Expression of c-fos Protein in Rat Brain Elicited by Electrical and Chemical Stimulation of the Hypothalamic Paraventricular Nucleus

Abstract

The functional connectivity of the paraventricular nucleus of the hypothalamus (PVN) was studied by assessing the expression of the immediate early gene, c-fos, after unilateral stimulation of this structure in urethane-anesthetized rats. Electrical stimulation for 1 h (10 s on, 10 s off; 15-40 µA at 20 Hz) was accompanied by increases in mean arterial pressure (13-29 mm Hg). In these animals, ipsilateral increases in numbers of neurons with Fos-like immunoreactivity (FLI) were immunohistochemically demonstrated in the insular cortex, lateral septum, medial amygdala, hypothalamus, lateral division of the parabrachial nucleus (PBN) of the pons and the nucleus of the tractus solitarius (NTS) and ventrolateral medulla (VLM). Numbers of cells with FLI were quantitated in five areas known for their roles in autonomic function: arcuate nucleus, ventromedial hypothalamus, lateral PBN, NTS (at three levels) and VLM (caudal and rostral). In each case, stimulation of the PVN led to significant differences in number of neurons with FLI on the side ipsilateral to the stimulation compared to the contralateral side. To eliminate effects associated with stimulation of fibers of passage in the vicinity of the PVN, the results after electrical stimulation were compared to those obtained in animals in which the PVN was chemically stimulated unilaterally with the excitatory amino acid L-glutamate (5 one-minute infusions of 50 nl, 0.5 M glutamate over 1 h). Mean arterial pressure was increased after each injection (7–13 mm Hg), and significant differences in numbers of neurons with FLI between sides were maintained in all five areas except the NTS caudal to, and at, the level of the area postrema. An increase in neurons with FLI in the piriform cortex of all animals including controls may be due to injury-induced activation of target neurons from the PVN. These data illustrate that electrical and chemical stimulation of the PVN leads to simultaneous activation of neurons in many targets. All of the target areas studied receive direct projections from the PVN, although multisynaptic projections may also contribute to activation of target neurons.

Estrogen in the Paraventricular Nucleus Attenuates l -Glutamate–Induced Increases in Mean Arterial Pressure Through Estrogen Receptor β and NO

“…Microinjections of L-glutamate (50 nmol, 100 nL) into the PVN increased MAP, HR, and the AUC for the MAP and HR responses. Our results are consistent with previous studies in conscious 33,34 and anesthetized rats, 35 which showed that microinjections of L-glutamate (25 to 100 nmol) into the PVN increase BP by 7 to 16 mm Hg. We found that E2 (10 pmol) injected into the PVN before L-glutamate attenuated the pressor response but did not affect the tachycardia.…”

Increase of Extracellular Glutamate and Expression of Fos‐Like Immunoreactivity in the Ventral Tegmental Area in Response to Electrical Stimulation of the Prefrontal Cortex

“…These results are consistent with other studies showing that electrical stimulation induces the expression of Fos protein (Menetrey et al, 1989;Erikson and Millhorn, 1991;Fu and Beckstead, 1992;Krukoff et al, 1992;Sandner et al, 1992;Krukoff et al, 1994). We can rule out the possibility that antidromic activation of dopamine fibers projecting to PFC contributed to the expression of Fos-like JR in the VTA since the parameters of stimulation used in our study were well below those required for antidromic activation of dopamine neurons themselves (Yeomans et al, 1988).…”

“…The application of exogenous glutamate agonists, especially NMDA, has been shown to increase the expression of Fus protein at local sites or through multisynaptic pathways (Cole et al, 1989;Sonnenberg et al, 1989;Aronin et al, 1991;Berretta et al, 1992;Krukoff et al, 1994;un et al, 1994). Thus, the present data are consistent with the hypothesis that the expression of Fus protein by electrical stimulation results from transsynaptic activation of VTA neurons by glutamate released from PFC efferent excitatory projections.…”

DC electrical field-induced c-fos expression and growth stimulation in multicellular prostate cancer spheroids

“…The data of the present study indicate stimulation of immediate-early response genes as revealed by anti-c-fos immunohistochemistry. The c-fos immediate early gene is induced in various preparations by several stress factors, including light (Yoshida et al, 1995), photodynamic therapy (Kick et al, 1996), hyperosmolar solutions (Wollnik et al, 1993), ischaemia, hypoxia, mechanical stimuli (Goldspink et al, 1995) and electrical nerve stimulation (Krukoff et al, 1994). Additionally, transient transcription of the c-fos gene has been reported during serum stimulation of quiescent cells in monolayer culture (Pai and Bird, 1994).…”

“…A theoretical estimation of membrane potential change was performed for MCS of different diameters (Figure 2A the induced maximum membrane potential in MCSs is higher in large spheroids than small spheroids. At a critical membrane potential of 1 V, dielectric breakdown occurs in biological membranes (Weaver, 1993 reported in several studies (Sisken et al, 1993;Krukoff et al, 1994;Goldspink et al, 1995;Yoshida et al, 1995). As c-fos is a well-known mediator of cell proliferation, the expression of c-fos in MCSs after electrical field exposure was evaluated by immunohistochemistry.…”