1. Limbic system Semmelweis University, Faculty of Medicine
2nd year 1st semester
Department of Human Morphology and Developmental Biology
Katalin Kocsis
21/10/2014

2. General view of the limbic brain
mammalian brain organized on the base of two major basic theories
1) Modularity theory
-specialised functions localized to different brain areas
2) Neuronal network theory
complex functions, features
- learning, memory, intelligence personality
- functional integration
- processing of information is in neuronal networks, scattered brain areas

3. Functions of the limbic system
Complex human functions:
-personality, behaviour, learning, memory, emotions
Basic functions
-reproduction, stress

4. Nomenclature Parolfactory area (subcallosal area)
-a small area of cortex on the medial surface of the frontal lobe,
immediately in front of and below the subcallosal (=paraterminal) gyrus
Gyrus subcallosus = gyrus paraterminalis
Septal nuclei
-in the septum pellucidum: only a few scattered neurons
- nuclei of „true septum” (septum verum) are ventral to the septum pellucidum
- extend into the subcallosal gyrus
Piriform cortex (olfactory cortex)= rhinecephalon = olfactory brain=nose brain
- olfactory bulb, tract, lat. olfactory stria, ant. perf. substance, ant. part parahippocampal gyrus,
uncus, amygdala (dorsomed)
-paleopallium, oldest part of hemisphere – projections to enthorinal cortex
Entorhinal cortex
-behind the ant. part of parahippocampal gyrus (piriform cortex)
-projections to hippocampal formation (archicortex)
Rhinal sulcus (16)
-minor sulcus in the parahippocampal gyrus on the ventral-medial margin of the anterior temporal lobe
-the rhinal sulcus continuous with the collateral sulcus along the lateral margin of parahippocampal gyrus
Isthmus of cingulate gyrus (9)
-connects the neocortical cingulate gyrus
to parahippocampal gyrus
paleocortex
archicortex
transitional
BrainInfo (2007),
Neuroscience Division, National Primate Research Center,
University of Washington,

5. Pierre Paul Broca (1878) – French neuroanatomist „Limbic lobe” – ring shaped cortical area on the medial surface of hemispheres: - parolfactory area (subcallosal area) - uncus - subcallosal gyrus (paraterminal gyrus) - parahippcampal gyrus - hippocampus - cingulate gyrus („limbic gyrus”) Smell is the main function of the limbic lobe
Pierre Paul Broca

6. -emotional feeling and expression
Papez presumed at first (1937): limbic lobe - functions related to the behaviour and emotions , emotions and motivated activity - localized in distinct brain structures
Papez proposed: -cingulate gyrus and hippocampus are connected with hypothalamus, anterior thalamic nuclei (limbic thalamus) through neuronal pathways:
Papez- circuit
-emotional feeling and expression
-interconnections constitute a harmonious mechanism
-cingulate gyrus is a receptive region for experiencing of emotion
Subcortical structures are connected to the limbic lobe:
Diencephalon
mamillary bodies
thalamic nuclei
medial and lateral habenular ncll.
James Papez
( )
American anatomist

8. Gyrus parahippocampalis
Gyrus uncinatus
Uncus
Limbus Giacomini
Gyrus intralimbicus
Gyrus parahippocampalis B

9. Components of limbic system
Cortical areas
gyrus cinguli
gyrus subcallosus
prefrontal cortical areas – anterior part of frontal lobe (rostral to motor areas)
piriform cortex –parahippocampal g. anterior part, including uncus, lat. olf. stria
entorhinal cortex – parahippocampalis g.
hippocampus
dentate gyrus
subiculum - pre/parasubiculum
parahippocampal gyrus
Subcortical limbic areas
Diencephalon habenula
mamillary body(hypothalamus)
anterior thalamic nuclei (limbic thalamus)
Telencephalon olfactory bulb
anterior olfactory nucleus
nucleus of the lateral olfactory tract
septum
nucleus tractus diagonalis
nucleus accumbens (ventral striatum)
amygdala
nucleus stria terminalis
Mesencephalon interpeduncular n., raphe dorsalis and medianus n.
ventral tegmental nucleus, centr. gray matter

10. Papez circle

11. Hippocampal formation: hippocampus, dentate gyrus, subiculum
Cortical afferents:
! -from: entorhinal area (fasciculus perforans)- glutamaterg◄amygdala, pr. olfactory c. 
- dentate gyrus str. moleculare – granule cells
-their mossy fibers activate the dendrites of CA3 pyramidal cells
through Schäfer collaterals activate CA1 pyramidal cells (trisynaptic excitatory pathw.)
-from contralateral hippocampusból
-from cingulate gyrus
Subcortical afferents:
-medial septal nuclei (cholinerg), caudal hypothalamus, amygdala, midbrain, thalamus
Cortical efferents - fornix:
-from CA1, CA2, CA3 areas: fibers extend to subiculum (transitional zone between the hippocampus and the bordering entorhinal cortex) and the entorhinal area
-from CA3: precommissural fornix to septum
-from CA1: postcommissuralfornix to mamillary body – anterior
thalamic nuclei – hypothalamus
CA3
CA2
Fasciculus
perforans
CA1
Functional aspects:
-memory processing functions
-learning
-stress
-vigilance

12. Hippocampal formation:hippocampus, gyrus dentatus, subiculum

13. Sulcus fimbriodentatus
Sulcus collateralis

14. Hippocampus and episodic memory
-epizodic memory (what–where-when) – memory of experienced events within spatiotemporal context
-„object-place memory task”– single specific event („object”) - particular occasion („place”)
-participants are instructed to remember of objects in a short time period, and asked to recall the arrangement of the objects after a delay period
„theta rhythm” (regular oscillation of the local field potential at frquencies of 3-12 Hz)
EEG theta oscillation increases during a successful recall
-theta oscillation is not a localized neuronal process, but distributes over the enthorhinal-hippocampal network
1)Θ osc. Generated in enthorinal cortex superficial II and III- layers
2)Extends into dentate gyrus, then through the mossy fibers
3)A Θ osc. into hippocampus CA3 zone
4)From CA3 Schafer collateráls into CA1 zóne
This network enables on-line real-time formation of memories of novel
experiences
Sato and Yamaguchi, 2007
-some hippocampal cells have preferred positions: „place cells” their preferred positions are called „place fields”
„in place field”
-a given position in the environmental space is represented precisely by the firing rates of „place cells”
-the population of active „place sejtek” continuously changes according to the running behavior in an environment

16. Prefrontal cortex - human
Complex functions:
-working memory, attention,
cognition, emotion
-executive control
-regulates behavioral inhibition
-jugdment, foresight
Prefrontal cortex - human
Dorsomedial prefrontal cortex
-extensive connections with sensorimotor and association neocortex (contemporary and past sensory experiences)
Orbitofrontal cortex
-strong connections with amygdaloid complex
-project heavily to subcortical limbic structures:
hypothalamus and septum
influences on behavioral and autonomic functions
Reciprocal relationship between dorsal and ventral prefrontal cortex
cognitive - emotional interactions

17. Amygdaloid complex Basolateral nuclei (younger)
Extraordinarily complex
Involved in many aspects of behavior but: there is no single high level function
Swanson and Petrowich:
„neither a structural nor a functional unit”
Amygdaloid complex
-implicated in emotional processing
-critically involved in mediating the stress on hippocampal memory processes – amygdalo-hippocampal interactions
Basolateral nuclei (younger)
-extensive reciprocal relations: sensory assotiation cortex (parietal, temporal), frontal lobe and
ventral striatum (putamen, and caudate n. ventral parts)
n. accumbens, Meynert’s n. basalis, dorsal thalamus
-projections from olfactory bulb, entorhinal cortex, cingulate gyrus, subcallosal area
Corticomedial nuclei (older)
-descending pathways to n. dorsalis n.vagi, brainstem cardiovascular centers,
locus coeruleus, n. raphe dorsalisventral tegmental nucleus
-peptidergic neurons(enkephalin, CRH, somatostatin, cholecystokinin)
-HYPOTHALAMUS – tractus amygdalo-hypothalamicus ventralis + stria terminalis - reciprocal
Many authors have attempted to divide this complex into clear functional units, largely without succes
corticomediális, basolaterális subnuclei

18. Nucleus accumbens (limbikus striatum)
N. accumbens functional aspects:
-responsible for motivated, goal-directed behaviors
-(compulsive drug seeking in cocaine addicts)
-interface between limbic and motor system
Normally descending projections from prefrontal cortex to n. accumbens, as well as other limbic regions, exert inhibitory control over reward-seeking behaviors

19. Changes of „award” system in heroin abuse
GABA (inhibitory) terminal
dopaminerg
terminal
, Heroin modifies the action of dopamine in the nucleus accumbens and the ventral tegemental area – (‘reward pathway’). Crossing the BBB, heroin is converted to morphine, which acts as a powerful agonist at the mu opioid receptors inhibiting the release of GABA from the nerve terminal, reducing the inhibitory effect of GABA on dopaminergic neurones. The increased release of dopamine results in sustained activation of the post-synaptic membrane. Continued activation of the dopaminergic reward pathway leads EUPHORIA.
Addiction uses same interneuronal connections as the learning and memory formation

20. limbic system scheme: afferentation
nucl. ant. thalami
limbic system scheme: afferentation

21. limbic system scheme: Papez circle
nucl. ant. thalami
limbic system scheme: Papez circle

22. limbic system scheme: efferentation
nucl. ant. thalami
limbic system scheme: efferentation

23. Papez circle
hippocampus

24. Pathology Wernicke-Korsakoff- encephalopathy
Before treatment
7 days thiamin treatment
Symptomes: apatia, confabulation, confusion, memory loss, inability to stand or walk without assistance
abnormal hyperintensity mamillary body and periaqueductal gray matter
Etiology: vitamin B1 deficiency

25. References