Limbic System

The limbic system is a neuronal network that mediates emotion and motivation, while also playing a role in learning and memory. The extended neural network is vital to numerous basic psychological functions and plays an invaluable role in processing and responding to environmental stimuli.

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Structure and Function

The limbic system is a highly integrated system of structures with feedback mechanisms to appropriately balance the continuous stream of information that is received.


The limbic system is composed of several structures that produce subconscious responses to stimuli:

  • Olfactory pathways:
    • Input to the primary olfactory cortex via the uncus
    • Direct input to the amygdala: Olfactory emotions are associated with behavior.
    • Indirect input to the hippocampus: olfactory component of memory
    • Hippocampal to hypothalamic: mediates visceral responses to odors
    • Orbitofrontal cortex: olfactory perception of odors
  • Hippocampal formation:
    • Composed of the dentate gyrus, hippocampus proper, and entorhinal cortex
    • Location: floor of the inferior horn of the lateral ventricle
    • Inputs: dentate gyrus (input gate), amygdala, cingulate gyrus, and prefrontal cortex
    • Function: long-term memory and spatial navigation
  • Amygdala:
    • Located in the medial temporal lobe
    • Function: uses memory of stimuli to provide appropriate emotional responses upon reexposure to a given stimulus
  • Hypothalamus:
    • Communicates with the amygdala and prefrontal cortex
    • Controls the physiological aspects of emotion (perspiration, heart rate)
  • Septal nuclei of the limbic system: reciprocal connections from the olfactory bulb, hippocampus, and amygdala
  • Cingulate gyrus: modulation of the ANS and development of motivation
  • Mammillary bodies: mediate affective and sexual behavior


  • Mediates numerous functions including:
    • Emotion
    • Memory
    • Attention
    • Olfaction
    • ANS function
    • Feeding behavior
    • Mating behavior
  • The limbic system function can be remembered using the 5 “Fs”:
    • Feeding (hunger and satiety)
    • Forgetting (memory)
    • Fighting (emotional response)
    • Family (sexual reproduction and maternal instincts)
    • Fornicating (sexual arousal)

Papez Circuit

The Papez circuit is an interconnected network within the brain that is associated with many emotional processes. The Papez circuit involves the hippocampus, mammillary bodies, thalamus, and cingulate gyrus.

  • The Papez circuit is a modulator circuit involved in several functions, including:
    • Fear
    • Anxiety
    • Sadness
    • Happiness
    • Sexual pleasure
  • Consists of a number of limbic structures connected in a loop to modulate the above-mentioned behaviors:
    • Hippocampus → mammillary bodies → anterior nucleus of the thalamus → cingulate gyrus → hippocampus
    • The circuitry allows for memories to be stored based on the emotion produced by a stimulus.
Circuitry of the Papez loop

Circuitry of the Papez loop

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Clinical Relevance

  • Alzheimer disease: a chronic neurodegenerative disease due to the loss of neurons in the cerebral cortex and certain subcortical regions, resulting in gross atrophy and degenerative changes. The clinical features are memory impairment, loss of executive function and judgment, impaired cognitive function, and behavioral changes. Diagnosis is based on clinical examination, neuropsychiatric testing, and imaging. There is no cure, but the management of symptoms with medications may slow disease progression.
  • Olfaction: begins in a small area on the roof of the nasal cavity, which is covered with specialized mucosa. From this specialized area, the olfactory nerve transmits the sensory perception of smell via the olfactory pathway, which is composed of olfactory cells and olfactory bulb, tractus and striae olfactoriae, and the primary olfactory cortex and amygdala.
  • Sexual physiology: sexual physiology and development begin from early childhood, representing a complex process of events that leads to the final development of sexual orientation and behavior. Sexual behavior and interactions include several changes that are quite different between males and females. 
  • Wernicke encephalopathy and Korsakoff syndrome: occur due to a severe thiamine deficiency. It has an acute presentation and is reversible. This condition is most commonly seen in individuals with alcohol use disorder. The classic triad of symptoms is encephalopathy, oculomotor dysfunction, and gait ataxia. Korsakoff syndrome is a severe presentation of Wernicke encephalopathy and is attributed to chronic thiamine deficiency and alcohol use disorder. Korsakoff syndrome presents with personality changes, anterograde and retrograde amnesia, and confabulation.


  1. Seeley, W.W., Miller, B.L. (2018). Alzheimer’s disease. In Jameson, J.L., et al. (Eds.), Harrison’s Principles of Internal Medicine. 20th ed. Vol 2. pp. 3108-3114.
  2. Wolk, D.A., Dickerson, B.C. (2020). Clinical features and diagnosis of Alzheimer disease. UpToDate. Retrieved August 3, 2021, from
  3. Keene, C.D., Montine, T.J., Kuller, L.H. (2018). Epidemiology, pathology, and pathogenesis of Alzheimer disease. UpToDate. Retrieved August 3, 2021, from
  4. Forcier, M. (2020). Adolescent sexuality. UpToDate. Retrieved June 22, 2021, from

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