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The Journal of Neuroscience, October 22, 2003, 23(29):9639-9649

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Cellular/Molecular
Target-Specific Neuropeptide Y-Ergic Synaptic Inhibition and Its Network Consequences within the Mammalian Thalamus

Qian-Quan Sun,¹ Scott C. Baraban,² David A. Prince,¹ and John R. Huguenard¹

¹Department of Neurology and Neurological Sciences, Stanford School of Medicine, Stanford, California 94305, and ²Department of Neurological Surgery, University of California, San Francisco, San Francisco, California 94143

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 (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--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.

Key words: neuropeptide Y; endogenous neuropeptide; IPSPs; GIRK channels; burst firing; oscillations

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Received May 23, 2003; revised September 2, 2003; accepted September 2, 2003.

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				J. Brill, M. Lee, S. Zhao, R. D. Fernald, and J. R. Huguenard Chronic valproic acid treatment triggers increased neuropeptide y expression and signaling in rat nucleus reticularis thalami. J. Neurosci., June 21, 2006; 26(25): 6813 - 6822. [Abstract] [Full Text] [PDF]

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