Target-specific neuropeptide Y-ergic synaptic inhibition and its network consequences within the mammalian thalamus.
Neuropeptides are commonly colocalized with classical neurotransmitters, yet there is little evidence for peptidergic neurotransmission in the mammalian CNS. We performed whole-cell patch-clamp recording from rodent thalamic brain slices and repetitively stimulated corticothalamic fibers to strongly activate NPY-containing GABAergic reticular thalamic (RT) neurons. This resulted in long-lasting (approximately 10 sec) feedforward slow IPSPs (sIPSPs) in RT cells, which were mimicked and blocked by NPY1 (Y1) receptor agonists and antagonists, respectively, and were present in wild-type mice but absent in NPY-/- mice. NPYergic sIPSPs were mediated via G-proteins and G-protein-activated, inwardly rectifying potassium channels, as evidenced by sensitivity to GDP-beta-S and 0.1 mm Ba2+. In rat RT neurons, NPYergic sIPSPs were also present but were surprisingly absent in the major synaptic targets of RT, thalamic relay neurons, where instead robust GABA(B) IPSPs occurred. In vitro oscillatory network responses in rat thalamus were suppressed and augmented by Y1 agonists and antagonists, respectively. These findings provide evidence for segregation of postsynaptic actions between two targets of RT cells and support a role for endogenously released NPY within RT in the regulation of oscillatory thalamic responses relevant to sleep and epilepsy.
Department of Neurology and Neurological Sciences, Stanford School of Medicine, Stanford, California 94305, USA.
Qian-Quan
QQ
Sun
Scott C
SC
Baraban
David A
DA
Prince
John R
JR
Huguenard
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D009478:Neuropeptide Y / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D051381:Rats; D017207:Rats, Sprague-Dawley; D017476:Receptors, Neuropeptide Y / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D013788:Thalamus / Q000166:cytology / Q000502:physiology*
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D009478:Neuropeptide Y; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor