Neuropeptide Y1 receptors inhibit N-type calcium currents and reduce transient calcium increases in rat dentate granule cells

Abstract

Neuropeptide Y (NPY) is far more abundant in the dentate gyrus than elsewhere in the hippocampal formation, but it does not alter the synaptic excitation of dentate granule cells (DGCs) as it does for pyramidal cells in areas CA1 and CA3. NPY inhibited depolarization-induced increases in intracellular Ca2+ concentrations ([Ca2+]i) in DGCs in hippocampal slices, without altering the resting [Ca2+]i. NPY inhibited Ca2+ currents (ICa) via a Y1 receptor in 84% of acutely isolated DGCs and via a Y2 receptor in 31% of the NPY-responsive cells tested. ICa inhibition was completely occluded by omega-conotoxin-GVIA but not by nimodipine. The inhibition of ICa was accompanied by a change in the time course of ICa activation in only 27% of NPY-responsive cells. Only 23% of DGCs responded to NPY when Ba2+ was substituted for extracellular Ca2+ and when [Ca2+]i was strongly buffered. Therefore, NPY inhibits an N-type ICa in DGCs, mainly via Y1 receptors. Furthermore, it seems that more than one mechanism, one of which may be sensitive to [Ca2+]i, may couple NPY receptors to the Ca2+ channels in DGCs. Because the release of dynorphin from DGCs depends in part on N-type currents, NPY receptors are poised to regulate the release of opioid peptides from DGC somata and dendrites.

The Effect of Intrahippocampal Injection of Group II and III Metobotropic Glutamate Receptor Agonists on Anxiety; the Role of Neuropeptide Y

“…Autoradiographic binding studies and in situ hybridization have shown that Y1 and Y2 receptors are quite abundant in the rat hippocampus (Dumont et al, 1990(Dumont et al, , 1992McQuiston et al, 1996;Wahlestedt and Reis, 1993;McQuiston et al, 1996). According to some earlier results obtained by our group and by other authors (Sajdyk et al, 1999;Wierońska et al, 2004Wierońska et al, , 2005, NPY shows anxiolytic activity in the amygdala, and this effect is mediated by Y1 receptors, as it is blocked by BIBO 3304.…”

Plasticity of neuropeptide Y in the dentate gyrus after seizures, and its relevance to seizure-induced neurogenesis

“…This is also suggested by electrophysiological studies, which have shown that NPY influences mossy fiber transmission by a presynaptic mechanism [10]. Both Y2 and Y5 receptors have been implicated in these effects [15,16].…”

“…Studies of Y1 receptor agonists reveal inhibitory effects on Ca 2+ entry into dendrites of granule cells [16]. Other studies suggest a potentially proconvulsant effect [17].…”

Upregulation of Gene Expression in Reward-Modulatory Striatal Opioid Systems by Sleep Loss

“…Sleep loss upregulates CNS food-reward systems BA Baldo et al localized in interneurons (Hendry et al, 1984;Karagiannis et al, 2009), and hippocampal NPY is found both in GABA interneurons (Sperk et al, 2007) and granule cells (McQuiston et al, 1996). The role of NPY in hippocampus is not fully understood; however, several studies suggest a role in cellular defenses against excitatory stress.…”

“…For example, NPY gene expression is upregulated by metabotropic glutamate receptor stimulation (Schwartzer and Sperk, 1998) and NPY in the dentate gyrus inhibits glutamate release (Whittaker et al, 1999) has anticonvulsive actions (Patrylo et al, 1999). NPY also reduces depolarization-induced Ca 2 þ influx into dentate granule cells (McQuiston et al, 1996), which could be responsible for NPY-induced inhibition of perforant pathway LTP (Whittaker et al, 1999). Hippocampal NPY may thus serve a neuroprotective role during conditions of cellular stress, but at the same time inhibit neuroplasticity relevant to learning.…”