Limbic System PDF

# The Limbic System ## Learning Objectives: - Define the limbic lobe, Papez circuit, limbic system, and name some of the limbic structures, and their function. - Describe the anatomy of the olfactory system, its circuitry and relationship to the limbic structures. - Describe the subdivisions of am...

# The Limbic System ## Learning Objectives: - Define the limbic lobe, Papez circuit, limbic system, and name some of the limbic structures, and their function. - Describe the anatomy of the olfactory system, its circuitry and relationship to the limbic structures. - Describe the subdivisions of amygdala and its connections. - Describe the components of the trisynaptic circuit of the hippocampus and its connections. Name some of its functional roles. - Name the three regional subdivisions of the hypothalamus and its function. - Describe the afferent and efferent hypothalamic connectivity. - Discuss the relationship between the mammillary bodies and the limbic system. - Review the anatomy of limbic structures in brain sections ## Case study: Patient HM Patient HM disease is the reason we have a lot of information on the function of the limbic system. - Suffered from temporal lobe epileptic seizures - parts of his temporal lobe was removed to relieve his symptoms. - Removed the amygdala + hippocampus - linked to learning + memory. ### Missing parts are seen. ## The circuit of Papez (1939): Original components: - Hypothalamus (mammillary bodies) - Anterior nucleus of thalamus - Cingulate cortex - Hippocampus - Hippocampus -> hypothalamus -> anterior nucleus of the thalamus which sends signals to the cingulate cortex -> neocortex - Interthalamic adhesion - connects two thalami on two hemispheres together + is a good landmark for the limbic system. ## MacLean's redefinition of the limbic lobe - the limbic system: - **Hypothesis** = These structures are associated with emotional processing ### The limbic structures: - Cingulate cortex - Parahippocampal gyrus = gyrus that leads to the hippocampus - found in the temporal lobe which connects the rest of the neocortex - not from the fornix but cortical areas. - Amygdala - Hippocampus - Hypothalamus ## Olfaction: - Neurones in the nasal cavity (ciliated), use their receptors to determine what we are smelling. - Chemical substances that dissolve in our mucus aid this process. - Very few neurones in the body have the ability to sensory signal. - One of the two regions in the brain that neurogenesis occurs Neurogenesis = formation of new neurones over time ## The sense of smell: - The sense of smell does not play the same important role for adult humans as the senses of hearing and vision. - This does not mean that the sense of smell is insignificant in daily life. - The perception of odors is special by its close association with memories and with emotions and moods. - Presumably, this explains why we usually remember odors so well. - An enormous industry devoted to producing perfumes and other fragrances shows that for humans the sense of smell has an important role in interpersonal communication. ## Senses: ### Traditional senses: - Smell (olfaction) - Sight (vision + ophthalmoception) - Hearing (audioception) - Taste (gustatory + gustaoception) - Touch (tactioceptors) ### Other senses: - Temperature (thermoception), - Kinesthetic sense (proprioception), - Pain (nociception), - Balance (equilibrioception), - Various internal stimuli (e.g. chemoreceptors). ## Cranial nerves – the five senses: | Senses | Cranial Nerves (CNs) | | -------------- | -------------------- | | Smell | Olfactory (I) | | Sight | Optic (II) | | Hearing | Vestibulocochlear (VIII) | | Taste | VII - facial, IX glsph, X vagus | | Touch | Trigeminal (V) | ## Olfactory signal initiation and transmission: - When odour binds to the receptor, the neurones in the cilia send out their axons into glomeruli. - A specific type of neurones expresses a specific type of receptor which terminate into the glomeruli in the olfactory bulb which sends off axons further through the system for central processing - shown in different colours in the image above. - Different neurones terminate at different glomeruli but overall smell is detected by the combined activation of the system. - Olfactory receptor neurons are bipolar cells within the olfactory epithelium. - Ciliated endings contain odourant receptors that detect odours. ## Organisation of the glomerular layer: - Olfactory neurons with the same receptor (ORN) project to the same glomerulus. - Mitral cells (and tufted cells; M/T) synapse onto a single glomerulus - target of olfactory neurones and further project axons for processing - Periglomerular cells (PG) are inhibitory interneurons that synapse within and between glomeruli - modulate function - Granule cells (GR) are inhibitory interneurons that synapse between mitral/tufted cells - modulate function of mitral cells. - Inhibitory neurones prevent the action of excitatory neurones - mitral + tufted cells. - Inhibitory cells use GABA/Dopamine/Glycine as neurotransmitters ## Connections of the olfactory neurones in mammals: - Olfactory neurons send axons to the olfactory bulb which sends information further on. - Olfactory bulb is composed of layers. - Peripheral layer is the glomerular layer where the axons of the olfactory neurons terminate. - Many axons converge on a single glomerulus. - Neurons with different ORs send axons to different glomeruli, whilst neurons with the same receptor contact the same glomeruli. In rats ~ 15 mln olfactory neurons converge onto ~ 1500 glomeruli (10000:1). - This means that activation of different receptors leads to activation of different glomeruli. Combination of activated glomeruli encodes the smell. ## Terminal areas of the main olfactory pathway (in humans): - Humans only have part of the system compared to other animals. - Humans are unable to detect pheromones - don't have the vomeronasal organ which detects hormones in dogs, cats and in some invertebrates. - **Directs sexual behaviour** - **Directs behaviours that control defensive behaviour.** - Humans have a main olfactory system - not the same as accessory olfactory system in other mammals. - Olfactory bulb connects the other side of the brain through the anterior commissure - innervates subthalamic nuclei + hypothalamus -> signal travels to the amygdala -> parahippocampal gyrus and further on. - Uncus = a bump that sticks out of the sagittal aspect of the brain - the primary olfactory cortex lies here. - Primary olfactory cortex - most signals come here before back to the thalamus. - Olfaction is the only sensory system that goes to the cortex before reaching the thalamus. ## Humans vs animals - olfaction:: - Humans can sense over 10.000 different odours. - Detection threshold is as low as parts per million or even billion. - However, in humans smell is largely an aesthetic sense. - Smell in many animals is much more advanced, e.g. in scent-tracking dogs it is ~ 10.000.000 more sensitive than in humans. - Smell directs animals to food, potential mates and away from danger. ## Amygdala: - Involved in fear conditioning, emotional processing, emotional memories. - Almond shaped structure. - Can be subdivided into many subregions - these areas cannot be seen microscopically unless they are specifically stained. - Generally divided into 3-4 nuclei ### Four main subdivisions of amygdala: - Basolateral amygdala - Olfactory (cortical, Co) amygdala - Centromedial (Ce, Me) amygdala and - Extended amygdala - BSTL - bed nucleus of stria terminalis - BSTM - basal nucleus of Meynert ### Main subdivisions of amygdala: - Laterobasal-cortical amygdala - Basolateral / 2. cortical (olfactory) - Centromedial amygdaloid complex - Centromedial - Basal nucleus of Meynert - Bed nucleus of stria terminalis - Extended amygdala ### Four (three?) subdivisions of amygdala: (Note – some people think there's 3-4. Looking at three due to functionality) - **Basolateral amygdala.** - receives highly processed sensory 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. - Relates the the neocortex - **Olfactory (Cortical) amygdala** - Involved in processing of olfactory signals. - In animals, the signals from the pheromonic system terminate in the 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. - Related of the uncus. - Not higher order processing. - **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: - sea horse shaped region ## Amygdala, hippocampus + mammillary bodies. - **Fornix** - fibre connection between hippocampus and the hypothalamus. - **Amygdalo-hypothalamic fibers** (not shown here) pass from amygdala complex to the hypothalamus through the stria terminalis ## Cornus ammonis (CA): - Hippocampus formed during convolution of the cortex within the temporal lobe. - Hippocampus begon allocortex – fewer neuronal layers - Lower order mammals have a larger hippocampus. ## The tri-synaptic circuit of the hippocampus: - Looking at a rat brain – has a large hippocampus - Important in memory + olfaction - Impacts an animals sense of position if impaired. ## The three synapses are able to exhibit synaptic plasticity, such as long-term potentiation; albeit some of the mechanisms involved are quite dissimilar. - The olfactory system is an old system + is capable of generation of new neurones in adulthood. ## The hypothalamus: - Combined of lots of nuclei that have many functions. (NOTE: no need to remember it all) - Small simple structure located just under the thalamus - Subdivided into anterior, middle + posterior hypothalamus. - Mammillary bodies are found in the posterior hypothalamus and hippocampus. - 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 ## Function of the hippocampus: - Primary regulatory of autonomic and endocrine functions. ## Stress reaction: hypothalamic -pituitary-adrenal axis: - Other functions of the hypothalamus: - Fighting - Fleeing - Feeding - Mating ## Hypothalamus in an MRI: ## Main connections of the mammillary nucleus: - **Cingulum** = connections between the cingulate cortex + allocortex. - **Main afferent hypothalamic inputs:** - **Somatic and visceral afferents:** General somatic sensation and gustatory and visceral sensations reach the hypothalamus through collateral branches of the lemniascal afferent fibers and the tractus solitarius and through the reticular formation. - **Visual afferents:** leave the optic chiasma and pass to the suprachiasmatic nucleus. - **Olfaction:** travels through the medial forebrain bundle. - **Auditory afferents:** have not been identified, but since auditory stimuli can influence the activities of the hypothalamus, they must exist. - **Corticohypothalamic fibers:** arise from the frontal lobe of the cerebral cortex and pass directly to the hypothalamus. - **Hippocampo-hypothalamic fibers:** pass from the hippocampus through the fornix to the mammillary body. Many neurophysiologists regard the hypothalamus as the main output pathway of the limbic system. - **Amygdalo-hypothalamic fibers:** pass from the amygdaloid complex to the hypothalamus through the stria terminalis by a route that passes inferior to the lentiform nucleus. - **Thalamo-hypothalamic fibers:** arise from the dorsomedial and midline thalamic nuclei. - **Tegmental fibers:** arise from the midbrain ## Circadian regulation of melatonin production: - Hypothalamus drives production of melatonin which regulates our day + night cycle in many species. ## Main efferent connections of the hypothalamus: - **Descending fibres to the brainstem and spinal cord:** They descend through a series of neurones in the reticular formation. The hypothalamus is connected to the parasympathetic nuclei of the oculomotor (III), facial (VII), glossopharyngeal (IX), and vagus nerves (X) in the brainstem. In a similar manner, the reticulospinal fibres connect the hypothalamus with sympathetic cells of origin in the lateral grey horns of the first thoracic segment to the second lumbar segment of the spinal cord and the sacral parasympathetic outflow at the level of the second, third, and fourth sacral segments of the spinal cord. - **The mammillothalamic tract:** arises in the mammillary body and terminates in the anterior nucleus of the thalamus. Here, the pathway is relayed to the cingulate gyrus. - **The mammillotegmental tract:** arises from the mammillary body and terminates in the cells of the reticular formation in the tegmentum of the midbrain. - **Multiple pathways to the limbic system** ## Hypothalamic functions in terms of lesions: - **Temperature regulation** - Anterior hypothalamus lesion = Hyperthermia - Posterior hypothalamus lesion = Hypothermia - **Food intake** - Ventromedial nucleus lesion = excessive eating (Hyperphagia) - Lateral hypothalamus lesion = reduced eating (Hypophagia) - **Sleep-wake cycle** - Anterior hypothalamus lesion = Insomnia - Posterior hypothalamus lesion = Hypersomnia - **Emotions:** lesion of the ventromedial nucleus = Rage - **Water balance:** lesion of the anterior hypothalamus = Diabetes insipidus