Required reading:

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Structure and function of the thalamic system
Required reading Steriade M, McCormick DA,
Sejnowski TJ. Thalamocortical oscillations in the
sleeping and aroused brain.Science. 1993,
262679-685.
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Thalamic nuclei (left)
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Connections and functions of thalamic nuclei
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human
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FIRST ORDER NUCLEI
HIGHER ORDER NUCLEI
Ctx. Layer V
Ctx. Layer VI
Reticular n.
Thal.
ZI
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FIRST ORDER NUCLEI
HIGHER ORDER NUCLEI
Neocortex
Rt.
Thal.
ZI/APT
Brainstem
Sensory afferents
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Primary relay nuclei.Feedback inhibition from
RT. Faithful transmission of peripheral
information to neocortex . Feed-back from layer
VI cortical neurons. Primary sensory nuclei, the
anterior nuclear group and the motor nuclei
(calbindin-negative relay cells). Main GABAergic
innervation intrinsic nucleus reticularis
thalami (RT dendro-dendritic contacts between RT
cells sparse recurrent collaterals) Topographical
relationship among thalamo-cortical,
cortico-thalamic neurons and RT neurons eg.
Cortical barrels and thalamic
barreloids Higher order thalamic nuclei Large
proportion of the GABAergic afferents to higher
order nuclei has extrareticular origin more
complex functions, including attention,
perception and memory formation. May use
different coding strategies, have different
receptive field properties and are more dependent
on the activity of neocortex than primary relay
nuclei. Prominent excitatory input from cortical
layer V. e. g, mediodorsal nucleus and the
intralaminar nuclei (immunoreactive for
calbindin). Main GABAergic innervation zona
incerta (ZI), anterior pretectal nucleus (APT)
Activity of ZI/APT is independent of the
immediate response of thalamic relay cells (no
feed-back)
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Firing patterns of thalamic neurons depend on
polarization level
Jansen, Llinas, 1984
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Firing patterns of thalamic neurons depend on
polarization level
Llinas,Jansen, 1982
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The EEG during sleep and waking During the
waking state, the EEG is characterized by low
voltage, higher frequencies (gt 30 Hz). As the
person or animal goes into deeper and deeper
sleep, slow waves become more prominent. Two
particularly prevalent slow waves are delta waves
and spindle waves. Delta waves are 0.5 to 4 Hz
oscillations that are particularly prominent
during deep sleep (stages 3 and 4).
Spindle waves are 1-3 second duration epochs of
"waxing" and "waning" 6-15 Hz oscillations. The
occurrence of both delta waves and spindle waves
are indicative of synchronized oscillations in
thalamocortical systems.
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Thalamic contribution to neocortical
spindles Intracellular recordings from
reticular, thalamocortical and pyramidal tract
neurons in vivo during cortical spindle events.
Note depolarization and fast discharge of
reticular neuron and hyperpolarization and low
threshold calcium spikes (red arrows) and sodium
spikes (blue arrows) in thalamocortical neurons.
Steriade, Deschenes, 1998
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PGN neurons inhibit one and another through
GABA-A receptors (A) Intracellular recordings
in PGN neurons during the generation of spindle
waves reveal that these cells not only are
excited by thalamocortical neurons, but also
inhibited by other PGN cells. Thus, barrages
of postsynaptic potentials are often dominated
by EPSPs initially (from the burst firing
of thalamocortical cells) that give way to IPSPs
(from the burst firing of neighboring PGN cells).
(B) The activation of PGN cells with local
application of glutamate results in the
generation of IPSPs in another PGN cell. Changing
the timing of this IPSP in relation to the
generation of a rebound low threshold Ca2 spike
reveals that PGN to PGN inhibition can have a
potent inhibitory effect on these Ca2 spikes.
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Thalamic mechanisms of sleep spindles
Steriade, McCormick, Sejnowski. 1993
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How is it that the synchronized oscillations of
sleep disappear in the transition to the waking
state and what neurotransmitters mediate this?
ACh and NE depolarize thalamocortical
neurons. The application of ACh or NE results in
the depolarization of thalamocortical neurons
through the reduction of a "leak" potassium
current. This depolarization results in the
abolition of low threshold Ca2 spikes and, if
large enough, the occurrence of single spike
activity.
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The activation of many different receptors
subtypes is capable of abolishing the generation
of spindle waves and promoting the generation of
single spike activity. This transition is similar
to that associated with moving from slow
wave sleep to waking or REM sleep. In
thalamocortical relay cells the activation of
muscarinic, alpha-1 adrenergic, H1-histaminergic,
or glutamate metabotropic receptors results in
the reduction of a leak potassium current and the
depolarization of the cell. In addition, the
activation of beta-adrenergic, serotoninergic,
and H2-histaminergic receptors results in the
abolition of spindle waves through the
enhancement of the H-current. In Perigeniculate
neurons, the activation of alpha1-adrenoceptors,
serotoninergic-2 (or 1C) receptors, or
glutamate metabotropic receptors results in the
depolarization of these cells and a block of
spindle wave generation.
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Kandel, Buzsaki, 1997
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Thalamic hypothesis of spike-and-wave
(generalized) epilepsy Enhanced GABAB-receptor
mediated IPSPs in thalamocortical neurons
Von Krosigk, Bal, McCormick, Science, 1993
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Von Krosigk, Bal, McCormick, Science, 1993
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The normal generation of spindle waves involves a
cyclical interaction between thalamocortical
relay cells and the GABAergic neurons of the
perigeniculate nucleus. PGN neurons burst and
inhibit thalamocortical cells. Some of
these rebound burst and re-excite the PGN cells.
The generalization of this activity throughout
the network results in propagation of the
oscillation and the "waxing" of the spindle wave
in the EEG. Normally, PGN cells inhibit one
and another and therefore regulate the amplitude
of each burst of action potentials during spindle
wave generation. The block of GABA-A receptors
with bicuculline results in removal of the PGN to
PGN cell inhibition. This results in a greatly
enhanced duration and amplitude of action
potential bursts in PGN cells. The enhanced
release of GABA is proposed to result in strong
activation of GABA-B receptors on thalamocortical
neurons. This results in a slow, long duration
IPSP in thalamocortical cells that is
particularly effective in activating large
rebound low threshold Ca2 spikes. The subsequent
strong bursts of action potentials in
thalamocortical cells excites PGN neurons even
more, resulting in a positive feedback loop and
the generation of seizures.
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Increased cortical excitability can convert sleep
spindles into spike-and-wave pattern