Limbic System lecture, 2008

Amygdala and Hippocampus and Hypothalamus

Maryann Martone, Ph. D.

NEU257

The Limbic System

•Broca, Papez, Kluver and Bucy, McClean

•Parts of the brain underlying emotional behavior

•Associated with the olfactory system; rhinencephalon = “smell brain”

•“Often, the term “limbic” structure is used in a vague fashion to distinguish it from motor structures…” Heimer, 1996

“The hypothalamus, the anterior thalamic nucleus, the cingulate gyrus, the hippocampus and their interconnections, constitute a harmonious mechanism which

may elaborate the functions of central emotion as well as participate in the emotional expression.” -James Papez, 1939

http://www.hallym.ac.kr/~de1610/nana/chp-12n.htm#II

Limbic Lobe: Broca

From the Digital Anatomist website

Olfactory System

From the Digital Anatomist website

thalamus.wustl.edu/ course/lim5.gif

http://da-atlases.biostr.washington.edu:80/cgi-bin/DA/PageMaster?atlas:NeuroSyllabus+ffpathIndex/Syllabus^Chapters/VisceralAfferent/OlfSystem+2

Olfactory Cortex

•Pyriform cortex = 1˚ olfactory cortex

•Allocortex, paleocortex

•3 layeredhttp://da-atlases.biostr.washington.edu:80/cgi-bin/DA/PageMaster?atlas:NeuroSyllabus+ffpathIndex/Syllabus^Chapters/VisceralAfferent/OlfRegions+2

•Also cortical amygdaloid nucleus and periamygdaloid area

•Projects to ventral striatum, MD thalamus, insula and orbitofrontal cortex

Olfactory Cortex

http://www.hallym.ac.kr/~de1610/nana/chp-12n.htm#II

Olfactory Cortex

Monkey brainFrom the Digital Anatomist website

Rodent Brain

The Amygdala

• Burdach 1819: the amygdaloid complex (“almond”)

• Johnston 1923: central, medial, cortical, basal nuclei

• Price 1980’s: basolateral, cortical, central medial nucleus

• De Olmos and Heimer 1991: extended amygdala• Swanson 1998: there is no amygdala

The amygdaloid complex• Over 20 divisions/nuclei, depending on whom you talk to• 500-1000 different connections identified (Swanson)

• Swanson: “The amygdala is neither a structural nor a functional unit of the cerebral hemispheres; instead, its cell groups participate in at least four distinct, though interconnected, functional systems or differentiations of the corticostriatopallidal system…. Terms such as 'amygdala' and 'lenticular nucleus' combine cell groups arbitrarily rather than according to the structural and functional units to which they now seem to belong..”

» L. W. Swanson: The amygdala and its place in the cerebral hemisphere, PNAS 985: 174, 2003.

Human (from digital anatomist)

Macaque (from brainmaps.org)

Mouse

One view(based on Heimer, 1996)

• Basolateral– Similar to cortex– Projects to ventral striatum– Has pyramidal like cells– Receives input from primary sensory cortex, polysensory cortex and thalamus– Connections are reciprocal

• Cortical– Olfactory amygdala– Receives direct input form olfactory system, both the olfactory bulb and olfactory cortex

• Central Medial group– Main output of amygdaloid complex– Input from hippocampus, orbitofrontal, insula, anterior cingulate cortex as well as

basolateral group– Projects to hypothalamus, brainstem via stria terminalis and amygdaloventral fugal

pathway– Part of “central autonomic network”

http://www.driesen.com/amygdala_connections.htm

Price, Ann. NY Acad Sci., 985:50-58 (2003)

•Extended amygdala: Central medial group shares continuity and similarity with parts of substantia innominata and bed nucleus of the stria terminalis

Connections of the central medial group

cal.vet.upenn.edu/neuro/server/ slides/ns_075-BNST.jpg

The Hippocampus

• Greek: “Sea Monster”• Another terminology mess

– Allocortex/ archicortex– Hippocampal formation (after Amaral and Witter)

• Dentate gyrus• Hippocampus proper “Cornu ammonis”• Subicular complex

– Subiculum– Presubiculum– parasubiculum

• Entorhinal cortex

“C” shaped structure in medial temporal lobe

http://www.hallym.ac.kr/~de1610/nana/chp-12n.htm#IIFrom Digital Anatomist

Development

http://www.hallym.ac.kr/~de1610/nana/chp-12n.htm#II

From Digital Anatomist

From Digital Anatomist

Gross Anatomy

•Septal-temporal poles

•Fornix

•Fimbria, body, columns

Rodent

Human

Supracommissural hippocampus=supracallosal gyrus, indusium griseum

Connections•Afferents:

•Much of cortex is reciprocally connected to entorhinal cortex•Cholinergic and GABA input via septal nuclei•Amygdala•VTA, LC, Raphe

•Efferents•Via the fornix•Precommissural: septal nuclei•Post-commisural: mammillary bodies (to anterior thalamic nucleus via mammillothalamic tract)

Cytoarchitecture

Human

Rodent

•Two interlocking cell fields

•Dentate gyrus

•hippocampus

Hilus

CA1-CA3: pyramidal neurons

Dentate Gyrus: granule cells

www.deltagen.com/.../nervous/ cerebrum_hippo_10x.htm

sospsl

sr

ml

sl-m

•Stratum oriens•Stratum pyramidale•Stratum lucidum•Stratum radiatum•Stratum lacunosum-moleculare

•ml=molecular layer

Intrinsic connectionsCajal, 1901

http://www.angelfire.com/yt/yas709neuroscience/hippocampus.htm

Hypothalamus: General description

• Master regulator!!• Vital regulatory functions include: temperature, heart rate, blood

pressure, blood osmolarity, goal seeking behavior, emotional behavior, visceral nervous system, sexual activity, food & water intake

• homeostasis

• Below rostral thalamus (hypo =“under”/”beneath)• Forms floor and lower walls of third ventricle• Contains various classes of peptidergic neuroendocrine cells

which control endocrine function• Communicates with cortex via limbic system and also via direct

projections

Anatomy of Hypothalamus

science.tjc.edu/ images/brain/Index.htm

Anterior (supraoptic): preoptic, superchiasmatic, supraoptic, paraventricular

Middle (tuberal): dorsomedial, ventral medial nuclei, arcuate nucleus

Posterior (mammillary): mamllary body, posterior hypothalamic area, tubermammillary nucleus

Medial-Lateral Zones

Periventricular

Medial

Lateral

Cytoarchitecture

Macaque: brainmaps.org

Main Inputs to Hypothalamus

• receives info on external and internal conditions: – specific sensory info (e.g., direct retinal projection

to suprachiastmatic nucleus)– input from visceral senses (NTS: nucleus of the

solitary tract-taste)– contains many neurons that are sensitive to local

temperature, osmolarity, glucose, sodium– circulating hormones influence it via the

circumventricular organs• Brain regions near ventricles that lack a blood-brain

barrier, e.g., subfornical organ, OVLT, median eminence

Hypothalamus pathways

Afferent Pathway Projecting from

Median forebrain bundle Collaterals from other tracts

Fornix Hippocampus (to MB)

Stria terminalis amygdala

Efferent Pathway Projecting to

hypothalamicohypophyseal (from supraoptic nuclei)

Neurohypophysis (pituitary)

Mammillothalamic tract Anterior thalamic nucleus

Widespread projections to many brain regions, including the cerebral cortex, via histamine and hypocretin containing neurons in the tuberal region of the hypothalamus

“The medial forebrain bundle is one of the most famous hypothalamic fiber bundles, but also one of the most

incomprehensible”-Lennart Heimer

• Axons from olfactory related areas

• Monoaminergic axons• Ascending and

descending fibers similar to those found in the brain stem reticular formation

• Collaterals of other pathways

• Amygdalar fibersFrom braininfo.org

Peptidergic neuroendocrine cells: Magnocellular neurons

• “Large” neurons• Located in paraventricular and supraoptic

nuclei• Secrete oxytocin and vasopressin into

general circulation via posterior pituitary• Oxytocin uterine contraction & milk

ejection• Vasopressin vasoconstriction, water

resorption by the kidney

Magnocellular Secretory System

clem.mscd.edu/~raoa/ bio2320/endo1/sld003.htm

• “small” neurons• Located in medial basal region, arcuate and tuberal

nuclei, periventricular region, preoptic and paraventricular nuclei

• Secrete releasing and inhibiting hormones into portal vasculature via anterior pituitary

• Nobel prize awarded to Guillemin (Salk), Schally and Yalow in 1977 for their (independent) work in proving the hypothesis that the hypothalamus releases hormones that regulate the pituitary

Peptidergic neuroendocrine cells: Parvocellular neurons

Hypothalamic Portal System

clem.mscd.edu/~raoa/ bio2320/endo1/sld003.htm

Peripheral Influence of Hypothalamus

clem.mscd.edu/~raoa/ bio2320/endo1/sld003.htm

Hypocretin

From Thannickal et al., Neuron 27: 469, 2000

•Also known as “orexin”

•Peptide involved in arousal and feeding behavior

•Project to thalamus, cortex and brainstem regions associated with arousal, cardiovascular control, and autonomic functions

•Few thousand neurons

•Loss of hypocretin neurons implicated in human narcolepsy