AMYGDALA - keywords
amygdala and emotion in a specific limbic subsystem
emotion
amygdala are a nodal point for investing emotion in
sensory experiences, used for long term executive
planning (motivation); other nuclei involved in emotion
are paraventricular thalamus, prefrontal cortex, nucleus
accumbens septi
amygdala are a crucial relay in the limbic subsystem that
ends in an emotional working memory in the orbitofrontal
and medial prefrontal cortex where feelings (e.g. fear and
anger but also other emotions) are encoded; they
supervise encoding for some form of implicit memory
core affect
motivation (drive
based on memory)
arousal
+
valence
+
-
-
associative learning occurs by coupling of a neutral stimulus (conditional shock or cue —> thalamus) to an
inforcer like touch or pain (a conditional stimulus —> parabrachial nucleus and sensory cortex), both
sending information to the amygdala
hippocampus
conditioned shock
(cue) like e.g a sound
(neutral input)
basal amygdala
thalamus
unconditioned
shock like e.g pain
(reinforcer)
LTP
lateral amygdala
LTP
central amygdala
sensory cortex and
parabrachial nucleus
amygdalar subnuclei
form different
microcircuits for
specific issues
effector nuclei: ventral forebrain,
hypothalamus, brainstem
Altman J, Bayer SA (2015) Development of the human neocortex: a review and interpretation of the histological record. A Free eBook from the
Laboratory of Developmental Neurobiology, Inc. www.neurondevelopment.org © 2015. Janak PH, Tye KM. From circuits to behaviour in the
amygdala. Nature. 2015 Jan 15;517(7534):284-92. doi: 10.1038/nature14188.
Gloor P (1997) The temporal lobe and limbic system. Oxford University press.
Mulc D, Smilović D, Krsnik Ž, Junaković-Munjas A, Kopić J, Kostović I, Šimić G, Vukšić M. Fetal development of the human amygdala. J Comp
Neurol. 2024 Jan;532(1):e25580. doi: 10.1002/cne.25580. PMID: 38289194.
Netter FH (1986) The CIBA Collection of Medical Illustrations. Vol. 1. Nervous System. Part I: Anatomy and Physiology. West Caldwell, NJ: CIBA
Pharmaceutical.
Nieuwenhuys R, Voogd J, van Huijzenz C (1988) The human central nervous system. Third revised edition. Springer-Verlag. Digital version by
Martin Hirsch named ‘Interbrain’.
Paxinos G, Mai JK (Eds.), The Human Nervous System, second ed. Elsevier, Amsterdam, 2004.
Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia A-S, White LE (2012) Neuroscience. Fifth edition. Sinauer associates.
Roesler R, McCaugh JL (2022) The entorhinal cortex as a gateway for amygdala influences on memory consolidation. Neuroscience 497; 86-96.
Smith CG, van der Kooy DJ (1985) Basic Neuroanatomy. 3rd Edn. Toronto: Collamore Press.
ten Donkelaar HJ, Lammens M, Cruysberg JRM, Hori A, Shiota K, Verbist B (2006) Development and developmental disorders of the forebrain. In:
ten Donkelaar HJ, Lammens M, Hori A (eds) Clinical Neuroembryology: development and developmental disorders of the human central nervous
system. Springer, Berlin/ Heidelberg/New York, pp 345–428.
anatomy of the amygdala in a coronal section
adpated from
Nieuwenhuys et al.1988
1 Indusium griseum
2 Body of the caudate nucleus
3 Anterior nucleus of the thalamus
4 Reticular nucleus of the thalamus
5 Ventral anterior thalamic nucleus
6 Putamen
7 Globus pallidus, external segment
8 Globus pallidus, internal segment
9 Posterior nucleus of the hypothalamus
10 Ventromedial nucleus of the hypothalamus
11 Lateral area of the hypothalamus
12 Tuberal nuclei
13 Infundibular nucleus
14 Innominate substance
15 Central nucleus of the amygdaloid body
16 Accessory basal nucleus of the amygdaloid body
17 Medial nucleus of the amygdaloid body
18 Cortical nucleus of the amygdaloid body
19 Basal nucleus of the amygdaloid body
20 Lateral nucleus of the amygdaloid body
21 Ammon’s horn
22 Cingulum
23 Lateral longitudinal stria
24 Medial longitudinal stria
25 External medullary lamina
26 Internal medullary lamina
27 Stria medullaris
28 Internal capsule, posterior limb
29 External capsule
30 Extreme capsule
31 Lateral medullary lamina
32 Medial medullary lamina
33 Thalamic fascicle
34 Lenticular fascicle
35 Column of the fornix
36 Ansa lenticularis
37 Optic tract
38 Anterior commissure
connections of the amygdala
M
3
ST
6
10
2
13
VA
11
7
9
8
5
FU
1
2
3
4
5
6
7
amygdala
stria terminalis
mediodorsal thalamic nucleus
10
corpus mammillare
14
hippocampus
septal nuclei + nu. accumbens
diagonal band (Foville)(external aspect of part of the ventral
amygdalofugal pathway)(part of extended amygdala)
8 inferior thalamic pedicle
9 lateral olfactory stria
10 fasciculus uncinatus (to orbital and medial prefrontal cortex)
11 tuberculum olfactorium
12 commissura anterior
13 medial forebrain bundle
14 amygdalo-neocortical connections
VA ventral amygdalofugal pathway
ST stria terminalis
FU fasciculus uncinatus
M foramen of Monro
Me medial nucleus
C cortical nucleus (olfactory)
Ce central nucleus (hypothalamus and stem)
BL basolateral complex (temporal and frontal cortex) B + L + AB
PG
4
14
serial connections: basolateral to basal,
basal and basolateral to central
parallel connections directly to central
efferent tracts of the amygdala
1
2
3
4
5
6
7
amygdala
stria terminalis
mediodorsal thalamic nucleus
corpus mammillare
hippocampus
septal nuclei + nu. accumbens
diagonal band (Foville)(external aspect of part of the ventral
amygdalofugal pathway)(part of extended amygdala)
8 inferior thalamic pedicle
9 lateral olfactory stria
10 fasciculus uncinatus (to orbital and medial prefrontal cortex)
11 tuberculum olfactorium
12 commissura anterior
13 medial forebrain bundle
14 amygdalo-neocortical connections
9
12
11
7
C
VA
13
Me
BL
Ce
1
8
gyrus semilunaris
of the uncus
ST
2
VA ventral amygdalofugal pathway
ST stria terminalis
FU fasciculus uncinatus
M foramen of Monro
Me medial nucleus
C cortical nucleus (olfactory)
Ce central nucleus (hypothalamus and stem)
BL basolateral complex (temporal and frontal cortex) B + L + AB
AB
adpated from
Nieuwenhuys et al.1988
amygdala and neocortical targets
orbital and medial prefrontal ACC (anterior cingulate
cortex
cortex)
FU
mediodorsal and other
thalamic nuclei
ventral forebrain
cholinergic nuclei
VA
brainstem RF
M foramen of Monro
Me medial nucleus
C cortical nucleus (olfactory)
Ce central nucleus (hypothalamus
and stem)
BL basolateral complex (temporal
and frontal cortex) B + L + AB
ST
visceral and motor effectors
hypothalamus
FU
BL
ST
MFB
C
amygdala
C
olfactory bulb and
trigonum
neocortex: frontal,
temporal and occipital
BL
Ce
BL
Me
(para)hippocampal, cingulate
and insular cortex
ST
VA
AmCor
A
main hippocampal (HC) efferent
1 fimbria
2 crura fornicis
3 fornix
4 columna fornicis
main amygdalar (A) efferents
VA ventral amygdalofugal tract
ST stria terminalis (= dorsal amygdalofugal tract)
AmCor amygdalocortical connections
FU fasciculus uncinatus
nuclei within the amygdala (Gloor 1997)
pyramidal projection neurons (Glu)
stellate interneurons (GABA)
many peptides in neuropil
steroid receptors
amygdala
transitional zones
- amygdalo-hippocampal area
- intercalated masses
central group Ce
- most dorsal position
- not at surface
- extends in bed nucleus of stria terminalis
- main output centre via connections to
hypothalamus and brainstem
- direct afferents from outside amygdala or
serial via basolateral nuclei in the
amygdala
basolateral group BL
- cortex-like but not reaching uncal surface
- L lateral (lipofuscin+), B basal, AB accessory
basal (muscarinic receptors+) and PL
paralaminar nuclei
- covered by anterior commissure
- lateral nucleus part of roof of temporal horn
tip
- basal nucleus at amygdalo-hippocampal border,
intense NADPH-d staining
connections
with neocortex and efferent also
to striatum
extended
amygdala
bed nucleus of stria terminalis
- intra-amygdaloid, supracapsular
and paraseptal parts
- argyrophilic neurons
corticomedial group C, Me
- cortical nucleus C at surface of the
uncus in gyrus semilunaris
- medial nucleus Me
- mainly olfactory input
- rich in neurotransmitters and peptides
sublenticular former substantia innominata
- under anterior commissure
- extending from precommissural septal area
to amygdala
- ventral (basal) forebrain contains: septal
nuclei, nuclei of the diagonal band, nucleus
accumbens septi, nucleus of Meynert
(cholingeric) and sublencticular substantia
innominata
magnocellular cholinergic nuclei appear early in the
ventral forebrain, comprising septal nuclei, nucleus of
the diagonal band and basal nucleus of Meynert; the
innervation of the neocortex by these cells may
proceed from around 15w to up to around 28w PMA
amygdala and entorhinal cortex
the entorhinal cortex is a gateway for the basolateral
amygdala to change the information processed
between hippocampus and neocortex; several hours
after learning there is concerted and distributed
activity to harness memories; nucleus accumbens is a
bridge mediating influence of the amygdala on the
hippocampus
- the
BST
ant
.
Put
amygdala either modulate
or
- process simultaneously with EC and neocortex
ST
but the end result is that memories are consolidated
and invested with motivation under the influence of
the amygdala
VA
HY
Co
Ce
BL
basolateral
amygdala
hippocampus
entorhinal
cortex
adpated from ten
Donkelaar et al.2006
neocortex
nucleus accumbens
efferents of amygdala (many to hypothalamus) via
- ST stria terminalis
- VA ventral amygdalofugal pathway
SEPTUM
EX
S
RT
PU
CO
AM
C
L
A
PO
MP
HIP
CA
O
IPP
AH
PAR
AMYGDALA
PARAHIP
POCAMP
AL
CORTEX
Am
ORH
ENT
HIN
PERIR
OC
Hip
TE
TEX
COR
L
A
IN
RTEX
AL CO
monkey:
cortical processing of visual information from the
striate cortex (OC) to the inferotemporal cortex (TE)
area TE projects to the amygdala (Am) and to the
hippocampus (Hip) via the parahippocampal gyrus
and perirhinal cortex
sections of the basal forebrain in relation to the amygdala
Cd
BST
S
ac
Db
GPe
VS
GPi
BM
Cd
Th
BST
Put
f
ac
M
Ce
M
Ce
BL
BL
series of frontal sections through the human basal forebrain, from rostral to caudal; the large dots indicate the large,
cholinergic cells of the basal nucleus of Meynert (BM)
ac anterior commissure, BL basolateral amygdala, BST bed nucleus of the stria terminalis, Cd caudate nucleus, Ce central
amygdala, cho chiasma opticum, Cl claustrum, Db diagonal band of Broca, f fornix, GP globus pallidus, GPe GPi external and
internal parts of globus pallidus, Hip hippocampus, In insula, M medial amygdala, ot optic tract, Put putamen, S septum, Th
thalamus, VP ventral pallidum, VS ventral striatum
(ten Donkelaar et al. 2006)
fetal development of the amygdala
9w PMA
26w PMA
4
1
2
1
2
3
4
3
cortical
basolateral and central
anterior
medial
fetal development of the amygdala (Mulc et al. 2024)
early fetal
9-13w PMA
cell mass in BL and Ce, cell
layer in CM
mainly progenitor cells -> proliferation
no fibers
and migration
midfetal
14-24w PMA
all nuclei present and septa
appearing
emerging calretinin + interneurons ->
synaptogenesis and interneuron
migration
fibers in
dorsal areas
late fetal
25-34w PMA
mature division, septa
disappearing
adultlike neurons mixed with
progenitor cells -> widespread
synaptogenesis and fiber formation
fibers amidst
nuclei
neonate
35-38w PMA
adult shape, glial migratory
streams disappearing
mature cell skeleton
onset of
myelination
-
there is a superficial and deep part to the amygdala
-
the deep part comprises the lateral, basolateral, medial and paralaminar nuclei
-
amygadaloid cells derive from the MVE via a lateral and medial (to the striatum) migratory stream
-
neurogenesis in humans spans from PMA week 7 to 12 (GA w 5 to 10), the amygdalo-hippocampal
area, intercalated masses and bed nucleus of the stria terminalis being latest to divide and migrate;
medial and cortical nuclei appear slightly before basolateral nuclei
location of the amygdala
15
4
11
14
7
7
10
16
5
6
6
8
11
2
15
3
9
1
2
4
12
Co
Ce
13
Co
16
10
1
BL
adpated from Altman &
Bayer 2015
1 Amygdala: BL (basolateral complex), Ce
(central nucleus), Co (corticomedial
complex)
2 anterior commissure
3 basal nucleus of Meynert
4 fornix
5 ventral striatum
6 globus pallidus
7 putamen
8 zona incerta Forel
9 medial forebrain bundle
10 fasciculus uncinatus
11 stria terminalis
12 optic tract
13 hypothalamus
14 thalamus
15 STF 1-6
16 lateral migratory stream
amygdalar nuclei fetus to adult
Ce
claustrum
Me
optic
tract
C
AB
amygdalohippocampal
transition
lateral
medial
B
L
PL
entorhinal
cortex
adult Gloor 1997
olfactory
tubercle
lateral
lateral olfactory
tract
medial
amygdala
hippocampus
mesencephalon
preterm 23w PMA Altman & Bayer 2015
migration tracts for the amygdala
EC
MMS
ST
IC
BNS
P
pall.
AC
DB
Cl
AChE (acetylcholinesterase) fiber system that partitions the ventral striatum into “terminal islands” (Paxinos and Mai 2004)
amygdaloid nuclei are the result of migration along the
LMS and MMS, with different progenitor sources
lateral stream LMS: from corticostriatal sulcus, along
lateral putamen in external capsule, to amgydaloid
complex
medial stream MMS: to ventral forebrain and amygdala;
originates in MVE (medial ventricular eminence)
AC anterior commissure
ANC amygdaloid nuclear complex
BNS bed nucleus of the stria terminalis
Cl claustrum
DB diagonal band
EC external capsule
IC internal capsule
P putamen
ST stria terminalis
T thalamus
terminal islands
1 nucleus accumbens lateral
2 stream to BNS
3 nucleus accumbens medial
4 tuber olfactorius
5 great terminal island of Calleja
amygdala in parasagittal CUS
putamen
pallidum
thalamus
uncus
issure
erse f
transv
sulcus rhinalis
substantia
innominata
lateral geniculate
Uncus
amygdala in behaviour
primary amygdalar nuclei and basic circuit
connections and function are conserved
across species (from the brains of a lizard,
mouse, rat, cat, monkey and human
Janak and Tye 2015