Ghrelin affects behavioral and physiological responses, such as feeding or the activity of the HPA axis. Distribution of its receptor in central sites involved in neuroendocrine control, including the hypothalamic paraventricular nucleus, indicates that interplay with multiple neuropeptidergic systems underlies ghrelin's actions. We report that intracerebroventricular ghrelin increases c-Fos immunoreactivity of oxytocin neurons in magno and parvocellular portions of the paraventricular nucleus. The orexigenic response to ghrelin administered at the dose that activates oxytocin neurons can be further elevated by pretreatment with a selective oxytocin receptor antagonist. Our data suggest that oxytocin may be responsible for the mediation of some effects induced by ghrelin. Modifications in the activity of the oxytocin system may alter some of these effects.

Neocortical networks produce oscillations that often correspond to characteristic physiological or pathological patterns. However, the mechanisms underlying the generation of and the transitions between such oscillatory states remain poorly understood. In this study, we examined resonance in mouse layer V neocortical pyramidal neurons. To accomplish this, we employed standard electrophysiology to describe cellular resonance parameters. Bode plot analysis revealed a range of resonance magnitude values in layer V neurons and demonstrated that both magnitude and phase response characteristics of layer V neocortical pyramidal neurons are modulated by changes in the extracellular environment. Specifically, increased resonant frequencies and total inductive areas were observed at higher extracellular potassium concentrations and more hyperpolarised membrane potentials. Experiments using pharmacological agents suggested that current through hyperpolarization-activated cyclic nucleotide-gated channels (I(h) ) acts as the primary driver of resonance in these neurons, with other potassium currents, such as A-type potassium current and delayed-rectifier potassium current (Kv1.4 and Kv1.1, respectively), contributing auxiliary roles. The persistent sodium current was also shown to play a role in amplifying the magnitude of resonance without contributing significantly to the phase response. Although resonance effects in individual neurons are small, their properties embedded in large networks may significantly affect network behavior and may have potential implications for pathological processes.

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Unraveling the mechanisms underlying oscillatory behavior is critical for understanding normal and pathological brain processes. Here we used electrophysiology in mouse neocortical slices and principles of nonlinear dynamics to demonstrate how an increase in the N‐methyl‐d‐aspartic acid receptor (NMDAR) conductance can create a nonlinear whole‐cell current–voltage (I–V) relationship which leads to changes in cellular stability. We discovered two behaviorally and morphologically distinct pyramidal cell populations. Under control conditions, both cell types responded to depolarizing current injection with regular spiking patterns. However, upon NMDAR activation, an intrinsic oscillatory (IO) cell type (n = 44) showed a nonlinear whole‐cell I–V relationship, intrinsic voltage‐dependent oscillations plus amplification of alternating input current, and these properties persisted after disabling action potential generation with tetrodotoxin (TTX). The other non‐oscillatory (NO) neuronal population (n = 24) demonstrated none of these behaviors. Simultaneous intra‐ and extracellular recordings demonstrated the NMDAR’s capacity to promote low‐frequency seizure‐like network oscillations via its effects on intrinsic neuronal properties. The two pyramidal cell types demonstrated different relationships with network oscillation – the IO cells were leaders that were activated early in the population activity cycle while the activation of the NO cell type was distributed across network bursts. The properties of IO neurons disappeared in a low‐magnesium environment where the voltage dependence of the receptor is abolished; concurrently, the cellular contribution to network oscillation switched to synchronous firing. Thus, depending upon the efficacy of NMDAR in altering the linearity of the whole‐cell I–V relationship, the two cell populations played different roles in sustaining network oscillation.

N-Methyl-D-aspartate (NMDA) receptors have been implicated in epileptogenesis, but how these receptors contribute to epilepsy remains unknown. In particular, their role is likely to be complicated because of their voltage-dependent behavior. Here, the authors investigate how activation of NMDA receptors can affect the intrinsic production of oscillation and the resonance properties of neocortical pyramidal neurons from children with intractable epilepsy. Intracellular whole-cell patch clamp recordings in cortical slices from these patients revealed that pyramidal neurons do not produce spontaneous oscillation under control conditions. However, they did exhibit resonance around 1.5 Hz. On NMDA receptor activation, with bath-applied NMDA (10 μM), the majority of neurons produced voltage-dependent intrinsic oscillation associated with a change in the stability of the neuronal system as reflected by the whole-cell I-V curve. Furthermore, the degree of resonance was amplified while the frequency of resonance was shifted to lower frequencies (∼1 Hz) in NMDA. These results suggest that NMDA receptors may both promote the production of low-frequency oscillation and sharpen the response of the cell to lower frequencies. Both these behaviors may be amplified in tissue from patients with epilepsy, resulting in an increased propensity to generate seizures.