Segregated basal ganglia output pathways correspond to genetically divergent neuronal subclasses
Cell Reports,
Год журнала:
2025,
Номер
44(4), С. 115454 - 115454
Опубликована: Март 27, 2025
Язык: Английский
Segregated basal ganglia output pathways correspond to genetically divergent neuronal subclasses
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 29, 2024
The
basal
ganglia
control
multiple
sensorimotor
behaviors
though
anatomically
segregated
and
topographically
organized
subcircuits
with
outputs
to
specific
downstream
circuits.
However,
it
is
unclear
how
the
anatomical
organization
of
output
circuits
relates
molecular
diversity
cell
types.
Here,
we
demonstrate
that
major
nucleus
ganglia,
substantia
nigra
pars
reticulata
(SNr)
comprised
transcriptomically
distinct
subclasses
reflect
its
progenitor
lineages.
We
show
these
are
within
SNr,
project
targets
in
midbrain
hindbrain,
receive
inputs
from
different
striatal
subregions.
Finally,
mouse
also
identifiable
human
SNr
neurons,
suggesting
genetic
evolutionarily
conserved.
These
findings
provide
a
unifying
logic
for
developmental
specification
diverse
neurons
controlling
specialized
brain
regions.
Язык: Английский
Stimulation of the Medial SNr Promotes Sustained Motor Recovery and Counteracts Parkinsonian Pathophysiology in Dopamine Depleted Mice
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 15, 2024
Abstract
Dopamine
loss
alters
the
activity
of
neural
circuits
in
basal
ganglia,
contributing
to
motor
symptoms
Parkinson’s
disease
and
catalepsy.
Treatments
that
reduce
ganglia
pathophysiology
alleviate
but
require
maintenance.
Cell-type
specific
interventions
can
provide
sustained
therapeutic
benefits,
a
lack
understanding
pathways
involved
limits
translation.
Here,
we
establish
patterns
neuromodulation
electrophysiological
biomarkers
at
level
output
predict
duration
effects.
Focal
activation
neurons
ventromedial
substantia
nigra
reticulata
(SNr)
engaged
gradual
recovery
movement
persisted
for
hours
after
treatment,
accompanied
by
persistent
reduction
parkinsonian
pathophysiology.
Global
SNr
inhibition,
as
prescribed
classic
rate
model,
provided
only
transient
effects
on
did
not
reverse
network
These
findings
represent
important
steps
towards
developing
strategies
aim
repair,
rather
than
simply
mask,
circuit
dysfunction
disease.
Язык: Английский