17. The Limbic System
function:
responsible for learning, memory, emotions ·
receives from
sensory and association cortices ·
influences ANS
via hypothalamus ·
influences rational behaviour: you need to have an emotional response to
the sabertooth tiger, not just see it! * the neocortex does not
project to ANS directly *all limbic
system structures project directly/indirectly to hypothalamus (part of limbic system) - only hypothalamic output to ANS: 1. reticulo-spinal tract, 2. hypothalamic-spinal tract - ANS feeds back to limbic system: quadriplegics show gradual blunting of
emotional affect limbic associations 1. ANS (see above) 2. olfaction: smell is integrated with
memory, emotion, sexuality; associated with: 1. septal nuclei; 2. amygdala; 3. temporal lobe nuclei 3. reticular formation: association with
(deteriorates with Alzheimer’s,
normal aging, Down’s, Parkinson’s, JCD, Pick’s, Korsakoff’s
à
emotional changes) 4. orbitofrontal cortex: lesions to
this (or DM) à a.
loss of initiative (Alzheimer’s) b.
socially unacceptable behavior (Alzheimer’s) c.
severe depression (Huntington’s,
Alzheimer’s) d.
lack appreciation of consequences 5. extrapyramidal system: tremor
associated with emotional stress 6. limbic system structures
show the lowest threshold for seizures (auras: fear, olfactory, stereotyped
movements) |
I.
Anatomy
a.
Hippocampal formation
i.
Hippocampus (“sea horse”)
- old cortical
area
-
connected to mammillary bodies (hypothalamus) via fornix
ii.
Dentate gyrus
iii.
Subiculum
b.
Limbic Lobe (“on
the edge”)
i.
Cingulate Gyrus
ii.
Orbitofrontal Cortex
iii.
Parahippocampal Gyrus
iv.
Septal Nuclei
c.
Limbic system
i.
Hypothalamus
ii.
Hippocampus
iii.
Nuclei of
Thalamus (AN, DM, LD)
iv.
Cingulate Gyrus
v.
Parahippocampal gyrus
vi.
Septal nuclei
vii.
Habenular nuclei
viii.
amygdala
ix.
some neo-cortical areas
(frontal and temporal)
1.
entorhinal cortex (Area 28)
d.
Pathways
- integrate
memory with emotion
i.
Papez Circuit
-
integrates emotion with explicit
memory
ii.
Dorsomedial nucleus (thalamus)
-
receives from most limbic structures
- output à orbitofrontal cortex
-
integrates emotion with implicit
memory
II. Biochemistry
a.
Neurotransmitters
i.
Glutamate
-
implicated in seizure focus (glutamate toxicity) can à bilateral (callosal) lesions
(therefore it is important to control seizures)
- limbic system (entorhinal cortex,
hippocampus, dentate gyrus)
ii.
5HT (serotonin)
- raphe nuclei (isolated reticular
formation nuclei)
- effects: promotes a feeling of well-being and sleep; reduces aggression
and compulsion; elevates
pain threshold
iii.
NE
-
increases feelings of well-being; reduces compulsion; may induce anxiety
iv.
Dopamine
- midbrain (substantia nigra, VTA)
-
increases feelings of well-being; increases aggression, alertness, sexual excitement; reduces
compulsion
v.
ACh
- basal forebrain neurons (nucleus basalis of Meynert), septal nuclei
-
associated with memory
vi.
GABA
- integrative interneurons
- reduces anxiety and
compulsion; elevates pain
threshold
b.
Classic Psychoactive drugs
i.
Major tranquilizers (= anti-psychotics = neuroleptics)
1.
Dopamine blockers
-
control psychotic behaviour
- L-dopa (Parinson’s treatment) is contraindicated in individuals with mental instability
a.
Phenothiazines
b.
Butyrophenones
2.
Atypical anti-psychotic drugs
- fewer extrapyramidal motor system
effects
- dopamine antagonists
a.
Clozapine
b.
Risperidone
ii.
Minor tranquilizers (= anti-anxiety drugs)
1.
benodiazepines (valium)
- valium+alcohol à lethal respiratory combination
- also anti-convulsant
- (GABA enhancer)
iii.
Anti-depressants
1.
Monoamine oxidase (MAO)
inhibitors
-
increase endogenous levels of monoamines (NE, 5HT)
- also block tyramine (found in cheese) metabolism à hypertension à hemorrhagic
stroke
2.
Tricyclic
anti-depressants
-
operate on monoaminergic systems (NE, 5HT)
- potent anti-cholinergic (à dry mouth)
c.
Designer drugs
i.
Prozac
- SSRI (selective serotonin
reuptake inhibitor)
- impacts “reactive depression”, obsessive “depressed”
personalities
ii.
Zoloft
- SSRI
- works on those for whom Prozac does not work
iii.
Welbutrin
- unknown neurochemical mechanism
d.
Social drugs
i.
Amphetamine
-
stimulates catecholaminergic neurons in limbic system
and reticular formation
- may à paranoid psychosis (treat with anti-psychotic agents)
ii.
Cocaine
- monoamines à euphoria, tolerance
- impacts: 1. MFB, VTA, nucleus accumbens
septi
III. Neuroimmunology
- limbic system plays a critical role in development of coping skills (“emotional
thermostat”)
- limbic system affects: ANS (hypothalamic projections à sweat with fear, etc.); reticular formation (à alert with fear)
STRESS
- physical and psychological threats treated similarly by
limbic system
1.
Endocrine
response/Immune response
a.
increased:
i.
endorphins (blunt
physical and mental pain)
ii.
enkephalins
iii.
ACTH release
(fight or flight) à catecholamines (epinephrine and norepinephrine) and cortisol
release by adrenals
- high cortisol decreases natural immune
response (decrease: natural killer cells, T cells, DNA repair; autoimmune
increase)
- high cortisol seen in depressed
patients
2.
Cardiovascular
response (mediated by catecholamine increase)
- chronic stress damages heart muscle (non-ischemic), increases
CAD, muscular spasms of artery walls
-
increases platelet clumping
-
increases cholesterol build-up