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,
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2020,
Volume and Issue:
unknown
Published: Dec. 20, 2020
Abstract
Cortical
sensory
areas
send
excitatory
projections
back
to
earlier
stage
of
processing.
Here,
we
uncover
for
the
first
time
existence
a
corticofugal
inhibitory
feedback
between
two
areas,
paralleling
well-documented
feedback.
In
olfactory
system,
reveal
that
subpopulation
GABAergic
neurons
in
anterior
nucleus
and
piriform
cortex
target
bulb.
These
long-range
inputs
synapse
with
both
local
output
bulb
neurons,
mitral
tufted
cells.
Optogenetic
stimulation
coupled
vivo
imaging
network
modeling
showed
activation
these
drives
net
subtractive
inhibition
spontaneous
odor-evoked
activity
as
well
Further,
cortical
enhanced
separation
population
odor
responses
cells,
but
not
Targeted
pharmacogenetic
silencing
axon
terminals
OB
impaired
discrimination
similar
mixtures.
We
propose
here
represents
new
circuit
motif
systems,
involved
refining
processing
perception.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2021,
Volume and Issue:
unknown
Published: July 6, 2021
Abstract
The
olfactory
bulb
(OB),
the
first
relay
for
odor
processing,
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
dynamics
these
afferents
are
still
unclear.
I
studied
how
BF
synaptic
inputs
modulate
activity
in
diverse
subtypes
periglomerular
(PG)
interneurons
using
optogenetic
stimulation
loose
cell-attached
or
whole-cell
patch-clamp
recording
OB
slices
adult
mice.
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
thereby
increasing
tonic
inhibition
principal
neurons.
Taken
together,
findings
suggest
modality-specific
can
orchestrate
glomeruli
multiple,
potentially
independent,
inhibitory
excitatory
target-specific
pathways.
Frontiers in Cellular Neuroscience,
Journal Year:
2023,
Volume and Issue:
16
Published: Jan. 6, 2023
In
the
olfactory
bulb
(OB),
a
large
population
of
axon-less
inhibitory
interneurons,
granule
cells
(GCs),
coordinate
network
activity
and
tune
output
principal
neurons,
mitral
tufted
(MCs),
through
dendrodendritic
interactions.
Furthermore,
GCs
undergo
neurogenesis
throughout
life,
providing
source
plasticity
to
neural
OB.
The
function
integration
in
OB
are
regulated
by
several
afferent
neuromodulatory
signals,
including
noradrenaline
(NA),
state-dependent
neuromodulator
that
plays
crucial
role
regulation
cortical
task-specific
decision
processes.
However,
mechanisms
which
NA
regulates
GC
not
fully
understood.
Here,
we
show
modulates
hyperpolarization-activated
currents
(I
h
)
via
activation
α
2
-adrenergic
receptors
(ARs)
adult-born
(abGCs),
thus
directly
acting
on
channels
play
essential
roles
regulating
neuronal
excitability
oscillations
brain.
This
modulation
affects
leading
an
enhancement
lateral
inhibition
onto
MCs.
subthreshold
resonance
GCs,
could
affect
temporal
abGCs.
Together,
these
results
provide
novel
mechanism
I
can
regulate
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: March 31, 2023
Abstract
Parvalbumin
(PV)-expressing
GABAergic
neurons
of
the
basal
forebrain
(BFPVNs)
were
proposed
to
serve
as
a
rapid
and
transient
arousal
system.
While
they
have
well-documented
role
in
regulation
sleep-wake
states,
whether
how
BFPVNs
participate
mediating
awake
behaviors
is
not
known.
To
address
this,
we
performed
bulk
calcium
imaging
recorded
single
neuronal
activity
from
horizontal
band
diagonal
Broca
(HDB)
while
mice
performing
an
associative
learning
task.
Genetically
identified
HDB
responded
with
distinctive,
phasic
activation
punishment.
In
contrast,
reward
only
elicited
slow
delayed
responses,
stimuli
predicting
behavioral
reinforcement
(reward
or
punishment)
followed
by
gradual
increase
BFPVN
firing
rates.
Optogenetic
inhibition
during
punishment
impaired
formation
cue-outcome
associations,
suggesting
causal
these
learning.
Mapping
input-output
connectivity
anterograde
mono-transsynaptic
retrograde
tracing
experiments
showed
that
received
strong
inputs
hypothalamus,
septal
complex
median
raphe
region,
synapsed
on
diverse
cell
types
key
structures
limbic
system
including
medial
septum,
retrosplenial
cortex
hippocampus.
Bulk
termination
regions
indicated
broadcast
information
about
aversive
multiple
downstream
targets.
We
propose
arousing
effect
recruited
crucial
functions
behaviors.
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,