Week 3 - Limbic Systems Flashcards
what is “Le Grade Lobe Limbique”?
the initial components of the limbic lobe for emotions
-cortical area forming rim around diencephalon on medial surface of brain (cingulate cortex, parahippocampal gyrus, olfactory cortex)
what did the Papez circuit hypothesize?
hippocampus is connected to mammillary bodies (hypothalamus) to the anterior nucleus of the thalamus to the cingulate cortex to the hippocampus (and neocortex)
-proven via rabies spread synaptically
does NOT include amygdala
what is the Kluever-Bucy experiment?
removing temporal lobes of aggressive monkeys caused them to become docile, over-eat, eat inappropriate things, hyperoral, hypersexual
-originally agreed with Papez, but then disproved b/c could recapitulate symptoms by removing/damaging amygdala
what are the limbic system and downstream targets known today?
- anterior and mid-cingulate cortex (ACC and MCC)
- amygdala
- hypothalamus
- periaqueductal gray (PAG) matter
- autonomic nervous system
- dorsal raphe nucleus (DRN; serotonin) and locus coeruleus (LC; norepinephrine)
what does the anterior cingulate cortex do?
- store emotional/valenced (emotional weight)information
- recode amygdala (so no primary fear response)
what does the mid-cingulate cortex do?
- select responses (mental or motor)
- predict outcomes and resolve ambiguity
- improvise new behaviors for new problems
what does the amygdala do?
- invests sensory experience with emotional significance (valence)
- most prominently involved in fear
what does the hypothalamus do?
autonomic/hormonal control
what does the periaqueductal gray do?
coordinate autonomic/skeletal behaviors
-surrounds aqueduct in midbrain between 3rd and 4th ventricles
what does the autonomic nervous system do?
skeletal motor output and memory enhancement
what does the locus coeruleus do?
- coordinates responses for fight/flight
- enhances storage of emotional memories
what does the dorsal raphe nucleus do?
regulate mood
what is “emotion”, and the difference between primary and secondary emotions? what are brain structures involved?
emotion = weighting (valencing) object and events with positive or negative responses
primary = reflexive emotions (implicit, don’t need to think about it); linked with autonomic reflexes
- fear is most well-studied
- amygdala, hypothalamus, PAG
secondary = conscious emotions; object and context-dependent
-cortical limbic structures
what mediates the fear response in the amygdala?
the basal-lateral nucleus connects to the central nucleus
what happened to SM, the patient with Urbach-Wiethe disease?
loss of amygdalas bilaterally (due to calcification), but hippocampus intact
- inability to experience fear or recognize fear in faces
- -excessive risk taking, odd relations and financial decisions
- no motor or sensory defects; no intelligence, memory, or language deficits
why would the fear response be intact if the connection between the auditory cortex and amygdala was cut?
amygdala gets input from both auditory cortex (which gets it from medial geniculate nucleus), and directly from MGN
-since the thalamic message has no cortical processing, thus dominating initial primary response to fear
steps in how amygdala is involved in fear perceptions, ANS responses, and memory
- fear-invoking stimulus from any sensory modality (visual, auditory, touch, etc.)
- stimulus is perceived
- input goes directly from LGN to amygdala (and visual cortex), activating fear response
- activates both cortex and output pathways - expression of fear somatic and viscerally (fight or flight response)
- memory gets encoded in amygdala and cortex
- memory is dramatically enhanced in presence of NE for LC
what does electrical stimulation of PAG (or hypothalamic nuclei that project to it) do? how are responses organized? does it have memory?
evoke complex and fully integrated behaviors
- stimulating different parts of PAG makes different classes of behaviors
- responses are organized by PAG projections into different parts of ANS and skeletomotor systems to produce fully coordinated outputs
- PAG has no memory, since it’s controlled by higher brain regions
what would tumors to the lateral hypothalamus cause emotion-wise?
affective defense is projected to PAG
what would tumors to the ventral medial hypothalamus cause emotion-wise?
quiet biting/quiescence is projected to PAG
what is sham rage and how is it produced?
fully integrated rage w/o external control
-can be produced by stroke/tumors to hypothalamus/PAG
how does the PAG regulate ANS?
projections to the nucleus of solitary tract, dorsal motor nucleus of vagus, and intermediolateral nucleus
-circuit produces ANS sensory input during arousal via somatic markers
what is the HPAA?
hypothalmic control of hormone response via pituitary, adrenals, and amygdala
what does amgydala and limbic cortex do in HPAA?
drives PVN of hypothalamus to secrete CRH into portal veins
- evokes release of ACTH from pituitary to evoke release of cortisol from adrenal cortex
- cortisol binds glucocorticoid receptors to
- -increase glucose levels/metabolism
- -increase AA metabolism
- -increase fat breakdown
- -increase memory
what drives the PVN-HPA axis?
norepinephrine from locus coeruleus
what is the anterior cingulate cortex involved in?
AFFECT; stores long-term emotional memories and operates through ANS via projections to nucleus of solitary tract and dorsal motor nucleus of vagus
what is the midcingulate cortex involved in?
motivated behavior and response selection (resolves conflict and regulates skeletomotor output)
- anterior part is active during fear, and operates thru spinal projections to skeletomotor system
- extensive projections to striatum, red nucleus, pontine nuclei, and CN motor nuclei for somatomotor driving of alpha motor neurons
which is more involved in emotion, ACC or PCC?
ACC
-but this perigenual region (around genu of corpus callosum) is selectively vulnerable to emotional diseases like depression
what does PET show when remembering sad, scary, and happy events?
activation of different parts of limbic system
- fear = anterior MCC
- sadness = ventral ACC
- happiness = rostral ACC
what does electrical stimulation of MCC evoke?
complex skeletomotor responses adapted to context (activities that are valenced and context dependent)
what is the facial region of ACC? where does it project?
critical for emotional awareness
- projects to facial motor nuclei for facial expression
- near ACC/MCC border
steps in how amygdala is involved in fear perceptions, ACC and facial expressions
- visual stimulus
- visual input and memory activate amygdala
- upstream ACC and downstream PAG activation
- internal fear
- ACC activates PAG more
- activates face area at ACC/MCC border
- projects to facial motor nuclei
- generates facial surprise/fear
what is a key upstream and downstream coordinator of the limbic system?
the locus coeruleus (driven by norepinephrine)
what kind of input is the LC driven by?
amygdala and limbic cortex input drives it
-is reciproccally connected with paraventricular nucleus in hypothalamus (which also gets input from amygdala and limbic cortex) for emotional memory formation
what does storage of emotionally valenced memories in amygdala and ACC depend on?
norepinephrine released by LC
where is the LC located?
in the tegmentum of metencephalon (pons)
how does LC/NE integrate limbic motor systems?
- NTS/PVT mediate heart rate responses in sACC/central amygdala
- PAG:NE selects F-F
- PVN drives HPA axis via NE, ACTH, cortisol
- enhances amygdala processing and memory
what are limbic system disorders?
conduct, criminal psychopathy, sociopathies
-clinically important are mood disorders, especially depression
how does glucose usage change in depressed patients?
decreases specifically in ACC, particularly at genu of CC (area of connectivity with amygdala)
-indicates that function of cingulate is aberrant
what is the general treatment strategy for depression?
modulation of NE and 5HT (serotonin)
-SSRI (selective serotonin reuptake inhibitor) is one of the most effective treatments for depression
what is the dorsal raphe nuclei?
located in midbrain (midline of brainstem), with serotonergic (5HT) neurons
- project broadly to brain, but enriched to limbic in forebrain (amygdala, insula, and ACC)
- determine tonic activity
what happens if there’s a short form of the 5HT transporter (s5HTT)
- reduced functional interaction of ACC and amygdala, thus shrunken
- amygdala uncontrolled by ACC associated with enhanced fear/anxiety
- higher risk for developing depression
why does it take so long for 5HT therapy via SSRIs to take effect?
- at steady state, 5HT activity in ACC is decreased in depressed patients
- treatment with SSRIs initially has little effect on amount of 5HT in ACC
- levels are increased at both level of DRN and ACC, but these elevated levels cause DRN neurons to decrease 5HT release in ACC due to DRN autoreceptors - over time, autoreceptors are internalized and decreased, thus giving rise to higher levels of 5HT and ACC
what are the receptors on DRN involved in depression called?
5-HT autoreceptors
-regulate presynaptic cell to figure out how much serotonin to release
what shows substantial improvements in patients who have intractable depression?
deep brain stimulation
