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,
The Journal of Comparative Neurology,
Journal Year:
2022,
Volume and Issue:
531(3), P. 451 - 460
Published: Dec. 3, 2022
Abstract
Circuit
operations
of
the
olfactory
bulb
are
modulated
by
higher
order
projections
from
multiple
regions,
many
which
themselves
targets
bulbar
output.
Multiple
glutamatergic
regions
project
to
bulb,
including
anterior
nucleus
(AON),
prefrontal
cortex
(PFC),
piriform
(PC),
entorhinal
(EC),
and
tenia
tecta
(TT).
In
contrast,
only
one
region
provides
GABAergic
bulb.
These
GABA
neurons
located
in
horizontal
limb
diagonal
band
Broca
extending
posteriorly
through
magnocellular
preoptic
lateral
However,
it
was
unclear
whether
projecting
collaterallize
other
brain
regions.
To
address
this,
we
mapped
collateral
using
intersectional
strategies
viral
traditional
tract
tracers.
This
approach
revealed
show
remarkable
specificity
targeting
primary
cortical
exhibiting
abundant
into
accessory
AON,
PFC,
PC,
TT.
The
"nonolfactory"
receiving
sparse
connectivity
medial
orbital
cortex.
suggests
that
basal
forebrain
inhibitory
feedback
also
modulates
areas
prominent
projection
Thus,
may
be
simultaneously
modulating
both
synaptic
processing
information
associational
We
hypothesize
these
a
regulator
entire
system.
Frontiers in Psychiatry,
Journal Year:
2023,
Volume and Issue:
14
Published: March 28, 2023
People
with
schizophrenia
have
been
reported
to
show
deficits
in
tests
of
olfactory
function.
DNA
methylation
and
GABAergic
input
implicated
biochemical
processes
controlling
odor
animal
studies,
but
this
has
not
investigated
human
studies.In
a
study
measures
mRNAs
lymphocytes,
we
also
measured
identification
discrimination
the
Sniffin'
Sticks
battery
58
patients
chronic
(CSZ)
48
controls.
lymphocytes
were
assessed
by
qPCR
using
TaqManTM
probes.
Cognition
was
MATRICS
(Measurement
Treatment
Research
Improve
Schizophrenia)
CSZ
controls,
symptoms
PANSS
scale
(Positive
Negative
Symptom
Scale).
The
relationships
mRNA,
cognition,
explored
correlation
analysis.
Variables
which
significantly
differentiated
from
controls
logistic
regression.Overall,
showed
(P≤.001)
lower
scores
on
compared
moderate
effect
size,
no
difference
identification.
Deficits
discrimination,
standardly
many
prior
strongly
In
regression
analysis,
identification,
significant
variable
predicting
versus
control
class
membership.
This
is
first
report
relationship
between
blood
cells
subjects.
There
negative
correlations
enzymes
mRNAs.
Lower
associated
cognitive
CSZ,
symptom
scores,
while
higher
PANNS
Excitement
factor.Odor
more
powerful
than
discriminating
should
be
used
regularly
as
an
measure
studies
schizophrenia.
substantive
meaning
mRNA
variables
peripheral
needs
investigation
comparison
results
neural
tissue.
Frontiers in Cellular Neuroscience,
Journal Year:
2022,
Volume and Issue:
16
Published: July 27, 2022
Modulation
of
neural
circuits
is
essential
for
flexible
sensory
perception
and
decision-making
in
a
changing
environment.
Cholinergic
GABAergic
projections
to
the
olfactory
system
from
horizontal
limb
diagonal
band
Broca
(HDB)
basal
forebrain
are
crucial
odor
detection
learning.
Although
studies
have
demonstrated
that
HDB
neurons
respond
during
learning,
how
cholinergic
differ
their
response
dynamics
roles
learning
remains
unclear.
In
this
study,
we
examined
profiles
these
two
subpopulations
passive
exposure
associative
We
show
excitatory
responses
both
tended
habituate
repeated
exposure.
However,
while
habituated
were
also
observed
go-go
task,
there
was
no
such
habituation
neurons.
Moreover,
S+
S-
trials
diverged
once
mice
learned
go/no-go
task.
Furthermore,
chemogenetic
inactivation
impaired
discrimination.
Together,
findings
suggest
reflect
attention
positive
reinforcement
may
regulate
discrimination
via
top-down
inputs
system.
Journal of Neurophysiology,
Journal Year:
2024,
Volume and Issue:
131(6), P. 1226 - 1239
Published: May 1, 2024
Mitral/tufted
cells
(M/TCs)
form
complex
local
circuits
with
interneurons
in
the
olfactory
bulb
and
are
powerfully
inhibited
by
these
interneurons.
The
horizontal
limb
of
diagonal
band
Broca
(HDB),
only
GABAergic/inhibitory
source
centrifugal
circuit
bulb,
is
known
to
target
interneurons,
we
have
shown
targeting
also
glutamatergic
neurons
vitro.
However,
net
efficacy
under
different
patterns
activation
vivo
relative
balance
between
various
targeted
intact
was
focus
this
study.
Here
channelrhodopsin-2
(ChR2)
expressed
HDB
GABAergic
investigate
short-term
plasticity
HDB-activated
disinhibitory
rebound
excitation
M/TCs.
Optical
increased
spontaneous
M/TC
firing
without
odor
presentation
odor-evoked
firing.
induced
(burst
or
cluster
spiking)
all
classes
This
frequency
dependent,
facilitation
at
higher
stimulation
(5
Hz
above).
frequency-dependent
regulation
more
potent
deeper
layer
M/TCs
compared
superficial
In
neural
inhibition
plays
a
critical
functional
role,
patterned
input-dependent
inhibitory
inputs
may
help
maintain
precise
across
populations
output
environmental
odors,
putatively
sharpen
enhancement
tuning
specificity
individual
odors.
International journal of psychological research,
Journal Year:
2023,
Volume and Issue:
16(2), P. 62 - 86
Published: Aug. 23, 2023
Sensory
perception
is
one
of
the
most
fundamental
brain
functions,
allowing
individuals
to
properly
interact
and
adapt
a
constantly
changing
environment.
This
process
requires
integration
bottom-up
topdown
neuronal
activity,
which
centrally
mediated
by
basal
forebrain,
region
that
has
been
linked
series
cognitive
processes
such
as
attention
alertness.
Here,
we
review
latest
research
using
optogenetic
approaches
in
rodents
vivo
electrophysiological
recordings
are
shedding
light
on
role
this
region,
regulating
olfactory
processing
decisionmaking.
Moreover,
summarize
evidence
highlighting
anatomical
physiological
differences
forebrain
with
autism
spectrum
disorder,
could
underpin
sensory
abnormalities
they
exhibit,
propose
line
potential
opportunity
understand
neurobiological
basis
disorder.La
percepción
sensorial
es
una
de
las
funciones
cerebrales
más
fundamentales,
permitiendo
los
individuos
interactuar
manera
apropiada
con
el
entorno
y
adaptarse
un
ambiente
en
constante
cambio.
Este
proceso
requiere
la
integración
actividad
ascendente
descendente,
que
mediada
por
cerebro
(BF),
región
cerebral
ha
sido
asociada
serie
procesos
cognitivos,
como
estados
atención
alerta.En
este
trabajo
revisamos
últimas
investigaciones
han
utilizado
optogenética
registros
electrofisiológicos
iluminado
rol
del
BF
procesamiento
olfatorio
toma
decisiones.
Además,
resumimos
literatura
destaca
alteraciones
fisiológicas
anatómicas
trastornos
espectro
autista,
podrían
subyacer
anormalidades
presentan,
proponemos
esta
línea
investigación
posible
oportunidad
para
entender
bases
neurobiológicas
trastorno.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: June 7, 2024
Abstract
Parvalbumin
(PV)-expressing
GABAergic
neurons
of
the
basal
forebrain
(BFPVNs)
were
proposed
to
serve
as
a
rapid
and
transient
arousal
system,
yet
their
exact
role
in
awake
behaviors
remains
unclear.
We
performed
bulk
calcium
measurements
electrophysiology
with
optogenetic
tagging
from
horizontal
limb
diagonal
band
Broca
(HDB)
while
male
mice
performing
an
associative
learning
task.
BFPVNs
responded
distinctive,
phasic
activation
punishment,
but
showed
slower
delayed
responses
reward
outcome-predicting
stimuli.
Optogenetic
inhibition
during
punishment
impaired
formation
cue-outcome
associations,
suggesting
causal
learning.
received
strong
inputs
hypothalamus,
septal
complex
median
raphe
region,
they
synapsed
on
diverse
cell
types
key
limbic
structures,
where
broadcasted
information
about
aversive
propose
that
arousing
effect
is
recruited
by
stimuli
crucial
functions.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2020,
Volume and Issue:
unknown
Published: Dec. 2, 2020
Abstract
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.
Towards
this,
utilized
fiber
photometry
genetically
encoded
acetylcholine
indicator
GAChR2.0
temporal
patterns
olfactory-guided,
behaviors
We
show
reliably
increased
reward-seeking
was
strongly
suppressed
by
reward
delivery
go/no-go,
olfactory-cued
discrimination
task.
The
observed
transient
reduction
tone
mirrored
suppression
GABAergic
activity.
Together,
these
findings
suggest
changes
rapidly
reflect
rewardseeking
positive
reinforcement
impact