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Antiepileptic Actions of Neuropeptide Y in the Mouse Hippocampus Require Y5 Receptors
Author(s) -
Baraban Scott C.
Publication year - 2002
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.43.s.5.13.x
Subject(s) - excitatory postsynaptic potential , neuropeptide y receptor , hippocampal formation , neurotransmission , postsynaptic potential , population spike , inhibitory postsynaptic potential , neuroscience , population , hippocampus , receptor , endocrinology , chemistry , medicine , biology , neuropeptide , environmental health
Summary: Purpose: Recent evidence suggests an antiepileptic role for neuropeptide Y (NPY) in the central nervous system. The precise receptor subtypes mediating the inhibitory actions of NPY in the hippocampal formation, however, remain unclear. In vitro studies suggest a role for Y2 receptors in modulating excitatory hippocampal synaptic transmission and epileptiform discharge. In vivo studies implicate Y5 receptors. Here we used pharmacologic tools and Y5‐receptor knockout mice to examine the role of Y5 receptors in mediating the antiexcitatory and antiepileptic actions of NPY in the hippocampal formation. Methods: Hippocampal slices were obtained from age‐matched wild‐type (WT; 129 s3/svimj) and Y5‐receptor knockout (Y5R KO) mice generated on the same background strain. Extracellular or whole‐cell voltage‐clamp recordings were obtained in area CA3 pyramidale. Evoked population spikes or excitatory postsynaptic currents were monitored during bath application of NPY, NPY 13‐36 , or human pancreatic polypeptide (hPP). In some slices, zero‐magnesium cerebrospinal fluid (CSF) was used to evoke spontaneous epileptiform discharges. Results: NPY and NPY agonists with preference for either Y2 (NPY 13‐36 ) or Y5 (hPP) receptor subtypes caused a significant reduction in population spike and excitatory postsynaptic current (EPSC) amplitudes in slices from WT mice. NPY (and NPY agonists) also suppressed zero‐magnesium epileptiform burst discharge in slices from WT mice. In contrast, bath application of NPY, NPY 13‐36 , or hPP had no effect in slices from Y5R KO mice. Conclusions: NPY modulates excitatory synaptic transmission and inhibits limbic seizure activity in the mouse hippocampus. The antiepileptic actions of NPY, in the mouse, appear to require activation of hippocampal Y5 receptors.