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Limbic system
Limbic system
from Latin limbus, means "border" or "belt„
Functions: emotion, behavior, long-term memory, olfaction
Cortical region
cingular
orbitofrontal
insular
medial prefrontal
Subcortical region
insula
anterior thalamic nuclei
septal area
nucleus accumbens
hippocampus, amygdala
mammilary body
Papez circuit
the major pathways of the limbic system - involved in the cortical control
of emotion, plays a role in storing memory
Papez discovered the circuit after injecting rabies virus into a cat's
hippocampus and monitoring its progression through the brain.
(Associative
cortex)
– cingulate cortexentorhinal cortex –
hippocampus –
fornix hypothalamus MB
– anterior
thalamus –
cingulate cortex
Hippocampus
From Greek
hippos = horse, kampos = sea monster)
• part of the telencephalon
(forebrain)
• located inside the medial
temporal lobe of the
cerebral cortex
• The strongest connections
of the hippocampus are
with the entorhinal cortex
(EC).
Information flows into and through the
hippocampus by three principal pathways
1. the perforant pathway from the entorhinal cortex to granule cells of the
dentate gyrus;
2. the mossy fiber pathway from the granule cell of the dentate gyrus to the
pyramidal cells of the CA3 region of the hippocampus; and
3. the Schaffer collateral pathway from the CA3 region of the hippocampus
to the CA1 region of the hippocampus.
Function
• storing and processing spatial
information (London's taxi
drivers – larger hippocampus)
• important role in the formation
of new memories about
experienced events (episodic or
autobiographical memory)
• Damage to the hippocampus
does not affect the ability to
learn new skills (playing a
musical instrument)
Place cells
Patient H.M.
the 1950s - HM (patient) (Henry
Gustav Molaison (1926–2008)
- memory-impaired patient
In 1953 – William Scoville
(surgeon at Hartford Hospital)
removed two-thirds of his
hippocampus,
parahippocampal gyrus, and
amygdala (for diagnosed
focal epilepsy in medial
temporal lobes)
After the surgery - severe
anterograde amnesia (he
could not commit new events
to long-term memory).
His ability to form long-term
procedural memories was
intact - he could learn new
motor skills, despite not
being able to remember
learning them.
Long Term
LTPPotentiation
(LTP)
• long-lasting improvement
in communication
between two neurons
that results from
stimulating them
simultaneously
• one of the major cellular
mechanisms that
underlies learning and
memory
• electrical stimulation to a
fiber of the perforant
pathway caused an
excitatory postsynaptic
potential (EPSP) in a cell
of the dentate gyrus
Parahippocampal gyrus
• a grey matter cortical region of the brain that
surrounds the hippocampus
• important role in memory encoding and retrieval
• The anterior part of the gyrus includes the perirhinal
and entorhinal cortices
Grid cells
Amygdala
• from Greek = Almond
• primary role in the
processing and memory
of emotional reactions
• related to many
psychological disorders
(social phobia, autism,
bipolar disorder)
• Nuclei:
– basolateral complex
(lateral, basal, accessory
basal nuclei)
– centromedial nucleus
– cortical nucleus
Amygdala
• Connections to:
– hypothalamus - important
activation of the sympathetic
nervous system
– thalamic reticular nucleus increased reflexes
– nuclei of the trigeminal nerve
and facial nerve - facial
expressions of fear
– ventral tegmental area, locus
coeruleus, and laterodorsal
tegmental nucleus - activation
of DA, NE and E
• Inputs from:
– from the olfactory bulb and
olfactory cortex to the cortical
nucleus - sense of smell and
pheromone-processing.
– from the sensory systems to
the lateral amygdalae
Associative cortex – cingular cortex – hippocampus –
hypothalamus – thalamus – cingular cortex
center for identification of danger
Role of amygdala
Rage
Fear
Immediate reaction on threat
Sensory cortex
„Long route“
30 – 40 ms
„Short route“
Senory
thalamus
Emotional stimulus
12 ms
Amygdala
Emotional reaction
Conditioned
fear
(emotional learning)
memory is stored in
amygdala nuclei
Medina et al. 2002
Syndrom Klüver-Bucy
Bilateral ablation of anterior
temporal lobes (including
amygdala) (1939)
•
Hyperorality
•
Loss of fear
•
Decreased aggression
•
Changed alimentary
behavior
•
Hypersexuality
•
Curiosity about
everything, forgets rapidly
VTA - located in the mesencephalic part of the brain stem
There are dopamine-secreting neurons whose axons end in the
nucleus accumbens (mesolimbic dopaminergic pathway) – reward
Reduction of D2 receptors- reward deficiency syndrome
Reward centre
Meso-cortico-limbic dopaminergic
system :
Olds and Milner. Intracranial selfstimulation (1954)
José Delgado
1965
Septal region
anteriorly to the
thalamus
this area is associated with different kinds of pleasant
sensations, mainly those related to sexual experiences
Generator of theta rhythm
Septal nuclei provide essential interconnections between
various parts of the limbic system
Hypothalamus
NTS: from the vagus
(blood pressure and
gut distension)
circumventricular
organs: lack a
blood-brain barrier
(osmolarity, toxins)
amygdala,
hippocampus,
olfactory cortex
Limbic
system
A division of the diencephalon
Reticular formation: from
the spinal cord (skin
temperature)
H
Retina: from
retinohypothalamic tract to
SCN (photoperiod)
Endocrine
system
Autonomic nervous system
Hypothalamus
12 important nuclei:
• MEDIAL PREOPTIC NUCLEUS
– Regulates the release of gonadotropic hormones from the
Adenohypophysis
• SUPRACHIASMIC NUCLEUS
– Receives input directly form the retina.
– Plays a role in regulating circadian rhythm
• ANTERIOR NUCLEUS
– Important in temperature regulation
– Stimulates PNS
– It’s destruction results in hyperthermia
• PARAVENTRICULAR NUCLEUS
– Synthesizes ADH- and thus regulates water balance
– Releases oxytocin
– Synthesizes CRH - stress
• SUPRAOPTIC NUCLEUS
– Synthesizes ADH- and thus regulates water balance
– Releases oxytocin
• DORSOMEDIAL NUCLEUS
– When stimulated in animals, causes savage behavior!
• VENTROMEDIAL NUCLEUS
– Is the satiety center- this means that once it is stimulates, it inhibits the
urge to eat
• LATERAL HYPOTHALAMIC NUCLEUS
– Induces eating
• ARCUATE (INFUNDIBULAR) NUCLEUS
– Contains neurons that produce factors that stimulate or inhibit action of
hypothalamus
– Contains neurons that produce Dopamine
• MAMILLARY NUCLEUS
– Lesions (Korsakoff syndrome) are associated with thiamine deficiency
and alcoholism – anterograde amnesia
• POSTERIOR HYPOTHALAMIC NUCLEUS
– Plays a role in thermoregulation
– Lesion results in poikilothermia
• VENTROLATERAL PREOPTIC NUCLEUS (VLPO) - regulation of
sleep and wakefulness
Hypothalamus - functions
•
AUTONOMIC
– Stimulation of the ANTERIOR HYPOTHALAMUS: excitatory effect on
parasympathetic system (trophotropic)
– Stimulation of POSTERIOR HYPOTHALAMUS: excitatory effect of
sympathetic system (ergotropic)
•
THERMOREGULATION
– Stimulation of ANTERIOR HYPOTHALAMUS: regulates and maintains
temperature
– Stimulation of POSTERIOR HYPOTHAMUS: produces and conserves
heat
•
WATER BALANCE
– Paraventricular (Supraoptic) nuclei synthesize ADH and control kidney
water excretion
•
FOOD INTAKE
– Stimulation of VENTROMEDIAL NUCLEUS inhibits the urge to eat
– Stimulation of LATERAL HYPOTHALAMIC NUCLEUS induces the
urge to eat
Cerebral cortex
•
•
•
Left and right hemisphere
Lobes- frontal, parietal, occipital,
temporal
Sulci et gyri
Phylogenetically older – allocortex
(10 %) – does not receive thalamic
input
paleocortex (parahippocampal
gyrus, olfactory cortex
archicortex (hippocampal formation:
hippocampus, dentate gyrus) 3-4
•
layers
Phylogenetically younger - neocortex
(90%) – 6 layers
Lamina molecularis
Input from nonspecific thalamus
Lamina granularis
externa
Lamina pyramidalis
externa
Interhemispheric
connection
Lamina granularis
interna
Input from specific
thalamus
Lamina pyramidalis
interna
Betz cells (to brain
stem and spinal cord)
Lamina multiformis
(to thalamus)
Output fibers
Associative
connections
Surface 0.25 m2
Thickness
2 – 5 mm
Columnar organisation
Column – functional unite
visual cortex
Brodman's areas
Motor cortex
Sensory cortex
Associative cortex
Primary
Secondary
Tertiary
Sensory areas
• Primary
sensory areas receive sensory
inputs from the
thalamus
• In general, the
two hemispheres
receive
information from
the contralateral
side of the body.
Topographic maps - the organization of sensory maps in the cortex
correspond with the sensing organs
the primary visual cortex - retinotopic map
the primary auditory cortex - tonotopic map
the primary somatosensory cortex - somatotopic map (homunculus)
Somatosensory cortex
• The postcentral gyrus - the
sense of touch
• Primary somatosensory cortex
- BA 3, 1 and 2
• Secondary somatosensory
cortex – BA 5, 7
Lesions:
Loss of vibration, proprioception, fine touch
It could also reduce nociception, thermoception and crude touch (but these
are more in insular cortex and cingulate gyrus).
Agraphesthesia - disorder of directional cutaneous kinesthesia (writing on
skin)
Astereognosia (tactile agnosia) - impaired ability to recognize or identify
objects by touch alone
Hemineglect - ignoring the contra-lesional side of their body (no shaving,
no make-up)
Motor cortex
• The primary motor cortex
(M1) - the posterior portion of
the frontal lobe.
• Precentral gyrus = BA 4
• M1 contains large neurons
known as Betz cells (pyramidal
cells in layer V) - long axons to
alpha motoneurons in the
spinal cord.
• Supplementary motor area
•
•
BA 6 - on the medial face of the
hemisphere, just in front of primary
motor cortex (premotor cortex)
Function:
– planning of motor actions
– bimanual control
– In contrast to M1 - actions that
are under internal control
(performance of a sequence of
movements from memory)
– involved in retrieving the
sequence of movements
• The corticospinal (pyramidal)
tract
– About half of its fibres arise
from the primary motor cortex.
– Other contributions come from:
• supplementary motor area
• premotor cortex
• somatosensory cortex
• parietal lobe
• cingulate gyrus
Visual cortex
• Located and around the calcarine
fissure in the occipital lobe.
• Anatomically - Brodmann area BA 17
• 6 layers - Layer 4, which receives
most visual input from the lateral
geniculate nucleus
• Primary visual cortex – V1 (visual
orientations and colors)
• Extrastriate visual cortical areas –
V2, V3, V4, V5 – BA 18, 19 (attention,
working memory, and reward
expectation)
• Function:
– The dorsal stream ("Where
Pathway" or "How Pathway„) motion, object locations, control of
the eyes and arms
– The ventral stream ("What
Pathway„) - form recognition and
object representation, storage of
long-term memory.
Auditory cortex
• Anatomically – BA 41, 42
• Inputs from the medial
geniculate nucleus of the
thalamus.
• Function:
– Primary auditory cortex in the superior temporal
lobe -sensation of basic
characteristics of sound
(pitch and rhythm)
– Additional areas - in the
frontal and parietal lobes processing of acoustic
signals (distinguished
between speech, music,
noise)
Association auditory cortex
Broca's area (pars opercularis and
pars triangularis of the inferior
frontal gyrus) BA 44, 45
– responsible for speech
production
– Broca’s (motor) aphasia –
understands, but problems
with fluent speaking
In the left
hemisphere
Wernicke's area (where the temporal
lobe meets the parietal lobe)
posterior part of BA 22
– responsible for understanding
– Wernicke’s (receptive, sensory)
aphasia – can speak, but does not
understand
•
In the left hemisphere (in most
people specialized for language
skills)
In the left
hemisphere (95%)
Association areas
Parieto-occipito-temporal:
integration of visual, auditory and
somatosensory modalities
continuous analysis of spatial
coordinates of all parts of the body
area for language comprehension
(Wernicke's sensory speech center)
understanding of written text (gyrus
angularis)
Unilateral
neglect
Association areas
Frontal lobe
• Reaches full maturity around age 25
– increased myelin in the frontal lobe white matter of young
adults compared to that of teens
– A typical onset of schizophrenia in early adult years correlates
with poorly myelinated (inefficient) connections between cells
in the fore-brain.
• The frontal lobe contains most of the dopamine-sensitive
neurons in the cerebral cortex.
• Functions (involved in higher mental functions):
– to recognize future consequences resulting from current
actions
– to choose between good and bad actions
– override and suppress unacceptable social responses
– determine similarities and differences between things or
events
Phineas Gage
1848
Damage of frontal lobes
• Impaired mental flexibility and spontaneity, but
IQ is not reduced.
• Talking may increase or decrease dramatically.
• Increase of risk taking behavior.
• Socialization can diminish or increase.
• Orbital frontal lobe damage can result in
perverse sexual habits.
• Diminished creativity and problem solving
skills.
• Frequent distractions.
Prefrontal cortex
• the anterior part of the frontal lobes
• defined by the presence of an internal granular layer IV
(in contrast to the agranular premotor cortex)
• Parts:
–
–
–
–
–
–
orbitofrontal (OFC) and ventromedial areas (vm-PFC)
dorsolateral prefrontal cortex (dl-PFC)
anterior and ventral cingulate cortex
ventrolateral cortex (vl-PFC)
medial prefrontal cortex (m-PFC)
anterior prefrontal cortex (a-PFC).
• Function:
–
–
–
–
planning complex cognitive behaviors
personality expression
decision making
moderating correct social behavior
Psychosurgery
• In the early 20th century
- Portuguese neurologist
Egas Moniz developed a
medical treatment for
mental illness
• Damage of the pathways
connecting the frontal
lobe and the limbic
system
• Frontal lobotomy
successfully reduced
distress, but suppressed
emotions, volition and
personality.
Association areas
Two brains
• Left hemisphere
analytic
rational
verbal
• Right hemisphere
synthetic
intuitive
non-verbal