Limbic System and Hypothalamus

• The limbic system and hypothalamus are key brain structures.
• Class is Year 2, Semester 1.
• Lecturer is Dr. Vijayalakshmi S B from the Department of Anatomy.
• The lecture date is 3/11/2024.

Learning Outcomes

• Recognize the anatomical parts that make up the limbic system
• Describe the hypothalamus's position and functions
• Indicate the pituitary gland's position , relations, and function
• Explain how memory uses the limbic system
• Describe the effects of limbic component malfunction and their implications

Overview

• The hypothalamus deals with homeostasis based on internal inputs.
• The limbic system manages societal homeostasis, driven by external inputs at a foundational survival level.
• Associated neocortices relate to "societal homeostasis" based on external inputs at a higher level of association.

Hypothalamus Anatomy

• Optic chiasm and mammillary bodies are key structures.
• Crus cerebri and the interpeduncular fossa are relevant too.
• Cranial nerves CN III and CN IV are nearby

Hypothalamic Nucle

• Hypothalamic nuclei includes: thalamus, fornix, hypothalamic sulcus, anterior commissure, paraventricular, posterior, dorsomedial, supraoptic, ventromedial, tuberal, mammillary, optic chiasm, infundibulum (pituitary stalk), and hypophysis (pituitary gland).
• Mamillothalamic tract, the dorsal longitudinal fasciculus, and other descending pathways are other key structures in the region.

Hypothalamus

• Integrates signals from internal organs and fluid-filled cavities.
• Maintains homeostasis via input and output systems.
• It forms part of the diencephalon.
• The pituitary gland is attached to it.
• Inputs arrive via blood (hormonal) and the brainstem (neural).
• Output is mediated via the pituitary gland (hormonal and neural) and the limbic system (neural).

Hypothalamus Functions

• Manages fluid and electrolytes
• Regulates food ingestion
• Regulates body temperature
• Deals with reproduction
• Coordinates immune responses
• Manages circadian rhythms
• Controls emotional responses, acting as a brain center for autonomic nervous system regulation

Hypothalamic Inputs

• Blood is sampled in the hypothalamus.
• Physical factors: temperature and osmolality are monitored.
• Chemical factors such as glucose and acid-base balance are also sampled.
• Hormones such as growth, development, and action hormones (fight/flight, sex hormones) are monitored.
• Neural inputs from the nucleus solitarius in the medulla include baroreceptors and chemoreceptors.
• Reticular formation in the medulla and pons gives information pertaining to the state of neural arousal.
• Limbic and thalamic inputs are also important.

Hypothalamic Outputs

• Direct hormone production includes vasopressin (ADH) and oxytocin.
• Pituitary gland control via the hypophyseal portal system connects the two, and involves releasing and anti-releasing factors.
• Autonomic nervous system regulation includes thermoregulation, fight or flight response, and appetite/thirst.
• It influences the limbic system by initiating appropriate (instinctive) motor behavioral responses and affecting the limbic part of the basal ganglia.

Hypothalamic Hormonal Outputs

• Supraoptic nucleus hormone outputs include the vasopressin (ADH).
• Supraoptic nucleus is activated by osmoreceptors when osmolality increases.
• Paraventricular nucleus produces oxytocin, causing mammary gland milk production and uterine muscle contraction.

Anterior Pituitary Hormonal Outputs

• Median eminence is key.
• It outputs releasing and anti releasing factors.

Hypothalamic/Pituitary Tumors

• Endocrine problems arise due to over or under-production of circulating hormones.
• Excess prolactin causes infertility.
• Excess cortisol results in Cushing’s syndrome (appearance, osteoporosis, weakness, diabetes).
• Hypoadrenalism/adrenal insufficiency leads to Addison’s disease (hyperpigmentation, low BP, tachycardia).
• Tumors can cause growth disorders like dwarfism, gigantism, acromegaly.
• Sexual function abnormalities can occur.
• Body water control issues can arise such as diabetes insipidus.
• Eating disorders can manifest, including obesity and bulimia.
• Pressure effects occur when compression of the posteromedial aspect of the optic chiasm results in bitemporal visual field loss.

Limbic System

• The limbic system forms an arched border area between the neocortex and diencephalic structures, including the thalamus and hypothalamus.
• Its components are the cingulate gyrus, hippocampal formation, fornix, mammillary bodies, septal nuclei, N. accumbens, and amygdala.

Anatomical Structure

• Limbic structures include the cingulate gyrus, parahippocampal gyrus, hippocampal formation, amygdaloid nucleus, mammillary bodies, and anterior thalamic nucleus.
• Connecting pathways involve structures like the alveus, fimbria, fornix, mammillothalamic tract, and stria terminalis.

Limbic System Relationship

• Limbic structures are associated with the cerebral cortex.
• Relationship to the hypothalamus and spinal cord
• Key links to the reticular formation

Major Functions

• The limbic system influences emotional behavior
• Converts recent memories into long-term memory
• Links effective homeostatic responses to environmental stimuli

Limbic System and Memory

• The anterior nucleus of the thalamus and cingulate gyrus are involved in memory.
• Nucleus accumbens and mammillary body are also involved.
• The hippocampus makes new memories.
• Entorhinal cortex decides on how memories are made.
• The medial dorsal nucleus contributes to memory.
• The dentate gyrus contributes to episodic memory formation.

Papez Circuit

• Papez curcuit consists of the cingulate gyrus, internal capsule, anterior thalamic nucleus, fornix, mammillothalamic tract, lateral and medial mammillary nuclei, subiculum, alvear and perforant pathways, parahippocampal gyrus and entorhinal cortex.

Hippocampal Formation

• The hippocampal formation consists of the hippocampus, dentate gyrus, and part of the parahippocampal gyrus.
• Receives ipsilateral afferents from the inferior temporal cortex via entorhinal cortex
• Receives contralateral afferents from hippocampus and entorhinal cortex via fornix, and the hippocampal commissure
• Has an efferent pathway through the Fornix

Hippocampus Location

• The hippocampus is inferomedial to the floor of the inferior horn of the lateral ventricle; it is on the medial surface of the temporal lobe.
• The hippocampus is also known as a "seahorse."

Clinical Aspects - Alzheimer’s Disease

• Hippocampal degeneration prevents the formation of new memories in people with Alzheimer’s disease.
• A key symptom is anterograde amnesia affecting recent events.
• There is loss of episodic and new autobiographical memory.

Other Cortical Degenerations

• Fronto-temporal dementia involves prefrontal cortex degeneration, leading to inappropriate behavior and deficits in attention and motivation.
• Semantic dementia involves atrophy of middle and inferior temporal neocortex; patients lose meaning of words and perception while autobiographical memories are preserved.

Fornix

• Main efferent from hippocampus made of fimbria.
• Partial decussation occurs at the crus.
• It splits into two bundles; anterior and posterior
• The posterior supplies mammillary bodies with short-term memories and smell from nasal fibers.
• The anterior supplies septal nuclei with N. accumbens

Nucleus Accumbens and Septal Area

• Stimulation - sense of well-being due to dopaminergic activity.
• Cocaine inhibits the reuptake of dopamine and floods the medial forebrain.
• Amphetamines stimulate dopamine release.
• Connection to basal nuclei for motor expression of emotion
• Stimulation - sensation like orgasm
• Destruction - rage

Amygdala

• Location - At the tip of the tail of the caudate nucleus and inferior horn of the lateral ventricle (at the anterior pole of the temporal lobe)

• Stimulation causes intense emotions, e.g., fear, aggression -Fear - important for survival -Overactivity – rage -Role in phobias -Bilateral ablation – complete calmness, hypersexuality.

Memory and Learning

• Reward centers in the medial forebrain bundle (septal nuclei, nucleus accumbens, olfactory regions and brainstem)
• Punishment centers are the Periaqueductal grey, thalamus, amygdala, and hippocampus
• Reward/Punishment – learning
• Repetition – Habituation

Clinical Aspects of Wernicke-Korsakoff Syndrome

• Causes amnesia (memory loss) of both anterograde and retrograde memory
• Deficiency typically associated with the toxic effects of alcohol or from a Vitamin B1 (thiamine) deficiency.
• Neurons in the hippocampal formation and other parts of the Papez circuit are particularly affected
• Korsakoff's syndrome is often, but not always, preceded by an episode of Wernicke encephalopathy, which is an acute brain reaction to a severe lack of thiamine.
• Memory loss and inability to form new memories

Wernicke Encephalopathy

• Is linked to alcoholism and severe thiamine (B1) deficiency; "Dry beriberi" with peripheral neuropathy
• Shows + microhemorrhages in tegmentum, cerebellar vermis and mammillary bodies known as the clinical triad:
• Ocular palsy nystagmus (Cr. N 6)
• Ataxia (cerebellum)
• Confusion (mammillary body)

Clinical Aspects/Kluver-Bucy Syndrome

• Klüver-Bucy Syndrome manifests following bilateral anterior temporal lobectomy, including the amygdala.
• Symptoms include no fear, excessive tameness, flat affect, agnosia, oral exploration, indiscriminate dietary behavior, and autoeroticism, plus anterograde amnesia if hippocampi are involved.

Amydala Rage

• Electrical Stimulation of Amygdala = Targeted Rage
• Amygdala-Rage is seen in Temporal Lobe Epilepsy
• Rage lasts long after stimulation