Activation of N-methyl- d-aspartate receptors evokes calcium spikes in the dendrites of rat hypothalamic paraventricular nucleus neurons

Activation of dendritic voltage-dependent calcium (Ca 2+) conductances in neuroendocrine cells of the hypothalamus may underlie previously documented Ca 2+ spikes in these cells. The present study, in which whole-cell recordings were obtained from paraventricular nucleus neurons in a hypothalamic slice preparation, addresses this issue by directly activating dendritic N-methyl- d-aspartate receptors in the presence of tetrodotoxin. Application of tetrodotoxin abolished spontaneous action potentials in all paraventricular nucleus neurons tested ( n=27). Following tetrodotoxin, spikes were evoked by depolarizing current pulses, in an all-or-none fashion in the majority of cells ( n=20). Removal of extracellular Ca 2+ ( n=6) or addition of 500 μM CdCl 2 ( n=4) abolished the spikes in response to pulses. Repetitive spiking activity (in tetrodotoxin) was also observed following N-methyl- d-aspartate agonist application in 75% of the cells tested ( n=15). The spikes, underscored by a slow membrane depolarization, were abolished by the administration of CdCl 2 ( n=4). N-Methyl- d-aspartate agonist elicited a slow inward current in cells voltage-clamped at −60 mV ( n=5). Additionally, larger amplitude, transient inward currents were observed near the onset of the response. The activation threshold to elicit spikes following N-methyl- d-aspartate agonist application was significantly more negative (−54.6±3.6 mV) than the potential at which spikes were initiated as a result of depolarizing current injection (−32.3±1.8 mV; Student's t-test: P0.05), regardless of the stimulus used to initiate the spikes. These observations suggest that direct activation of N-methyl- d-aspartate receptors located on the dendrites of paraventricular nucleus neurons triggers Ca 2+ spikes. Although the precise function of these spikes is unclear, previous data reporting dendritic neuropeptide release in the paraventricular nucleus raise the possibility that dendritically initiated spikes may serve as a local signal to trigger such release.