Nature Communications,
Год журнала:
2018,
Номер
9(1)
Опубликована: Янв. 9, 2018
Addiction
involves
a
predominance
of
habitual
control
mediated
through
action
selection
processes
in
dorsal
striatum.
Research
has
largely
focused
on
neural
mechanisms
mediating
proposed
progression
from
ventral
to
lateral
striatal
addiction.
However,
over
reliance
habit
may
also
arise
reduced
cortical
input
striatum,
thereby
disrupting
executive
selection.
Here,
we
identify
novel
which
chronic
intermittent
ethanol
exposure
and
withdrawal
(CIE)
disrupts
top-down
goal-directed
produce
habits.
We
find
CIE
results
decreased
excitability
orbital
frontal
cortex
(OFC)
excitatory
circuits
supporting
control,
and,
strikingly,
selectively
reduces
OFC
output
the
direct
pathway
medial
Increasing
activity
restores
CIE-exposed
mice.
Our
findings
show
alcohol
dependence
can
disrupted
communication
between
top-down,
onto
basal
ganglia
pathways
controlling
Trends in Neurosciences,
Год журнала:
2019,
Номер
42(3), С. 205 - 220
Опубликована: Янв. 6, 2019
The
mesolimbic
hypothesis
has
been
a
central
dogma
of
schizophrenia
for
decades,
positing
that
aberrant
functioning
midbrain
dopamine
projections
to
limbic
regions
causes
psychotic
symptoms.
Recently,
however,
advances
in
neuroimaging
techniques
have
led
the
unanticipated
finding
dopaminergic
dysfunction
is
greatest
within
nigrostriatal
pathways,
implicating
dorsal
striatum
pathophysiology
and
calling
into
question
theory.
At
same
time
our
knowledge
striatal
anatomy
function
progressed,
suggesting
new
mechanisms
via
which
may
contribute
symptoms
schizophrenia.
This
Review
draws
together
these
developments,
explore
what
they
mean
understanding
pathophysiology,
clinical
manifestations,
treatment
disorder.
Annual Review of Neuroscience,
Год журнала:
2019,
Номер
42(1), С. 459 - 483
Опубликована: Апрель 24, 2019
Deciding
what
to
do
and
when
move
is
vital
our
survival.
Clinical
fundamental
studies
have
identified
basal
ganglia
circuits
as
critical
for
this
process.
The
main
input
nucleus
of
the
ganglia,
striatum,
receives
inputs
from
frontal,
sensory,
motor
cortices
interconnected
thalamic
areas
that
provide
information
about
potential
goals,
context,
actions
directly
or
indirectly
modulates
outputs.
striatum
also
dopaminergic
can
signal
reward
prediction
errors
behavioral
transitions
movement
initiation.
Here
we
review
models
how
direct
indirect
pathways
modulate
outputs
facilitate
initiation,
discuss
role
cortical
in
determining
if
it.
Complex
but
exciting
scenarios
emerge
shed
new
light
on
self-paced
The
insular
cortex
(IC)
plays
key
roles
in
emotional
and
regulatory
brain
functions
is
affected
across
psychiatric
diseases.
However,
the
brain-wide
connections
of
mouse
IC
have
not
been
comprehensively
mapped.
Here,
we
traced
whole-brain
inputs
outputs
its
rostro-caudal
extent.
We
employed
cell-type-specific
monosynaptic
rabies
virus
tracings
to
characterize
afferent
onto
either
excitatory
or
inhibitory
neurons,
adeno-associated
viral
label
efferent
axons.
While
connectivity
between
other
cortical
regions
was
highly
bidirectional,
with
subcortical
structures
often
unidirectional,
revealing
prominent
cortical-to-subcortical
subcortical-to-cortical
pathways.
posterior
medial
exhibited
resembling
patterns,
while
anterior
distinct,
suggesting
two
major
functional
compartments.
Our
results
provide
insights
into
anatomical
architecture
thus
a
structural
basis
guide
investigations
complex
functions.
How
to
model
hallucinations
in
mice
There
has
not
been
enough
progress
our
understanding
of
the
basic
mechanisms
underlying
psychosis.
Studying
psychotic
disorders
animal
models
is
difficult
because
diagnosis
relies
on
self-reported
symptoms
that
can
only
be
assessed
humans.
Schmack
et
al.
developed
a
paradigm
probe
and
rigorously
measure
experimentally
controlled
rodents
(see
Perspective
by
Matamales).
Using
dopamine-sensor
measurements
circuit
pharmacological
manipulations,
they
demonstrated
brain
link
between
excessive
dopamine
hallucination-like
experience.
This
could
potentially
useful
as
translational
common
described
various
psychiatric
disorders.
It
may
also
help
development
new
therapeutic
approaches
based
anatomically
selective
modulation
function.
Science
,
this
issue
p.
eabf4740
;
see
33
Frontiers in Pharmacology,
Год журнала:
2020,
Номер
11
Опубликована: Июль 14, 2020
Dopamine
receptors
are
widely
distributed
within
the
brain
where
they
play
critical
modulatory
roles
on
motor
functions,
motivation
and
drive,
as
well
cognition.
The
identification
of
5
genes
coding
for
different
dopamine
receptor
subtypes,
pharmacologically
grouped
D1-
(D1
&
D5)
or
D2-like
(D2S,
D2L,
D3
D4)
has
allowed
demonstration
differential
distribution
in
structures,
this
being
likely
associated
to
functional
differences.
Recent
advances
function
still
point
at
most
relevant
therapeutic
target
schizophrenia
development
antipsychotics.
concentrated
caudate
putamen
with
moderate
densities
throughout
cortical
structures.
Progress
chemistry
ligands-antagonists
-partial
agonists
have
provided
more
selective
compounds
possibly
study
specific
physiological
these
subtypes
relation
symptoms.
Moreover,
an
extensive
evaluation
effect
agents
coupling
intracellular
signaling
highlights
important
differences
that
could
also
result
highly
differentiated
clinical
pharmacology.
review
summarizes
recent
field
addressing
relevance
emerging
new
targets
research
neurocircuitry.
