is no longer Gage Suggested a role for pre-frontal cortex in self-control
24 Phineas Gage: aftermath of injury Eventually appears to have recovered selfcontrol Held steady job as stagecoach driver Died 12 years later of seizure disorder Any hypotheses for mechanism of recovery? What might this say about the anatomy underlying self-control?
25 Limbic system, learning and memory Amygdala Hippocampus
26 Patient H.M. Lesions of medial temporal lobe disrupt consolidation of memory Patient H.M.: temporal lobe epilepsy Treated by bilateral lesion of medial temporal lobe, affecting amygdala & part of the hippocampus Unable to lay down new long-term declarative memory (e.g., names; dates) after surgery No loss of long-term memory from pre-surgery Motor memory ( procedural memory ) unimpaired Intellectual ability unimpaired
27 Limbic system, learning & memory Other limbic-system lesions also disrupt consolidation of long-term memory Korsakoff syndrome: damage from alcoholism to mammillary bodies & thalamus Inability to form new declarative memory Confabulation : will create a plausible story if they don t remember the answer to a question Damage may be due to alcoholic malnutrition
28 Papez circuit and memory Hippocampus (via fornix) Mammillary bodies (via mammillothalamic tract) Anterior nucleus of thalamus Cingulate cortex
29 Long-term potentiation (LTP)& memory: increase in synaptic efficacy from use Ca ++ AMPAr phosphorylation activation Ca ++ ERK phosphorylation AMPAr gene expression
30 Amygdala, fear & emotion Stimulation of amygdala attention (animals) or fear (humans) Increased activity of amygdala in humans with anxiety Bilateral amygdala damage No conditioning to aversive stimuli No recognition of fearful faces Kluver-Bucy syndrome: lesions to entire temporal lobe other than auditory cortex Animals are unresponsive to possible & actual threats
31 Nature Neuroscience (3): 270 Humans: Urbach-Wiethe disease (U-W) bilateral loss of amygdala loss of fear However, breathing C0 2 fear/panic in U-W patients Sensation of fear/panic not necessarily localized to amygdala
32 Amygdala & recognition of emotion without awareness Pegna et al, Nature Neuroscience 8: 24-25, 2005
33 Addiction & nucleus accumbens Oberlin et al., Psychopharmacology. 232(5):861-70, 2015 Addictive drugs produce dopamine release in n. accumbens Ethanol Cocaine Heroin Methamphetamine
34 Addiction & nucleus accumbens Naturally pleasant activities also cause dopamine release in n. accumbens Eating Sex Exercise etc.
35 Addiction & nucleus accumbens Nucleus accumbens appears to be a structure underlying natural reward Addictive drugs appear to hijack the reward system Positive reward from drug use Negative reward from drug abstinence.
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