Limbic system and olfaction

Question 1

Overview of olfaction and limbic system

Answer 1

• Limbic system comprised of amygdala, hippocampus and septum (also cingulate gyrus, nucleus accumbens, hypothalamus)
• Olfactory system senses chemosensory stimuli disolved in nasal mucus and transmits the info to the amygdala and piriform (primary olfactory) cortex
• Main olfactory system (ours predominantly) detects volatile (airborne) stimuli, accessory olfactory system (not predominantly in humans) detects non-volatile stimuli related to social cues (pheromones)

Question 2

Peripheral olfactory detection 1

Answer 2

• Airborne stimuli in external nare mucus contact olfactory receptors (specialized bipolar neurons w/ apical tuft of cilia and GPCR odorant receptors)
• We have >1000 different receptors, each for one odor. Each olfactory receptor expresses a single odor receptor
• Neurons w/ the same odor receptor all send projections to the same glomerulus in the olfactory bulb

Question 3

Peripheral olfactory detection 2

Answer 3

• Olfactory receptor neurons only last 30-60 days (replenished by stem cells in nasal cavity), and are located in olfactory epithelium
• Projections of olfactory receptors form CN I to reach the glomeruli of common odor receptor input, in the olfactory bulb
• Glomeruli project to mitral cells in the olfactory bulb (olfactory tract)

Question 4

Central olfactory processing

Answer 4

• Mitral cells in olfactory bulb project to central olfactory targets thru the lateral olfactory tract (ipsilateral, unlike other sensory systems)
• Projections terminate on the piriform cortex (primary olfactory), amygdala and entorhinal cortex
• These targets eventually send projections to the hippocampus, hypothalamus, thalamus, and cortex

Question 5

Piriform cortex

Answer 5

• 3 layered allocortex, responsible for olfactory discrimination thru connections w/ lateral orbitofrontal cortex
• This connection both directly and indirectly (via dorsomedial thalamus)

Question 6

Corticomedial amygdala and entorhinal cortex

Answer 6

• Corticomedial amygdala receives and integrates socially-relevant inputs from different sensory systems
• Connections are important for social behavior, sexual behavior, aggressive behavior, and parental behavior
• Has receptors for gonadal steroids and connections w/ relevant hypothalamic nuclei
• Connections w/ entorhinal cortex allows olfaction to influence memory, and contributes to the emotional response to odors

Question 7

Anosmia and hyperosmia

Answer 7

• Anosmia: loss of smell, can be developmental or the result of tumors, trauma, or metabolic diseases. Also compromises the sense of taste
• Hyperosmia: develops during pregnancy and w/ some psychiatric d/o

Question 8

Regions and function of amygdala 1

Answer 8

• Corticomedial amygdala: integrates olfactory info w/ memory/emotions (endocrine signals and ascending somatosensory info) to modulate social behavior
• Has projections to hypothalamic nuclei via stria terminalis
• Basolateral amygdala: larger and is involved in learned emotional responses to sensory stimuli (mostly negative emotions like fear and anxiety), connects to brainstem nuclei involved w/ autonomic responses in emotion

Question 9

Regions and function of amygdala 2

Answer 9

• Basolateral amygdala receives info from sensory (visual and auditory), hippocampus, cingulate, prefrontal, and parietal cortices
• These inputs shape emotional responses to threat, hunger, and social interaction
• Is related to associative memory since most of these responses are learned
• Projections of the basolateral amygdala to orbitofrontal cortex are important for perception of memory
• Projections to hypothalamus contribute to expression of emotion

Question 10

Clinical implications of amygdala lesions

Answer 10

• Basolateral amygdala damage results in kluver-bucy syndrome: lack of emotional response, hyperorality (eating shit) due to loss of visual recognition, and hypersexuality. Very rare
• Anxiety and PTSD: Very common. Due to learned hyper vigilance to environmental stimuli. Rx only unlearn the fear memories
• Autism in part due to dysfunction of amygdala

Question 11

Septum and nucleus accumbens 1

Answer 11

• Septum extends medially btwn the LVs, dorsal to hypothalamus and anterior to thalamus
• Septal nuclei have connections w/ the hippocampus and amygdala (also other limbic regions)
• Lateral septum is important for social behaviors, mostly aggression (testosterone receptors) and pair-bonding (vasopressin neurons)

Question 12

Septum and nucleus accumbens 2

Answer 12

• Medial septum contains large and abundant cholinergic neurons, which have wide-spread connections including to forebrain to regulate attention and cortical arousal
• Nucleus accumbens: key element of ventral striatum. The NA and midbrain ventral tegmental area (VTA) together form the mesolimbic DA system
• DA neurons in VTA project to NA to produce reward. The NA then projects to the basal ganglia to then facilitate reinforcement of habit to get the reward
• This pathway is largely implicated in drug abuse

Question 13

Hippocampus 1

Answer 13

• Critical for learning and memory, comprised of a 3-layered allocortex: dentate gyrus, corpu ammon’s (CA1-4), and subiculum
• Dentate gyrus and CA folded onto one another
• Hippocampus has bidirectional connections w/ other brain regions thru the fornix and perforant pathway
• Movement of info: afferents enter the dentate gyrus and move to CA4->CA1, then to subiculum, which is major source of hippocampal efferents, which feeds back to entorrhinal cortex

Question 14

Hippocampus 2

Answer 14

• Hippocampus connects (via fornix) to septum, thalamus, hypothalamus, and mammillary bodies
• Also connects (via perforant pathways) to temporal association areas
• One of the most active and dynamic brain regions, has ongoing neurogenesis and high metabolic activity
• Thus has low seizure threshold (temporal lobe epilepsy) and sensitive to ischemic change

Question 15

Function of hippocampus

Answer 15

• Important for declarative memory: memory of facts, experiences, and info
• Damage interferes w/ formation of new memories (anterograde amnesia), but does not affect existing long-term memory (no retrograde amnesia)
• Thus it is required for memory formation, but not for storage of long-term memory
• AD pts largely have loss of hippocampal neurons
• Korsakoff’s syndrome: memory loss w/ confabulation. Occurs in chronic alcoholism
• Lesions in medial dorsal thalamus can give korsakoff’s syndrome