1. Limbic System
Dr. G.R. Leichnetz

2. What is the Limbic System?
The limbic system is a network of structures involved in the incorporation of an emotional component into the broad range of human behaviors.
The amygdala attaches an “emotional tag” to ongoing sensory experience, and may lead to responses of fear or anxiety where the stimuli are threatening.
The hippocampus depends on the emotional significance of ongoing and remembered sensory experience to determine what information is essential for memory processing.
The hypothalamus receives major limbic input from the amygdala such that emotion affects autonomic and endocrine functions.
The basal forebrain is a nexus between the limbic system and basal ganglia where emotion affects motivation (eg. reward) and movement.
The prefrontal cortex receives limbic input that affects mood & personality, and working memory.

3. First defined by Broca in the late 19th century, the “limbic lobe” is an arcuate convolution of cortex on the medial aspect of the hemisphere, consisting of subcallosal gyrus, cingulate gyrus, parahippocampal gyrus (and underlying hippocampal formation).

4. The term “limbic system” includes the limbic lobe cortex and other subcortical structures which are involved in emotion, including the hippocampus, amygdala, basal forebrain, and hypothalamus.
This figure from Dr. Solomon Snyder, Johns Hopkins U., illustrates structures with high opiate receptors.

5. Limbic System Core: Septo-Mesencephalic Limbic Continuum Contemporary definitions of what is considered “limbic” includes those structures that have connections with this limbic core from the septum, through the hypothalamus, to the “midbrain limbic area” (raphe).
SEPTUM
MIDBRAIN LIMBIC AREA (RAPHE)
From: Niewenhuys, The Human Nervous System

6. HIPPOCAMPUS

7. Its principal efferent fiber system is the fornix.
Olfactory tract
The parahippocampal gyrus is located in the ventromedial temporal lobe.
The hippocampal formation lies deep to the cortex of the parahippocampal gyrus (removed).
Its principal efferent fiber system is the fornix.
Hypothalamus
Entorhinal cortex
Amygdala
Uncus MB
Hippocampal formation
Fornix

8. Hippocampal Formation
The hippocampal formation consists of the hippocampus proper, dentate gyrus, and subiculum. The subiculum is a transitional cortex between the six-layered entorhinal cortex and the trilaminar cortex of the hippocampus.
Hippocampus proper
Dentate gyrus
Entorhinal Cortex
subiculum

9. Hippocampal Formation
Fimbria of fornix
CA3
Hippocampus proper
Dentate gyrus
Entorhinal cortex
CA1
Subiculum
The hippocampus proper consists of CA1-CA3 subfields. The dentate gyrus consists of CA4 plus the “dentate fascia,” ie. molecular and granular layers of the dentate gyrus.

10. The principal source of direct afferents to the hippocampus is the entorhinal cortex which covers the surface of the rostral parahippocampal gyrus; called the “gateway to the hippocampus” because it is a major pre-hippocampal relay station.
Entorhinal cortex (principal source of direct afferents to hippocampus)
Parahippocampal gyrus
Collateral sulcus (rhinal sulcus in mammals)

11. The entorhinal cortex receives major multimodal input (somatosensory, visual, auditory) from associational cortex, and relays that information into the hippocampus for memory processing.
Temporal assoc. cortex
Prefrontal assoc. cortex
Parieto-occipital assoc. cortex
Entorhinal Afferents

12. The entorhinal input into the hippocampus follows two paths: perforant path and alvear path
The entorhinal inputs into the hippocampus are precisely organized Perforant path primarily to dentate gyrus Alvear path to hippocampus proper.
From: Carpenter, Human Neuroanatomy

13. Intrinsic Hippocampal Connections:
Importance: Intra-hippocampal processing for memory processing
From: Kiernan and Barr
Hippocampal efferents leave thru fimbia of fornix
Dentate granule cells
Entorhinal Cortex
Entorhinal afferents from associational cortex

14. The fornix is the principal efferent tract of the hippocampus.
Body
Columns
Postcommissural
Crus
Fimbria
Hippocampal commissure

15. The precommissural fornix terminates in the septum/basal forebrain region. The postcommissural fornix projects to hypothalamus, mammillary body, and brainstem reticular formation.
From: Noback & Demarest, The Human Nervous System

16. The fornix is the first segment of the classic “Papez circuit
The fornix is the first segment of the classic “Papez circuit.” It projects to the mammillary body, followed by the mammillothalamic tract to anterior nucleus of thalamus, cingulate gyrus, and cingulum bundle back to the hippocampus.
Cingulate gyrus
Papez thought that this circuit was a “reverberating circuit for emotion.”
cingulum
Ant. Nuc.
fornix
MTT
MTT
Mamm. Body
ANT
Hippoc. MB

17. Bilateral lesions of the hippocampus produce anterograde amnesia, inability to form new memories Past memories are largely intact.
The CA1 subfield (Sommer’s Sector) is vulnerable to vascular injury due to hemorrhage of small caliber anterior choroidal arteries.

18. Kornhuber postulated that Papez circuit is a “limbic selection unit” in which essential information is selected for incorporation into memory.
PAPEZ CIRCUIT

19. Wernicke’s encephalopathy (from a vitamin B1 thiamin deficiency) produces focal vascular hemorrhages in structures associated with Papez circuit (eg. mammillary bodies, anterior nucleus of thalamus) and results in Korsakoff’s syndrome with amnesia.

20. AMYGDALA

21. The amygdala is located in the ventromedial temporal lobe (rostral to the hippocampus) within the rostral parahippocampal gyrus. C
The amygdala consists of numerous subnuclei, thus often referred to as the “amygdaloid complex”.
MEDIAL
LATERAL

22. The medial group of subnuclei receive direct olfactory input.
Amygdaloid Complex
The medial group of subnuclei receive direct olfactory input.
The lateral group receives its input primarily from adjacent temporal cortex, and other regions of associational cortex that relay multi-modal sensory information.
The central nucleus in the origin of the amygdaloid efferents to brainstem autonomic nuclei. C
MEDIAL
LATERAL

23. AMYGDALOID AFFERENTS
1. Multimodal Sensory Inputs- via relay in adjacent temporal cortex, informs the amygdala about ongoing sensory experience
2. Direct Olfactory Input- from olfactory bulb
Normal sensory “percepts” interact with the amygdala to be “tagged” with an appropriate emotional or motivational significance.

24. The amygdaloid complex receives multimodal sensory input (via relay in adjacent temporal cortex) and adds an “emotional tag” to sensory experience.
Multimodal sensory input

25. AMYGDALOID EFFERENTS Cortical Efferents-
The amygdala has feedback projections to somatosensory, visual, and auditory associational cortex to bring “emotional salience” to ongoing sensory experience (attention).
From: Purves et al

26. AMYGDALOID EFFERENTS
Subcortical Efferents- via stria terminalis & ansa peduncularis to:
Hypothalamus- feeding/appetite, reproductive behavior, endocrine releasing factors
Mediodorsal nucleus of thalamus- relay to prefrontal cortex (for emotional effects on mood personality, social behavior, working memory)
Basal forebrain (nuc. accumbens)- addiction, pleasure/ reward
Brainstem autonomic nuclei- effects on autonomics (cardiac, respiratory)

27. Amygdaloid efferents follow two paths:
Amygdaloid efferents follow two paths: stria terminalis and ansa peduncularis.
From:Noback & Demarest, The Human Nervous System

28. Ansa Peduncularis: the ventral amygdalofugal pathway carries projections to basal forebrain (nuc. accumbens), MD nuc. thalamus, hypothalamus, and brainstem autonomic nuclei.
To MD
To NA
Hypothalamus
Amygdala
To brainstem autonomic nuclei

29. Ansa Peduncularis
The amygdala projects to the hypothalamus, mediodorsal nucleus of thalamus, basal forebrain (n. accumbens), and brainstem autonomic nuclei adding emotional component to behaviors.
Stria terminalis MD
Hypothalamus
Ansa Peduncularis
Brainstem autonomic nuclei
From: Niewenhuys, The Human Nervous System

31. AMYGDALOID LESION
Temporal lobe lesions which involve the amygdala result in Kluver-Bucy Syndrome, producing lack of emotion, fear; inability to discriminate between food and non-food objects, hypersexuality.
The amygdala plays a central role in evaluating environmental stimuli in selection of food, or mate, or avoidance of dangerous situations or substances.
Years ago, amygdalectomies were performed on criminals to reduce their aggressive behavior

32. SEPTUM/BASAL FOREBRAIN

33. The precommissural septum/ basal forebrain is a major nexus in the limbic system.
Septum pellucidum
Fornix AC
Precommissural septum
Hypothalamus MB
Basal forebrain

34. The precommissural septum is contiguous with the basal forebrain
The precommissural septum is contiguous with the basal forebrain. The septum/basal forebrain region contains the nucleus accumbens and numerous cholinergic nuclei (Ch1-Ch4)
Caudate
Putamen S
N. Acc.
Ch1-Ch3
Ch4
Basal forebrain
From: Niewenhuys, The Human Nervous System

35. The nucleus accumbens is the largest nucleus of the septum/basal forebrain, and is the “center for addiction.” It receives the DA mesolimbic “reward system” from the ventral tegmental area of the midbrain. C IC S P NA
Basal forebrain
Sometimes referred to as the “ventral striatum”

36. The mesolimbic and mesocortical tracts, which originate from the VTA (A10) traverse the medial forebrain bundle in the lateral hypothalamus to reach the nucleus accumbens and prefrontal cortex.
PFC NA
VTA
Mesocortical
Mesolimbic Reward System
Traverse the medial forebrain bundle
From: Niewenhuys, The Human Nervous System

37. The nucleus accumbens has been called a “center for addiction
The nucleus accumbens has been called a “center for addiction.” It receives the major dopaminergic “reward system” (mesolimbic) projections from the ventral tegmental area of the midbrain. Its neurons have receptors to most chemical substances of abuse (opioids, nicotine).
When accumbens is stimulated it is pleasurable. Amygdaloid projections to accumbens bring “emotional” component to addiction.
Functional MRI studies show that the amygdala and nucleus accumbens are activated even in the absence of cocaine if the subject “imagines” the emotional high.

38. The medial forebrain bundle is a fiber system that traverses the lateral hypothalamus and carries both afferent and efferent fibers to and from the nuclei in the septum/basal forebrain.
Medial forebrain bundle
From: Niewenhuys, The Human Nervous System

39. Ascending NE projections from the locus ceruleus (A6) and cell groups A5, A7 traverse the MFB
LC (A6)
CELL GROUPS A5, A7
The medial forebrain bundle is a conduit for ascending neurotransmitter- specific fiber systems.
MFB
MIDBRAIN RAPHE (B7,B8)
Ascending serotonergic projections from the midbrain raphe (B7, B8) traverse the MFB
From: Niewenhuys, The Human Nervous System

40. SEPTUM/BASAL FOREBRAIN
Afferents
Medial Forebrain Bundle (DA, NE, 5-HT) Fornix (from hippocampus) Stria terminalis, ansa peduncularis (from amygdala)
Efferents
Medial Forebrain Bundle (ACh) (to hypothalamus, and brainstem Reciprocal thru fornix (to hippocampus) and stria terminalis, ansa peduncularis (to amygdala)
ACh projections (Ch4)- to cerebral cortex

41. The nucleus basalis of Meynert (Ch4), located in the basal forebrain, is the principal source of cholinergic innervation of the cerebral cortex. This nucleus shows a profound loss of neurons in Alzheimer’s disease.

42. The medial forebrain bundle carries descending cholinergic projections from nuclei in the septum/basal forebrain (Ch1-Ch3) to the hypothalamus and brainstem reticular formation.
Medial forebrain bundle
Ch1-Ch3)
From: Niewenhuys, The Human Nervous System

43. PREFRONTAL CORTEX

44. The prefrontal cortex is the “neocortical representative of the limbic system.”
It receives major limbic input from the amygdala relayed via the MD nucleus of the thalamus, affecting its role in mood and personality.

45. Prefrontal Cortex
The prefrontal cortex receives a major input from the mediodorsal (MD) nucleus of the thalamus, which conveys limbic influence from the amygdala.
Mediodorsal nucleus

46. Phineas Gage
Using the archived skull of Phineas Gage, investigators reconstructed the trajectory of the iron tamping rod thru his prefrontal cortex.
“…survived a different man… profound change in personality…no impairment of movement or speech…had become irreverant and capricious. His respect for social conventions had vanished. His abundant profanity offended those around him… he had taken leave of his sense of responsibility…”