MKP THALAMUS - keywords
the diencephalic neuromere at the end of the embryonic period
human 9 wks PMA
1
2
3
4
5
6
7
neocortex
striatum
pallidum
preoptic area
septal roofplate
anterior commissure
zli zona limitans
intrathalamica (in sulcus
limitans anterior)
8 eye
9 peduncular hypothalamus
10 terminal hypothalamus
human 8 wks PMA
1
pallium
11
12
13
14
15
16
17
18
19
20
21
22
subthalamus
mammillary body
substantia nigra
midbrain
rhombomeres
isthmus
cerebellum
cephalic flexure
cervical flexure
pituitary gland
roofplate
pineal gland
22
21
thalamus
internal capsule
P2
14
P1
sulcus limitans
pre/subthalamus
7
2
subpallium
17
18
P3
3
16
13
15
11
12
9
5
19
6
4
10
8
thalamus
pre/subthalamus
hypothalamus
from Altman and Bayer 2015
20
caudal diencephalon =
P1 = pretectum
P2 = thalamus (dorsalis) + habenula
P3 = thalamus ventralis or prethalamus =
subthalamus + nu. reticularis + zona
incerta + nu. pregeniculatus
rostral diencephalon = hypothalamus
secondary organizers
1 hem (mesial) and anti-hem (lateral convexity)
2 anterior neural ridge
3 zona limitans intrathalamica
4 roofplate organizer
5 isthmic organizer
6 floorplate organizer
4
1
1
adapted from Puelles et al. 2013
3
2
5
6
early nuclear separation in thalamus
human 11 wks PMA
timespan of diencephalic thalamic neurogenesis
human weeks PMA
7
8
9
10
11
12
lateral geniculate
medial geniculate
ventrobasal
reticular
11 wks
anterior
mediodorsal
paraventricular
parafascicular (posterior
intralaminar)
from Altman and Bayer 2015
1 medial ganglionic eminence
2 lateral ganglionic eminence
3 caudal part of ganglionic eminence
4 internal capsule
5 putamen
6 medial amygdaloid nucleus
7 basal amygdaloid nucleus
8 septum
9 accumbens nucleus
10 nucleus of diagonal band
11 hippocampal formation
12 neopallium
13 cortical plate
14 Oolfactory tubercle
15 choroid plexus
16 habenular ganglion
17
18
19
20
21
22
23
24
25
26
27
28
dorsal thalamus
dorsal lateral geniculate nucleus
zona limitans intrathalamica
ventral thalamus (zona incerta and
reticular nucleus)
ventral lateral geniculate nucleus
subthalamic nucleus
hypothalamus
mamillary body
piriform cortex
ventral pallium (claustral stream)
pallio-subpallial boundary
pallidum
adapted from Nieuwenhuys et al. 2008
sources of cortical and thalamic GABAergic neurons in man
sources for interneurons with tangential migration
5
1 anterior pathway from caudal ganglionic eminence in the temporal
area (CGE) (25 %)(reelin and vaso-active intestinal peptide + cells)
5
(genes: Sp8, Prox1)
2 medial ganglionic eminence (MGE) to frontal cortex: rostral
migratory stream (65 %)(parvalbumin and somatostatin + cells)
3
(genes: Nkx2-1, Lhx6, Sox 6, SatB1)
2
- from preoptic area (10 %)
1
4
cortical interneuron generation with radial glial migration
3 medial migratory stream (septal area) to ventromedial prefrontal cortex
4 rostral migratory stream to olfactory bulb
5 a postnatal (first five months) stream of GABA-ergic neurons leaves an
Arc of subventricular proliferation areas along the lateral ventricles
1 caudal telencephalic ganglionic eminence (CGT)
2 medial telencephalic ganglionic eminence
3 septal neuroepithelium
4 olfactory neuroepithelium
5 Arc of periventricular progenitors for late GABAergic migration
1
2
3
4
5
6
7
third ventricle diencephalic neuroepithelium
telencephalic ganglionic eminence
corpus gangliothalamicum
centromedian thalamic nucleus
pallidum
internal capsule
third ventricle
10w GA: diencephalic
24w GA: telencephalic
-
early diencephalic neurogeneration
-
later telencephalic neurogeneration
- transient, human-specific structure
- tangential migration from telencephalic CGE via
corpus gangliothalamicum (CGT) to thalamic
pulvinar (P) and mediodorsal nucleus (MD)
2
3
4
1
6
5
7
after Rakić and Sidman 1969
growth trajectory of thalamic axons into the subplate
human 16 wks PMA
human 21 wks PMA
progression of thalamo-cortical axons
CP
23w
19w
sSP
a associative fibers preterm and near term)
b basal forebrain fibers (AChE +)(from 10w PMA on)
c thalamo-cortical fibers (AChE +)(from 10 wPMA on)
(cause delamination of SVZ into OSVZ and ISVZ, forming a
MACC)
d commissural (callosal) fibers (from 17 w PMA on)
a-d = MACC (MACC multilaminar axonal-cellular compartment)
14w
dSP
V
IZ
MACC
10w
PSB
c
fornix
a
DTB
b
ESS
IV
d
III
V
ISS
SS
VZ
V Z -S
I
II
thalamus
EC
hypothalamus
DTB di-telencephalic border
PSB pallial-subpallial boundary
IZ intermediate zone
dSP deep subplate
sSP superficial subplate
CP cortical plate
adapted from Altman and Bayer 2015
white matter segments (chronological appearance)
I periventricular fiber rich zone
II SS stratum sagittale (internal ISS and external ESS)
III CSO centrum semi-ovale
IV gyral core
V intracortical
subplate function in early neocortical development
subplate afferents
marginal zone
cortical plate
SPN sources
SPN
subplate
SPN
ventricular zone
rostromedial telencephalic wall
medial ganglionic eminence
thalamus
glu
GABA
sequential developmental phases in spontaneous activity:
subplate efferents
Cajal-Retzius neuron
marginal zone
cortical plate
linking
thalamocortical to
corticothalamic
networks
thalamus
subplate
(1)Cajal-Retzius and subplate neuronal activity: isolated
and asynchronous
(2)local synchronized activity in small networks or
propagating activity waves
(3)synchronized bursts with delta-activity (spindle bursts)
or gamma-bursts; cortical oscillations (in specific
circuits) and giant depolarising potentials
(4)desynchronized activity due to progressively stronger
impact of peripheral sensory input.
corpus
callosum
thalamic nuclei are organised by afferent subcortical axons in the critical period
monkey fetus
day 87
day 144
day 124
dorsal lateral
geniculate
~human 30w PMA
overlap
segregation
monkey: thalamo-cortical afferents from LG
segregated, early cortical column formation
visual cortical
area 17
cortical
layers
cortical plate
ventricular zone
magnocellular
parvocellular
koinocellular
SP = subplate
● axons from contralateral eye CO (injected)
○ axons from ipsilateral eye IP ( not injected)
in the mature monkey
- early generated neurons lie in ventral magnocellular layers, neurons generated later in dorsal parvocellular layers
- the same proliferative unit eventually establishes a single “projection column”
adapted from Rakic 1977
different retinal cells retain different
synapse locations in the cortex
thalamic regions and their cortical projections (functional loops)
tasks of thalamus
- build a sensory picture of the world
fornix
- constant update (control) of motor
commands issued from sensory input
PMA
choroid
plexus
5
MI
SI
4
1
A
limbic
3
2
FEF
motor
SSC
3
1
M
L
7
prefrontal
sensory
C
arousal
4
P
visual attention
LG
SMA
MG
auditory
visual
1
3
4
5
trigonum habenulare
1 prefrontal loop: mediodorsal and ventral anterior thalamus -> dorsolateral prefrontal
cortex (reciprocal via caudate head, pallidum, substantia nigra pr)
2 oculomotor loop: mediodorsal and ventral anterior thalamus -> frontal eye field FEF
(reciprocal control via caudate body, pallidum, substantia nigra pr)
3 body movement loop: ventral lateral and ventral anterior thalamus -> primary motor
cortex MI, PMA and SMA (reciprocal control via putamen and pallidum)
4 sensory loop: ventral posterior thalamus -> primary sensory cortex SI
-> secondary somatosensory cortex SSC-> amygdala and hippocampus
-> parietal cortex -> PMA and SMA motor cortex
5 limbic loop: mediodorsal thalamus -> anterior gyrus cinguli and orbitofrontal cortex
6 optic loop via lateral geniculate LG
7 auditory loop via medial geniculate MG
6
Superior Region (anterior group nuclei)
anteroprincipal nucleus
1=10
CM cent
Intralamin
Hb habe
ILALD
anteri
later
CeMe
LGNcent
late
limita
CL Li
central
later
CucLPcucull
ventrolateral (sensorimotor) thalamus
AV anteroventral nucleus
AM anteromedial nucleus
AD anterodorsal nucleus
thalamic nuclei
DSf dorsal superficial nucleus
ATR
3=12—————————————
A anterior
IL intralaminar
LG lateral geniculate
11
LP lateral posterior
MD mediodorsal
MDMC magnocellular mediodorsal nucleus, (medial
MD; Ncl.
PULV pulvinar
medialis
FPTfibrosus)
VA ventral
anterior
MDPC parvicellular mediodorsal nucleus, (central
MD; Ncl.
VL ventrolateral
medialis fasciculosus)
VP ventral posterior
MDPL paralaminar (paralamellar) mediodorsal nucleus,
(lateral MD; Ncl. densocellularis / multiformis)
ATR anterior thalamic radiation
AR acoustic radiation
Lateral Region
CBT corticobulbar tract
Motor Thalamus
CST corticospinal tract
pallidum
LV lateral ventricle
5
VA ventral anterior nucleus
OPT occipitopontine tract
VAM medial (nigral afferents) VAMC magnocellular
OR optic radiation
ventroanterior nucleus
PPT parietopontine tract
CBT
A
VAL lateral (pallidal afferents)
PTR posterior thalamic radiation
VA
VAb basal [VM]
STR superior thalamic radiation
STR
(entry zone of nigral and amygdaloid afferents)
TPT temporopontine tract
v3 third ventricle
LV
VL
VA, VLa pallido-nigral relay
Medial Region
caudate
MD mediodorsal nucleus
putamen
2=9
VL ventrolateral
nucleus
VL
ventrolateral nucleus (oral division) VO
VLP posterior ventrolateral
MD nucleus (lateral caudal
division) Vim
CST VLA anterior
AR
PPT
LG
TPT
OPT
PTR
VP
VLPI posterior
ventrolateral nucleus, internal part
VLPE posterior ventrolateral nucleus, external part
VLb basal (inferior)IL
ventrolateral nucleus [VPI]
LP
(entry zone of the cerebellar fibers)
v3
cingular
cortex
frontal
cortex
Sensory Thalamus
PULV
VP ventroposterior
nucleus or complex, VPO and VPC
VPL lateral ventroposterior nucleus;
6
VPM medial ventroposterior nucleus
4
VPS superior ventroposterior nucleus (Kaas)
VPPC ventroposterior nucleus, parvicellular part VPMPC
medial ventroposterior nucleus, parvicellular part
VPb basal ventroposterior nucleus [VMpo]
MV med
Periventri
Pf paraf
Po poste
dorsal
com
ant
PT PuA
paraten
infe
PV PuI
parave
VLP cerebellar motor input
VP sensory relay
VP
PuL late
VL
VA
PuM me
ventral
co
Pv parav
formation
reticu
A Re Rreunien
Sg supra
SM SN
submed
subst
sPf subp
Posterior
STh sub
anterolateral
PulVA
pulvin
ventr
3,6 mm dorsal to intercommissural plane
adapted from Percheron 2004
APul
anter
VAmc
ve
VLa ante
ven
ADPul
VLp venn
posterior
zona incerta
ven
central groove
IPulVLpl
inferio
VLpd
ve
IDPul
infer
frontal and preSMA accessory
premotor motor cortex,
somatosensory somatosensory
VLpv
ve
ILPul
infer
cortex,
supplementary
motor area
cortex
MI,4
cortex, deep
VM vent
infer
cutaneus SI,3b IVPul
eye field
and SMA
3a
VPI vent
IGPul inter
and 1
VPL ven
LPul
latera
VPLa ve
MPul
medi
VPLp
ve
MLPul
VPMmed
ven
SFPul
supev
VPMpc
SPul super
1,8 mm ventral to intercommissural plane
VA
VO
VImM
VImL
VPO
VPC
(entry zone of sensory afferents)
LV
tectum
OR
adapted from Nieuwenhuys et al. 2008
MB mam
med
ILCMD
centra
VACMMDmc
centrom
MDpc m
VP
PF
parafas
PULV
MDpl me
SPf subpar
MGN me
ILPMGm
posteri
me
nucleus
MGv
me
11,3 mm dorsal to intercommissural plane
posterolateral
SGeMTT
suprag
ma
from substantia
nigra, tectum and
amygdala
from pallidum
internum and
pedunculopontine
nucleus
Epithalam
HB habenu
HBL latera
HBM media
spinothalamic
tracts
from cerebellar
nuclei, vestibular
nuclei and
spinothalamic
tracts
from kinaesthetic
lemniscus medialis
information
Prethalam
PRt preret
Fa fascicu
from cutaneous
lemniscus medialis
information
Metathala
LG lateral
MG medial
function of thalamus: nuclei with drivers and modulators
a thalamic triad (glomerulus) in a subcortical relay
thalamic connections
I ionotropic receptor
non-neocortical
cortico-thalamic
connections are bilateral
neocortical
M metabotropic receptor
F terminal: flattened vesicle (F1 axonal, F2 dendritic)
RL terminal: round vesicle and large profiles
RS terminal: round vesicle and small profiles
RTN
striatum
thalamo -> cortical
connections are strictly
unilateral
5
3
F1
M
I
allocortex
4
I
M
amygdala
RS
4
2
RL
massive connections from cortex to RTN
I
I
3
1
no connections RTN to cortex
first order
thalamic drivers
VA, VL, VP
LG
MG
higher order
reciprocal
A, MD,
IL, P
1 excitatory driver (GLU) from sensory organ (subcortical, e.g.retina or skin
forming RL terminal) to first order or from cortical neuron in layer 5 to higher
order relay (forming RS terminal); divergence: one cortical axon innervates
several thalamic higher order neurons; axons from cortical layer 6 also
innervate first order thalamic neurons; no collaterals to TRN from first or higher
order drivers
2 relay cell dendrite : answers linearly with tonic firing to drivers, answers to
combined modulator and inhibitor influence with burst firing (rhytmic or
arrhytmic)
3 inhibitory interneuron dendrite (GABA, F2 terminal) or from thalamic reticular
neuron (GABA, F1 terminal); TRN cells only inhibit relay cells
first order drivers: retinogeniculate axons
to LG, lemniscus medialis to VP, colliculus
inferior to MG, spinothalamic tract to VP,
cerebellum to VL, mammillary bodies to A
4 excitatory modulator axon from brainstem (cholinergic plus NO for
parabrachial nuclei, NOR for locus ceruleus, serotonine for raphe nuclei)(RS
terminals); also from tuberomammillary nucleus in hypothalamus (histamine)
and from basal forebrain to TRN (cholinergic); in addition modulator input from
basal ganglia to ventral anterior and ventral lateral thalamus (GABA)
subcortical afferents
are uni- or bilateral
5 astrocytic sheets
neonatal thalamic activity
glucose metabolism
GABA receptor activation
preterm PMA 34w
term newborn
preterm PMA 35w
3m infant
child 2y old
parietal cortex (PC)
cingulate gyrus (Cg)
auditory cortex (AC)
basal ganglia (BG)
dentate nucleus (DN)
thalamus (Th)
brain stem (BS)
amygdala/hippocampus (Amg/ Hip)
cerebellar vermis (CV)
young adult
from Chugani 2018
arterial perfusion and venous drainage of thalamus
anterior
ICV
1 internal carotid artery
BVR
2 posterior communicating artery
b
a
3 basilar artery
a
anterior
posterior
d
lateral
b
c
c
PCoA
BVR
PCoA
PCA
PCA
d
4 tuberothalamic artery (polar a.): to anteromedial and
ICV
anterolateral thalamus including mammillothalamic
medial
tract, TRN
5 paramedian pedicle (thalamic perforator aa.): to
posteromedial thalamus and subthalamus
6 thalamogeniculate aa.: to ventrolateral thalamus, lateral
CM
7 posterior choroidal a. : to posterior (pulvinar and
posterior
geniculates) and anteromedial thalamus (part of ANT)
8 posterior cerebral artery
ICV internal cerebral vein
BVR basal vein of Rosenthal
a anterior, b superior, c inferior and d posterior thalamic
veins
CL, CM central lateral and centromedian nuclei
Co commissural nucleus
mtt mammillothalamic tract
Pula, Pull, Pulm anterior, lateral and medial nuclei of pulvinar
R reticular nucleus
VA ventral anterior nucleus
VLa, VLp anterior and posterior parts of ventral lateral nucleus
VPM ventroposterior medial nucleus
after ten Donkelaar 2011
and Barth et al. 1995
VPLa, VPLp anterior and posterior parts of ventroposterior
lateral nucleus
doppler images of PCoA and PCA perforators to thalamus
anterior coronal
posterior coronal
ICV
ICV
tuberothalamic a.
P2 PCA medial posterior choroidal a.
P1 PCA perforator a.
P2 PCA thalamogeniculate aa.
parasagittal
P1 PCA perforator a.
P2 PCA thalamogeniculate aa.
arterial thalamic stroke types
tuberothalamic
(polar) a.
MCA
AChA
PCA
thalamogeniculate a.
ICA
lateral posterior
choroidal a.
PCoA
PCA P1
perforator a.
basilar a.
left thalamogeniculate PCA stroke
term, neonatal seizures day 2, no risk factors except IVF
lesions in the anterior region
parechovirus
encephalitis
day 33
day 38 day 24
day 33
MRI day 5
PRES
DWI negative
CUS day 5
courtesy S Horsch, Berlin
vasogenic oedema, mainly in striatum
anterior region
choroidal AVM
lesions in the mediodorsal region
ICV tributary
thrombosis
P1 PCA
perforator
stroke
mediodorsal region
thalamic DVA
lesions in the ventral anterior region
1
ventral anterior and
ventral lateral region
chance finding, infant with minor
trauma; transient imaging findings,
without residual dysfunction
(courtesy S Horsch, Berlin)
2
centre médian, central
region
ventral anterior region
3
mediodorsal nucleus
lesions in the ventral lateral and ventral posterior region (1)
intrapartum asphyxia:
term, day 12, fetal
distress, caesarean,
brainstem dysfunction
MR day 4
antenatal asphyxia:
primary injury to
thalamus on day 1
ventral lateral and
ventral posterior region
postnatal hypoxia/
ischaemia: volvulus in
ELBW infant on day 42,
scans 3 weeks later
day 62 = 35w PMA
lesions in the ventral lateral and ventral posterior region (2)
primary hyperoxaluria
at 1 month
late neonatal
herpes simplex
virus encephalitis
ventral lateral and
ventral posterior region
lesions in the posterior region
34w subcortical
white matter injury,
not cavitating
posterior region
network injury from
stroke (diffusion
changes in pulvinar and
in optic radiation)
MCA
PCA
lesions in the intralaminar region
unexplained deposits in
ELBW infants (hypothesis:
Ca-P deposits,
unpublished data)
intralaminar region
T2
isob1000
swip
lesions in the geniculate region
bacterial GBS
meningitis with
arteritis
lateral geniculate
lesions in several thalamic regions
Leigh
syndrome
haemophagocytosis <
EBV
all regions
neonatal lactic acidemia due to mitochondrial transfer RNA translation optimization 1 (MTO1) deficiency
coronal from anterior fontanel
axial from temporal fontanel
uncus
mes
colliculus
superior
subthalamus
pallidum
subthalamus
d20 diffusion MR
born at 34 weeks PMA; 1500 g at birth; persistent
hyperlactacidemia (27 to 36 mg/dL) without
subthalamic nuclei; serial scans: persistent
hyperechoic subthalamic nuclei, colliculi and globi
more obvious restriction diffusion; confirmed
mitochondrial transfer RNA translation
acidosis; infection, heart failure, and
pharmacological causes ruled out; urine analysis:
unspecific high levels of Krebs cycle metabolites;
pallidi; first day 20 MRI: mild restricted diffusion
in the subthalamic nuclei and colliculi with normal
T1- and T2-weighted images; second MRI at 42
optimization 1 (MTO1) deficiency; died at age 8
months following a metabolic decompensation
with severe lactic acidosis
normal CUS on admission; second CUS at 19 days:
symmetrical increased echogenicity of the
days: clear abnormal signal intensity of these
areas on T1-and T2-weighted images as well as a
courtesy NB Carreras, Barcelona ; Aguera et al. 2022
internal cerebral vein thrombosis with thalamic haemorrhage
term, normal delivery, seizures on day 1, evolving doppler findings
day 2
day 9
day 16
high frequency probe
high frequency probe
all regions
thrombosis in ICV orr it’s
branches
arteriopathy in several thalamic regions
cerebro-retinal
genetic arteriopathy
all regions
hyperechoic signal in
thalamic perforator arteries
Aicardi-Goutières
interferonopathy
thalamic nuclei remain dependent on their cortical targets for survival
degeneration in LG following focal lesion
in cortical visual area 17 (mandrill)
sustaining collateral axonal branches: degeneration only if
all (1 + 2) major thalamo-cortical efferents disconnected
2
cortex
1
+
from Sherman and Guillery 2001
thalamic reticular nucleus
thalamus
TRN
retrograde degeneration can be due to axon destruction and
also corticothalamic (in)activity with reduced trophic support
___ branched axon from thalamus to cortex
……. other connections of importance
lesions in the posterior region and in pallidum: asphyxia or IEM ?
A
M
L
C
P
PCA P1
perforator a.
PCA posterior
lateral choroidal a.
PCA thalamogeniculate a.
more medial
more lateral
injury patterns to neonatal thalamus divided in major regions
?
PRES
frontal lobe network injury
antepartum forebrain ischaemia
EBV related immune LH destruction
A
L
M
asphyxia
hypothermia
mitochondrial
C
P
deep venous thrombosis
hyperoxaluria
bacterial meningitis
choroidal AVM
parieto-occipital network injury
HSV encephalitis
cerebro-retinal
arteriopathy (genetic)
R
Aicardi-Goutières
syndrome
arterial perforator stroke
air
deposits
inadvertent drain placement