bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Sept. 22, 2023
During
brain
development,
neural
circuits
undergo
major
activity-dependent
restructuring.
Circuit
wiring
mainly
occurs
through
synaptic
strengthening
following
the
Hebbian
"fire
together,
wire
together"
precept.
However,
select
connections,
essential
for
circuit
are
transient.
They
effectively
connected
early
in
but
strongly
diminish
during
maturation.
The
mechanisms
by
which
transient
connectivity
recedes
unknown.
To
investigate
this
process,
we
characterize
thalamocortical
inputs,
depress
onto
somatostatin
inhibitory
interneurons
employing
optogenetics,
chemogenetics,
transcriptomics
and
CRISPR-based
strategies.
We
demonstrate
that
contrast
to
typical
mechanisms,
is
non-canonical
involves
metabotropic
signaling.
Specifically,
metabotropic-mediated
transcription,
of
guidance
molecules
particular,
supports
elimination
connectivity.
Remarkably,
found
developmental
process
impacts
development
normal
exploratory
behaviors
adult
mice.
Science Advances,
Journal Year:
2024,
Volume and Issue:
10(15)
Published: April 10, 2024
-methyl-d-aspartate
receptors
(NMDARs)
and
other
ionotropic
glutamate
(iGluRs)
mediate
most
of
the
excitatory
signaling
in
mammalian
brains
response
to
neurotransmitter
glutamate.
Uniquely,
NMDARs
composed
GluN1
GluN3
are
activated
exclusively
by
glycine,
conventionally
mediating
inhibitory
when
it
binds
pentameric
glycine
receptors.
The
GluN1-3
vital
for
regulating
neuronal
excitability,
circuit
function,
specific
behaviors,
yet
our
understanding
their
functional
mechanism
at
molecular
level
has
remained
limited.
Here,
we
present
cryo-electron
microscopy
structures
GluN1-3A
bound
an
antagonist,
CNQX,
agonist,
glycine.
show
a
1-3-1-3
subunit
heterotetrameric
arrangement
unprecedented
pattern
GluN3A
orientation
shift
between
glycine-bound
CNQX-bound
structures.
Site-directed
disruption
unique
interface
structure
mitigated
desensitization.
Our
study
provides
foundation
distinct
structural
dynamics
that
linked
function
NMDARs.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: June 26, 2024
Abstract
During
brain
development,
neural
circuits
undergo
major
activity-dependent
restructuring.
Circuit
wiring
mainly
occurs
through
synaptic
strengthening
following
the
Hebbian
“fire
together,
wire
together”
precept.
However,
select
connections,
essential
for
circuit
are
transient.
They
effectively
connected
early
in
but
strongly
diminish
during
maturation.
The
mechanisms
by
which
transient
connectivity
recedes
unknown.
To
investigate
this
process,
we
characterize
thalamocortical
inputs,
depress
onto
somatostatin
inhibitory
interneurons
employing
optogenetics,
chemogenetics,
transcriptomics
and
CRISPR-based
strategies
mice.
We
demonstrate
that
contrast
to
typical
mechanisms,
is
non-canonical
involves
metabotropic
signaling.
Specifically,
metabotropic-mediated
transcription,
of
guidance
molecules
particular,
supports
elimination
connectivity.
Remarkably,
found
process
impacts
development
normal
exploratory
behaviors
adult
Journal of Neurochemistry,
Journal Year:
2024,
Volume and Issue:
168(11), P. 3663 - 3684
Published: July 29, 2024
The
neurotransmitter
glycine
is
an
agonist
at
the
strychnine-sensitive
receptors.
In
addition,
it
has
recently
been
discovered
to
act
two
new
receptors,
excitatory
receptor
and
metabotropic
receptor.
Glycine's
roles
have
most
extensively
investigated
in
spinal
cord,
where
known
play
essential
pain,
itch,
motor
function.
contrast,
less
about
supraspinal
glycinergic
functions,
their
contributions
pain
circuits
are
largely
unrecognized.
As
neurons
absent
from
cortical
regions,
a
clearer
understanding
of
how
modulates
could
reveal
pharmacological
targets.
This
review
aims
synthesize
published
research
on
glycine's
role
adult
brain,
highlighting
regions
signaling
may
modulate
responses.
was
achieved
through
scoping
methodology
identifying
several
key
circuitry
involved.
Therefore,
this
unveils
critical
gaps
for
potential
pain-associated
responses,
encouraging
researchers
consider
neurotransmission
more
widely
when
investigating
neural
mechanisms
pain.
