The Limbic System PDF

**Case Study: Patient HM** Patient H.M. (Henry Molaison) underwent surgery in 1953 to treat severe epilepsy, which involved the removal of his medial temporal lobes, including the hippocampus. While the surgery reduced his seizures, it caused profound memory impairments. H.M. developed severe anter...

**Case Study: Patient HM** Patient H.M. (Henry Molaison) underwent surgery in 1953 to treat severe epilepsy, which involved the removal of his medial temporal lobes, including the hippocampus. While the surgery reduced his seizures, it caused profound memory impairments. H.M. developed severe anterograde amnesia, losing the ability to form new explicit (declarative) memories, and partial retrograde amnesia, affecting memories from the years before the surgery. However, his implicit memory (e.g., motor skill learning) remained intact. H.M.'s case revealed the critical role of the hippocampus in forming new long-term memories and consolidating short-term memories into lasting ones. It also demonstrated that memory is not a single process but consists of distinct systems, such as explicit and implicit memory, mediated by different brain structures. His contributions transformed our understanding of memory and the brain, making his case one of the most important in neuroscience history. **The Circuit of Papez:** The **Papez circuit** was proposed by James Papez in 1937 as a neural circuit for the control of emotion. The original components of the circus are (1) **Hypothalamus** (mammillary bodies), (2) **Anterior nucleus of thalamus**, (3) **Cingulate cortex**, (4) **Hippocampus**. Paul MacLean expanded upon Papez's original concept of the limbic system in the 1940s and 1950s, redefining the **limbic lobe** as part of a broader system that integrates emotion, behaviour, and memory. The limbic structures: (1) **Cingulate cortex**, (2) **Parahippocampal gyrus**, (3) **The amygdala**, (4) **The hippocampus**, (5) **The hypothalamus**. **Olfaction:** Sense Of Smell. One of the **5 traditional senses**: Smell (olfaction), sight (vision, ophthalmoception), hearing (audioception), taste (gustatory, gustaoception), and touch (tactioception) **Other senses**: Temperature (thermoception), Kinesthetic sense (proprioception), Pain (nociception), Balance (equilibrioception), Various internal stimuli (e.g. chemoreceptors). **The Five Traditional Senses and Their Associated Cranial Nerves:** All associated with specific Cranial Nerves. **Senses:** **Cranial Nerve:** ------------- --------------------------------- Smell Olfactory (I) Sight Optic (II) Hearing Vestibulocochlear (VIII) Taste VII - facial, IX glsph, X Vagus Touch Trigeminal (V)  **Olfactory signal initiation and transmission:** **Olfactory Receptor Neurons (ORNs):** Are bipolar cells in the olfactory epithelium of the nasal cavity. Cilia contain odorant receptors that detect specific odours. Binding of odorants triggers action potentials. **Transmission to the Olfactory Bulb:** Axons of ORNs project to glomeruli in the olfactory bulb. Glomeruli are synaptic sites where ORNs connect with mitral and tufted cells. **Processing and Higher Brain Transmission:** Mitral/tufted cells relay signals to the olfactory cortex and limbic system (amygdala and hippocampus) for emotional and memory processing. **Organisation of the glomerular layer:** - **Olfactory Receptor Neurons (ORNs):** Neurons with the same receptor type project to the same glomerulus, forming a map for odour processing. - **Mitral and Tufted Cells (M/T):** These cells synapse with ORNs in the glomerulus and transmit signals to higher brain areas. - **Periglomerular Cells (PG):** Inhibitory interneurons that provide lateral inhibition within and between glomeruli to refine signal processing. - **Granule Cells (GR):** Inhibitory interneurons that mediate lateral inhibition between mitral/tufted cells to modulate signal transmission. - **Neurotransmitters:** Inhibitory cells use GABA, dopamine, and glycine to regulate olfactory signal processing. **Connections of the Olfactory Neurons in Mammals:** - **Olfactory Neuron Axons:** Olfactory neurons send their axons to the olfactory bulb for further processing of odour signals. - **Olfactory Bulb Structure:** The olfactory bulb is composed of multiple layers, with the glomerular layer being the peripheral layer where axons from the olfactory neurons terminate. - **Convergence on Glomeruli:** Many axons from olfactory neurons converge onto a single glomerulus. Neurons with the same odorant receptor (OR) type send their axons to the same glomerulus, while neurons with different ORs project to different glomeruli. - **Glomerular Activation:** In rats, around 15 million olfactory neurons converge onto \~1500 glomeruli (\~10,000:1 ratio). This organization means that the activation of specific odour receptors leads to the activation of different glomeruli. - **Encoding Smells:** The combination of activated glomeruli forms a unique pattern that encodes the specific smell being detected. Each odour activates a distinct combination of glomeruli, which is interpreted by the brain as a specific odour. **Terminal areas of the main olfactory pathway (human):**  The **olfactory pathway** begins in the **primary olfactory cortex** (POC) located in the **uncus** and **passes** through various brain regions, including the **entorhinal cortex**, **olfactory tubercle**, **thalamus**, and **orbitofrontal cortex**. It **connects** to areas involved in memory (**hippocampus**), emotion (**amygdala**), and autonomic regulation (**hypothalamus**), with communication between the hemispheres through the **anterior commissure**. This intricate pathway **links smell perception** to **emotional, memory, and physiological responses**. **Olfaction in Humans vs Animals:** **Olfactory Ability in Humans:** **Odour Detection:** Humans can sense over 10,000 different odours. **Sensitivity:** The detection threshold for odours can be as low as parts per million (ppm) or even parts per billion (ppb). **Role**: In humans, smell is primarily an aesthetic sense, contributing to experiences like taste, memory, and emotional responses, but it is not as central to survival. **Olfactory Ability in Animals:** **Enhanced Sensitivity:** In many animals, olfaction is much more advanced. For example, scent-tracking dogs have an olfactory sensitivity that is about 10 million times more sensitive than in humans. **Survival Role**: For animals, smell plays a vital role in survival, directing them to: **Food**: Helping locate sources of nourishment. **Potential Mates:** Aiding in reproduction through scent detection. **Avoiding Danger**: Allowing animals to detect predators or hazards through scent cues. **Amygdala:** 4 main subdivisions: **The Basolateral Amygdala** (BLA) processes sensory and emotional learning. **The Olfactory Amygdala** (CoA) links smells with emotions. **The Centromedial Amygdala** (Ce, Me) mediates emotional responses and autonomic reactions. **The Extended Amygdala** plays a role in emotion regulation, stress, and anxiety. **Basolateral amygdala**. Basolateral amygdala receives highly processed information from modality specific cortical association areas and through reciprocal connections affects processing of sensory information. It can also affect cortical processing via reciprocal thalamoamygdaloid (viscerosensory and auditory relay nuclei) and striatal connections.\ **Olfactory (Cortical) amygdala** receives input from both olfactory bulb and olfactory cortex and is involved in processing of olfactory information. It\ projects to centromedial amygdala and hypothalamus.\ **Centromedial amygdala and Extended amygdala** receive primary inputs from hippocampal formation, insula and orbitofrontal cortex (also cerebral cortex) and other parts of amygdala. They project to many regions in hypothalamus and brain stem. They support and affect autonomic, endocrine and somatomotor aspects of emotional and eating, drinking, sexual behaviour. **Hippocampus:**  1. **Fornix** - fibre connection between hippocampus and the hypothalamus. 2. **Amygdalo-hypothalamic fibres** (not shown here) pass from amygdala complex to the hypothalamus through the stria terminalis. **The hippocampus is subdivided into several regions, one of the most important being the Cornu Ammonis (CA) regions, which are traditionally numbered from CA1 to CA4.** The hippocampal **tri-synaptic circuit** is crucial for memory formation, consolidation, and retrieval, particularly for spatial and episodic memories. It involves **three key synapses** that connect different regions of the hippocampus, allowing for efficient processing of sensory and emotional information. 1. **Entorhinal Cortex → Dentate Gyrus** (via the perforant pathway): The entorhinal cortex activates granule cells in the dentate gyrus, important for **pattern separation** (distinguishing similar experiences). 2. **Dentate Gyrus → CA3** (via mossy fibres): The granule cells send axons (mossy fibres) to **CA3 pyramidal cells**, aiding in **pattern completion** (retrieving memories from partial cues). 3. **CA3 → CA1** (via Schaffer collaterals): CA3 pyramidal cells transmit information to **CA1** for **final processing** and output to other brain regions, contributing to memory storage and retrieval. **Hypothalamus:** The hypothalamus is a **primary regulator** of **autonomic** and **endocrine functions**.\ It **controls** or modifies a variety of **homeostatic processes** that include respiration, circulation, food-water intake, digestion, metabolism, and body temperature.\ A **properly functioning hypothalamus is crucial** for the harmonious growth of the body, for differentiation of sexual characteristics, and for sexual and reproductive activities.  **Stress Reaction: Hypothalamic--Pituitary--Adrenal (HPA) Axis:** The **HPA axis** is the body\'s central stress response system, where the hypothalamus releases CRH, prompting the pituitary to secrete ACTH, which stimulates the adrenal glands to release cortisol for energy and stress regulation. The hypothalamus also governs critical survival behaviours---**fighting, fleeing, feeding**, and **mating**---by integrating nervous and hormonal signals to maintain homeostasis and adaptive responses. **MRI of Hypothalamus:** The **mammillary nucleus**, part of the hypothalamus, plays a key role in memory and is a crucial component of the Papez circuit. Its main connections include **Afferent and Efferent connections**. **Afferent Connections to the Hypothalamus:** 1. **Somatic and Visceral Afferents**: General somatic sensations, as well as gustatory and visceral inputs, reach the hypothalamus through collateral branches of the lemniscal afferent fibers, the tractus solitarius, and the reticular formation. 2. **Visual Afferents**: Signals from the optic chiasma project to the suprachiasmatic nucleus, enabling the hypothalamus to regulate circadian rhythms. 3. **Olfactory Afferents**: Olfactory signals are transmitted to the hypothalamus via the medial forebrain bundle. 4. **Auditory Afferents**: Though specific auditory pathways to the hypothalamus have not been identified, auditory stimuli can modulate hypothalamic activity, suggesting indirect connections. 5. **Corticohypothalamic Fibers**: These originate in the frontal lobe of the cerebral cortex and project directly to the hypothalamus, integrating higher-order cortical inputs. 6. **Hippocampo-Hypothalamic Fibers**: Axons from the hippocampus travel through the fornix to the mammillary body, linking memory-related circuits with hypothalamic functions. The hypothalamus is often viewed as the primary output of the limbic system. 7. **Amygdalo-Hypothalamic Fibers**: The amygdala communicates with the hypothalamus through the stria terminalis, passing inferior to the lentiform nucleus to relay emotional and autonomic signals. 8. **Thalamo-Hypothalamic Fibers**: These arise from the dorsomedial and midline nuclei of the thalamus, providing reciprocal communication between the thalamus and hypothalamus. 9. **Tegmento-Hypothalamic Fibers**: Inputs from the midbrain tegmentum project to the hypothalamus, linking brainstem autonomic centres. **Efferent Connections of the Hypothalamus:** 1. **Descending Fibers to Brainstem and Spinal Cord:** These fibres influence the autonomic nervous system (ANS) by descending through the reticular formation. The hypothalamus connects to parasympathetic nuclei of cranial nerves: oculomotor (III), facial (VII), glossopharyngeal (IX), and Vagus (X). Reticulospinal fibres link the hypothalamus with: - Sympathetic neurons in the lateral grey horns of the spinal cord (T1--L2). - Parasympathetic outflow at the sacral spinal segments (S2--S4). 2. **Mammillothalamic Tract:** Originates in the mammillary body and terminates in the anterior thalamic nucleus. This pathway relays to the cingulate gyrus, integrating memory and emotional processing. 3. **Mammillotegmental Tract:** Arises from the mammillary body and projects to the reticular formation in the midbrain tegmentum, influencing autonomic and arousal functions. 4. **Connections to the Limbic System:** The hypothalamus maintains extensive connections with the limbic system, facilitating the regulation of emotions, behaviour, and homeostatic processes. The hypothalamus plays a central role in the **circadian regulation of melatonin production** through its control of the suprachiasmatic nucleus (SCN), which is located within the hypothalamus and serves as the body\'s master clock. **Hypothalamic Functions and Effects of Lesions:** 1. **Temperature Regulation: Anterior Hypothalamus Lesion:** Causes hyperthermia (inability to dissipate heat effectively). Posterior Hypothalamus Lesion: Causes hypothermia (impaired ability to generate heat). 2. **Food Intake: Ventromedial Nucleus Lesion:** Leads to hyperphagia (excessive eating), as this area normally suppresses hunger. Lateral Hypothalamus Lesion: Results in hypophagia (reduced eating), as this region stimulates hunger. 3. **Sleep-Wake Cycle: Anterior Hypothalamus Lesion:** Causes insomnia, disrupting the ability to initiate and maintain sleep. Posterior Hypothalamus Lesion: Leads to hypersomnia, resulting in excessive sleepiness. 4. **Emotions: Ventromedial Nucleus Lesion:** Produces rage and aggressive behaviour, as this area helps regulate emotional responses. 5. **Water Balance: Anterior Hypothalamus Lesion:** Causes diabetes insipidus, characterized by excessive thirst and urination due to impaired control of water balance.