The
posterior
dorsomedial
striatum
(pDMS)
is
necessary
for
goal-directed
action;
however,
the
role
of
direct
(dSPN)
and
indirect
(iSPN)
spiny
projection
neurons
in
pDMS
such
actions
remains
unclear.
In
this
series
experiments,
we
examined
SPNs
action
rats
found
that
whereas
dSPNs
were
critical
learning
energizing
learned
response,
iSPNs
involved
updating
to
support
response
flexibility.
Instrumental
training
elevated
expression
plasticity
marker
Zif268
only,
chemogenetic
suppression
dSPN
activity
during
prevented
learning.
Unilateral
optogenetic
inhibition
induced
an
ipsilateral
bias
performance.
contrast,
although
initial
was
unaffected
by
iSPN
manipulations,
iSPNs,
but
not
dSPNs,
impaired
attenuated
flexibility
after
changes
action-outcome
contingency.
The EMBO Journal,
Год журнала:
2024,
Номер
43(4), С. 533 - 567
Опубликована: Фев. 5, 2024
Abstract
The
phospholipid
and
free
fatty
acid
(FFA)
composition
of
neuronal
membranes
plays
a
crucial
role
in
learning
memory,
but
the
mechanisms
through
which
activity
affects
brain’s
lipid
landscape
remain
largely
unexplored.
levels
saturated
FFAs,
particularly
myristic
(C14:0),
strongly
increase
during
stimulation
memory
acquisition,
suggesting
involvement
phospholipase
A1
(PLA1)
synaptic
plasticity.
Here,
we
show
that
genetic
ablation
PLA1
isoform
DDHD2
mice
dramatically
reduces
FFA
responses
to
acquisition
across
brain.
Furthermore,
loss
also
decreases
performance
reward-based
spatial
models
prior
development
neuromuscular
deficits
mirror
human
spastic
paraplegia.
Via
pulldown-mass
spectrometry
analyses,
find
binds
key
protein
STXBP1.
Using
STXBP1/2
knockout
neurosecretory
cells
haploinsufficient
STXBP1
+/−
mouse
model
early
infantile
encephalopathy
associated
with
intellectual
disability
motor
dysfunction,
controls
targeting
plasma
membrane
generation
FFAs
These
findings
suggest
roles
for
metabolism
processes
plasticity,
learning,
memory.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Апрель 21, 2023
Abstract
Learned
associations
between
environmental
cues
and
the
outcomes
they
predict
(cue-outcome
associations)
play
a
major
role
in
behavioral
control,
guiding
not
only
which
responses
we
should
perform,
but
also
inhibit,
order
to
achieve
specific
goal.
The
encoding
of
such
cue-outcome
associations,
as
well
performance
cue-guided
choice
behavior,
is
thought
involve
dopamine
D1
D2
receptor-expressing
medium
spiny
neurons
(D1-/D2-MSNs)
nucleus
accumbens
(NAc).
Here,
using
visual
discrimination
task
male
mice,
assessed
NAc
D1-/D2-MSNs
inhibition
inappropriate
responding.
Cell-type
neuronal
silencing
in-vivo
imaging
revealed
D2-MSNs
contribute
inhibiting
responses,
with
activation
following
response
errors
playing
an
important
optimizing
future
behavior.
Our
findings
indicate
that
error-signaling
by
contributes
ability
use
inhibit
The
posterior
dorsomedial
striatum
(pDMS)
is
necessary
for
goal-directed
action;
however,
the
role
of
direct
(dSPN)
and
indirect
(iSPN)
spiny
projection
neurons
in
pDMS
such
actions
remains
unclear.
In
this
series
experiments,
we
examined
SPNs
action
rats
found
that
whereas
dSPNs
were
critical
learning
energizing
learned
response,
iSPNs
involved
updating
to
support
response
flexibility.
Instrumental
training
elevated
expression
plasticity
marker
Zif268
only,
chemogenetic
suppression
dSPN
activity
during
prevented
learning.
Unilateral
optogenetic
inhibition
induced
an
ipsilateral
bias
performance.
contrast,
although
initial
was
unaffected
by
iSPN
manipulations,
iSPNs,
but
not
dSPNs,
impaired
attenuated
flexibility
after
changes
action-outcome
contingency.
