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The Journal of Neuroscience, June 15, 2002, 22(12):4794-4804
Coordinate Release of ATP and GABA at In Vitro
Synapses of Lateral Hypothalamic Neurons
Young-Hwan
Jo and
Lorna W.
Role
Department of Anatomy and Cell Biology, Center for Neurobiology and
Behavior, Columbia University, College of Physicians and
Surgeons, New York, New York 10032
Autonomic and limbic information is integrated within the lateral
hypothalamus (LH), and excitability of LH neurons is important in the
control of feeding and behavioral arousal. Despite the prominent
expression of P2X-type ATP receptors throughout the hypothalamus, the role of ATP in LH excitability is not known. Perforated-patch-clamp recordings of synaptically coupled neurons from
both embryonic chick and postnatal mouse lateral hypothalamus in
vitro reveal robust stimulus-evoked purinergic synaptic
transmission. Suprathreshold activation elicits reliable and concurrent
release of ATP with GABA. Tetrodotoxin-resistant P2X receptor-mediated events are readily observed at LH synapses from the embryonic chick,
whereas GABA miniature postsynaptic currents (mPSCs) are recorded in innervated LH neurons from either embryonic chicks or
postnatal mice. Two distinct mPSCs are recorded at ATP-GABA cosynapses; one has a monoexponential decay phase and is modulated by
flunitrazepam, and the other has a decay phase that is best fit by a
sum of two exponential functions ( fast and
slow), and only the slow component
is affected by flunitrazepam. Bicuculline does not completely inhibit
all mPSCs. The remaining bicuculline-resistant mPSCs are blocked by
suramin, and their decay phase is briefer than that of GABAergic mPSCs.
Furthermore, at a holding potential intermediate for the reversal
potentials of GABAA and P2X receptors, little or no current
is observed, consistent with concomitant release (and detection) of
GABA and ATP. Together, our data suggest that a subset of spontaneous
and evoked PSCs arise from the concurrent activation of both
GABAA and P2X receptors.
Key words:
cotransmission; feeding; P2X receptor; plasticity; lateral hypothalamus; ATP; GABA; GABAA receptor
Copyright © 2002 Society for Neuroscience 0270-6474/02/22124794-11$05.00/0
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