bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Nov. 11, 2023
ABSTRACT
Here
we
describe
a
novel
group
of
basal
forebrain
(BF)
neurons
expressing
neuronal
PAS
domain
1
(Npas1),
developmental
transcription
factor
linked
to
neuropsychiatric
disorders.
Immunohistochemical
staining
in
Npas1-cre-2A-TdTomato
mice
revealed
BF
Npas1
+
are
distinct
from
well-studied
parvalbumin
or
cholinergic
neurons.
GAD67-GFP
knock-in
confirmed
that
the
vast
majority
GABAergic,
with
minimal
colocalization
glutamatergic
vGlut1-cre-tdTomato
vGlut2-cre-tdTomato
mice.
The
density
was
high,
5-6
times
neighboring
cholinergic,
Anterograde
tracing
identified
prominent
projections
brain
regions
involved
sleep-wake
control,
motivated
behaviors
and
olfaction
such
as
lateral
hypothalamus,
habenula,
nucleus
accumbens
shell,
ventral
tegmental
area
olfactory
bulb.
Chemogenetic
activation
light
(inactive)
period
increased
amount
wakefulness
latency
sleep
for
2-3
hr,
due
an
increase
long
wake
bouts
short
NREM
bouts.
Non-REM
slow-wave
(0-1.5
Hz)
sigma
(9-15
power,
well
spindle
density,
amplitude
duration,
were
reduced,
reminiscent
findings
several
Together
previous
implicating
stress
responsiveness,
anatomical
effect
activating
them
suggest
possible
role
motivationally-driven
stress-induced
insomnia.
Identification
this
major
subpopulation
GABAergic
will
facilitate
studies
their
disorders,
dementia
other
conditions
involving
BF.
SIGNIFICANCE
STATEMENT
We
characterize
mouse
subset
more
numerous
than
glutamate
target
areas
arousal,
motivation
olfaction.
Activation
slow
waves
spindles
reduced
wake-promoting
allow
insomnia,
Biology,
Journal Year:
2024,
Volume and Issue:
13(2), P. 94 - 94
Published: Feb. 2, 2024
Neural
networks
have
an
extensive
ability
to
change
in
response
environmental
stimuli.
This
flexibility
peaks
during
restricted
windows
of
time
early
life
called
critical
periods.
The
ubiquitous
occurrence
this
form
plasticity
across
sensory
modalities
and
phyla
speaks
the
importance
periods
for
proper
neural
development
function.
Extensive
investigation
into
visual
has
advanced
our
knowledge
molecular
events
key
processes
that
underlie
impact
early-life
experience
on
neuronal
plasticity.
However,
despite
olfaction
overall
survival
organism,
cellular
basis
olfactory
not
garnered
study
compared
Recent
work
providing
a
comprehensive
mapping
highly
organized
neuropil
its
turn
attracted
growing
interest
how
these
circuits
undergo
Here,
we
perform
comparative
review
fruit
flies
mice
provide
novel
insight
odor
exposure
shaping
highlighting
mechanisms
found
modalities.
Frontiers in Neural Circuits,
Journal Year:
2024,
Volume and Issue:
18
Published: Feb. 16, 2024
In
the
mouse
olfactory
system,
odor
information
is
converted
to
a
topographic
map
of
activated
glomeruli
in
bulb
(OB).
Although
arrangement
genetically
determined,
glomerular
structure
plastic
and
can
be
modified
by
environmental
stimuli.
If
pups
are
exposed
particular
odorant,
responding
become
larger
recruiting
dendrites
connecting
projection
neurons
interneurons.
This
imprinting
not
only
increases
sensitivity
odor,
but
also
imposes
positive
quality
on
imprinted
memory.
External
represented
as
an
OB
transmitted
cortex
(OC)
amygdala
for
decision
making
elicit
emotional
behavioral
outputs
using
two
distinct
neural
pathways,
innate
learned.
Innate
circuits
start
work
right
after
birth,
whereas
learned
functional
later
on.
this
paper,
recent
progress
will
summarized
study
circuit
formation
perception
mice.
We
propose
new
hypotheses
timing
gating
activity
relation
respiration
cycle.
Scientific Reports,
Journal Year:
2021,
Volume and Issue:
11(1)
Published: Nov. 4, 2021
Previous
studies
indicate
that
the
activity
of
hypothalamic
POMC
neurons
can
be
regulated
by
glucose
via
intracellular
mechanisms,
but
its
regulation
lactate
is
poorly
understood.
In
addition
to
energetic
role,
acts
as
a
signaling
molecule.
this
study,
we
evaluated
function
and
location
receptor,
hydroxycarboxylic
acid
receptor
1
(HCAR1).
We
used
conditional
genetic
approach
label
their
sensitivity
using
patch-clamp
recordings.
L-Lactate
3-chloro-5-hydroxybenzoic
(3Cl-HBA),
HCAR1
specific
agonist
depolarized
increase
in
excitability
was
abolished
pertussis
toxin
(PTX),
indicating
involvement
Gαi/o-protein-coupled
receptors.
addition,
depolarization
subset
sensitive
α-cyano-4-hydroxycinnamate
(4-CIN),
transporter
blocker,
suggesting
induced
L-lactate
also
occur
direct
action.
Surprisingly,
not
detected
neurons,
instead
localized
astrocytes.
These
results
suggest
new
lactate-mediated
mechanism
for
astrocyte-neuron
intercellular
communication.
Neurochemical Research,
Journal Year:
2024,
Volume and Issue:
49(4), P. 1008 - 1016
Published: Jan. 6, 2024
Abstract
Dysfunctional
sensory
systems,
including
altered
olfactory
function,
have
recently
been
reported
in
patients
with
autism
spectrum
disorder
(ASD).
Disturbances
processing
can
potentially
result
from
gamma-aminobutyric
acid
(GABA)ergic
synaptic
abnormalities.
The
specific
molecular
mechanism
by
which
GABAergic
transmission
affects
the
system
ASD
remains
unclear.
Therefore,
present
study
aimed
to
evaluate
selected
components
of
brain
regions
and
primary
neurons
isolated
Shank3
-deficient
(
−/−
)
mice,
are
known
for
their
autism-like
behavioral
phenotype.
deficiency
led
a
significant
reduction
GEPHYRIN/GABA
A
R
colocalization
piriform
cortex
bulb,
while
no
change
cell
morphology
was
observed.
Gene
expression
analysis
revealed
mRNA
levels
GABA
transporter
1
bulb
Collybistin
frontal
mice
compared
WT
mice.
similar
trend
observed
Somatostatin
other
neurotransmission
markers
did
not
yield
statistically
results.
Overall,
it
appears
that
leads
changes
synapses
important
information
processing,
may
represent
basis
understanding
functional
impairments
autism.
The
olfactory
bulb
(OB),
the
first
relay
for
odor
processing
in
brain,
receives
dense
GABAergic
and
cholinergic
long-range
projections
from
basal
forebrain
(BF)
nuclei
that
provide
information
about
internal
state
behavioral
context
of
animal.
However,
targets,
impact,
dynamic
these
afferents
are
still
unclear.
How
BF
synaptic
inputs
modulate
activity
diverse
subtypes
periglomerular
(PG)
interneurons
using
optogenetic
stimulation
loose
cell-attached
or
whole-cell
patch-clamp
recording
OB
slices
adult
mice
were
studied
this
article.
potently
blocked
PG
cells
firing
except
a
minority
calretinin-expressing
which
GABA
release
elicited
spiking.
Parallel
excited
previously
overlooked
cell
subtype
via
activation
M1
muscarinic
receptors.
Low-frequency
axons
drove
persistent
cells,
thereby
increasing
tonic
inhibition
principal
neurons.
Taken
together,
findings
suggest
modality-specific
can
orchestrate
glomeruli
multiple,
potentially
independent,
inhibitory
excitatory
target-specific
pathways.
Journal of Neurochemistry,
Journal Year:
2023,
Volume and Issue:
unknown
Published: Aug. 24, 2023
Abstract
Normal
brain
function
requires
a
tightly
regulated
balance
between
excitatory
and
inhibitory
neurotransmissions.
γ‐Aminobutyric
acid
type
A
(GABA
)
receptors
represent
the
major
class
of
ion
channels
in
mammalian
brain.
Dysregulation
these
and/or
their
associated
pathways
is
strongly
implicated
pathophysiology
epilepsy.
To
date,
hundreds
different
GABA
receptor
subunit
variants
have
been
with
epilepsy,
making
them
prominent
cause
genetically
linked
While
identifying
genetic
crucial
for
accurate
diagnosis
effective
counselling,
it
does
not
necessarily
lead
to
improved
personalised
treatment
options.
This
because
identification
variant
reveal
how
affected.
Genetic
subunits
can
complex
changes
properties
resulting
various
degrees
gain‐of‐function,
loss‐of‐function
or
combination
both.
Understanding
affect
therefore
represents
an
important
first
step
ongoing
development
precision
therapies.
Furthermore,
ensure
that
functional
data
are
produced
using
methodologies
allow
be
classified
clinical
guidelines
such
as
those
developed
by
American
College
Medical
Genetics
Genomics.
article
will
review
current
knowledge
field
provide
recommendations
future
analysis
variants.
image
Frontiers in Cellular Neuroscience,
Journal Year:
2021,
Volume and Issue:
15
Published: Feb. 2, 2021
Sensory
perception
underlies
how
we
internalize
and
interact
with
the
external
world.
In
order
to
adapt
changing
circumstances
interpret
signals
in
a
variety
of
contexts,
sensation
needs
be
reliable,
but
sensory
input
flexible.
An
important
mediator
this
flexibility
is
top-down
regulation
from
cholinergic
basal
forebrain.
Basal
forebrain
projection
neurons
serve
as
pacemakers
gatekeepers
for
downstream
neural
networks,
modulating
circuit
activity
across
diverse
neuronal
populations.
This
control
necessary
cue
detection,
learning,
memory,
disproportionately
disrupted
neurodegenerative
diseases
associated
cognitive
decline.
Intriguingly,
signaling
acts
locally
within
sculpt
output
neurons.
To
determine
local
impacts
pathways
that
participate
regulation,
sought
define
dynamics
during
motivated
behavior
learning.
Toward
this,
utilized
fiber
photometry
genetically
encoded
acetylcholine
indicator
GAChR2.0
temporal
patterns
olfactory-guided,
behaviors
We
show
reliably
increased
reward
seeking
behaviors,
was
strongly
suppressed
by
delivery
go/no-go
olfactory-cued
discrimination
task.
The
observed
transient
reduction
tone
mirrored
suppression
GABAergic
activity.
Together,
these
findings
suggest
changes
rapidly
reflect
reward-seeking
positive
reinforcement
may
impact
circuitry
modulates
olfaction.
Nature Communications,
Journal Year:
2022,
Volume and Issue:
13(1)
Published: Nov. 12, 2022
Abstract
In
the
olfactory
system,
cortex
sends
glutamatergic
projections
back
to
first
stage
of
processing,
bulb
(OB).
Such
corticofugal
excitatory
circuits
—
a
canonical
circuit
motif
described
in
all
sensory
systems—
dynamically
adjust
early
processing.
Here,
we
uncover
inhibitory
feedback
OB,
originating
from
subpopulation
GABAergic
neurons
anterior
and
innervating
both
local
output
OB
neurons.
vivo
imaging
network
modeling
showed
that
optogenetic
activation
cortical
drives
net
subtractive
inhibition
spontaneous
odor-evoked
activity
as
well
neurons,
stimulation
enhances
separation
population
odor
responses
tufted
cells,
but
not
mitral
cells.
Targeted
pharmacogenetic
silencing
axon
terminals
impaired
discrimination
similar
mixtures.
Thus,
represent
an
additional
control
Journal of Neurophysiology,
Journal Year:
2023,
Volume and Issue:
129(6), P. 1515 - 1533
Published: May 24, 2023
Neuronal
circuits
in
the
olfactory
bulb
closely
modulate
output
activity.
Activation
of
GABAergic
from
HDB
to
has
both
direct
and
indirect
action
differentially
across
five
classes
M/TC
bulbar
neurons.
The
net
effect
enhances
excitability
deeper
neurons
as
frequency
increases,
altering
relative
inhibition-excitation
balance
circuits.
We
hypothesize
that
this
sharpens
tuning
specificity
M/TCs
odors
during
sensory
processing.
Communications Biology,
Journal Year:
2022,
Volume and Issue:
5(1)
Published: April 6, 2022
Abstract
Corticotropin-releasing
factor
(CRF)
neurons
are
one
of
the
most
densely
distributed
cell
types
in
central
amygdala
(CeA),
and
involved
a
wide
range
behaviors
including
anxiety
learning.
However,
fundamental
input
circuits
patterns
CeA-CRF
still
unclear.
Here,
we
generate
monosynaptic-input
map
onto
at
single-cell
resolution
via
retrograde
rabies-virus
system.
We
find
all
inputs
located
44
nested
subregions
that
directly
innervate
neurons;
them
top-down
convergent
expressing
Ca
2+
/calmodulin-dependent
protein
kinase
II,
centralized
cortex,
especially
layer
4
somatosensory
which
may
relay
information
from
thalamus.
While
bottom-up
divergent
have
highest
proportion
glutamate
decarboxylase
expression.
Finally,
en
passant
structures
single
neuron
revealed
by
in-situ
reconstruction
modified
3D-reference
atlas,
represented
Periaqueductal
gray-Subparafascicular
nucleus-Subthalamic
nucleus-Globus
pallidus-Caudoputamen-CeA
pathway.
Taken
together,
our
findings
provide
morphological
connectivity
properties
neurons,
insights
for
future
studies
interrogating
circuit
mechanisms
mediating
various
functions.