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mise à jour du
8 avril 2004
1987; 20; 3; 749-755
Effects of septal and hippocampal stimuli on paraventricular nucleus neurons
D Saphier, S Feldman
Laboratory of Neurophysiology, Department of Neurology, Hadassah University Hospital and Hebrew University Medical School, Jerusalern, Israel


It is now established that neurosecretory cells synthesizing corticotrophin-releasing factor (CRF) are located within parvocellular comporients of the hypothalamic paraventricular nucleus (PVN) of the rat and send axon projections to the median eminence. Also located within these components are cell bodies synthesizing somatostatin, dopamine, vasopressin and oxytocin, and projecting also to the median eminence. The PVN also, contains magnocellular neurosecretory cells that synthesize and secrete oxytocin and vasopressin, hormones released from the neurohypophysis. Such oxytocin- and vasopressin-secreting cells may be distinguished in vivo by their neurohypophysial projections and different firing patterns. CRF-Secretory terminals at the level of the median eminence may also contain vasopressin and a similar co-secretion of CRF and oxytocin has been suggested for PVN neurons projecting to the neurohypophysis?
Secretion of adrenal corticosteroids, stimulated by release of adenohypophyseal adrenocorticotrophic hormone (ACTH), is believed to be dependent upon the electrical activity of CRF-secreting cells of the PVN. The activity of these cells is thought to be modified by a variety of afferent inputs from limbic structures in particular those known to modify adrenocortical secretion, e.g. septal stimulation has been shown to, inhibit adrenocortical secretion . The lateral septum has been shown to project extensively to the region of the PVN and such projections appear to be highly topographically organized.
Afferent projections to the lateral septum have been shown to arise from the dorsal hippocampus as well as other regions of the hippocampus, whilst projecting also to the hypothalamus and PVN. The hippocampal projections are highly organized within the lateral septum and may serve to mediate observed influences of the dorsal hippocampus upon adrenocortical secretion. The major effect of dorsal hippocampus stimulation upon neuronal activity within the lateral septum has been shown to be excitatory. Since the predominant effect of electrical stimulation of the hippocampus upon adrenocortical activity appears to be inhibitory, this may suggest an inhibitory interneuron system arising within the lateral septum and impinging upon CRF-secreting cells within the PVN.
Secretion of growth hormone is partly under inhibitory control by somatostatin, synthesized by cells within the parvocellular PVN and other hypothalamic loci. Stimulation of the hippocampus has been shown to increase plasma growth hormone levels and this may be due to an inhibition of somatostatinergic neuronal activity.
Specific projections arising from the lateral septum have been shown to synapse onto vasopressinsecreting cells of the PVN and electrophysiological studies have demonstrated a projection from the lateral septum to identified neurohypophysial neurosecretory cells of the PVN. However, the nature of this pathway remains uncertain. It was the purpose of this study to attempt to further define this projection and also to attempt to correlate the effects of lateral septum and dorsal hippocampus stimulation upon PVN neurons identified as projecting to the median eminence with the known influences of these limbic structures upon anterior pituitary hormone secretion. [...]
Discussion : The data presented in this study indicate that a substantial proportion of PVN neurons receive afferent synaptic inputs from lateral septum and dorsal hippocampus and that these inputs show a high degree of convergence. The observations confirm previous electrophysiological studies of the PVN and similar studies within the mediobasal hypothalamus.Anatomical fibre-tracting studies have demonstrated extensive innervation of the PVN and surrounding regions arising from the lateral septum but the results observed in our study following lateral septum stimulation do not preclude the possibility of stimulation of fibre tracts en route to the PVN. The responses of PVN neurons recorded in our study appeared to be highly organized with respect to their firing patterns and electroanatomical identity. Thus, there was a uniform inhibition of those cells within the CRF- and somatostatin-rich components of the PVNwhich were identified as projecting to the median eminence, following stimulation of both lateral septum and dorsal hippocampus. These data correspond with the predominantly inhibitory influences of these limbic structures upon adrenocortical secretion and with the facilitatory influences of the hippocampus upon growth hormone secretion. On the other hand, those identified as neurohypophysial neurosecretory cells showed a heterogeneity of responses following either site of stimulation, with a greater proportion of excitatory responses recorded from phasically active, vasopressin-secreting cells, including those identified as projecting to the median eminence.
Swanson et al. reported that specific populations of lateral septal neurons are labelled retrogradely when microinjections of tracer are centred in the parvocellular components of the PVN, known to contain the neuronal perikarya of CRF- and somatostatin-secreting cells.` Such cells project to the median eminence` and it is reasonable to assume that some of the neurons identified as projecting to the median eminence in our study may have been somatostatin- or CRF-secreting cells although the PVN does also contain other cellular components? The lateral septum has been shown to subserve a predominantly inhibitory role in the control of adrenocortical secretion and the inhibitory responses recorded from PVN cells, antidromically identified as projecting to the median eminence, perhaps indicates that some of the cells may have been those secreting CRF.
The role of the dorsal hippocampus in the control of adrenocortical secretion has also been described as being of an inhibitory nature. As in the case of the results obtained following lateral septum stimulation, the primary response of PVN neurons identified as projecting to the median eminence, following dorsal hippocampus stimulation, was inhibition. Extensive, topographically organized projections to the LS have been identified as arising from the dorsal hippocampus and electrophysiological study has verified these data. The terminal fields of the hippocampo-septal projections appear to be in the same regions of the septum shown to contain cell bodies with projections to the region of the PVN. In view of these data and of the inhibitory role of the dorsal hippocampus in the control of adrenocortical activity, it seems likely that a hippocampo-septal pathway to the PVN, influencing CRF-secreting neuronal activity, may exist. This concept is supported by our data indicating that the responses of cells recorded in our study showed a high degree of convergence following the two stimuli. In particular, this was the case for those cells identified as projecting to the median eminence. Alternatively, the responses recorded may have been mediated by other hippocampal projections, arising from, e.g. the subiculum, which has previously been shown to, project to the PVN but stimulation of which produces predominantly excitatory responses from cells in the PVN identified as projecting to the median eminence. In view of the observation that hippocampal stimulation elevates growth hormone secretion, it is possible that some of the cells inhibited by the stimulation were somatostatin-secreting, since this peptide inhibits growth hormone secretion.
Responses of vasopressin- and oxytocin-secreting neurosecretory cells within the PVN have previously been demonstrated as being both excitatory and inhibitory in nature following lateral septum stimulation. The results of our study are similar regarding such cells, although the phasically firing, vasopressin-secreting neurons showed a greater number of excitatory responses following lateral septum stimulation than the continuously firing neurons, some of which may have been oxytocin-secreting cells. Poulain et al did not find this to be the case for similar cells within the supraoptic nucleus, when inhibition of identified vasopressin-secreting cells was the predominant response following lateral septum stimulation. In our study we employed a stimulus intensity somewhat greater than in the abovementioned study and this may have served to 'override' the inhibitory influence that these authors demonstrated. The inhibitory effect of lateral septum stimulation upon the continuously active (oxytocinsecreting) cells is, however, more in accord with this last study. It should be noted that since some of the continuously active cells fired slowly with irregular patterns of activity, it is not necessarily the case that none of these cells secreted vasopressin and may have been recruited to phasic activity with sufficient osmotic stimulation. If such cells were indeed vasopressin-secreting, they may have been those excited by the stimulation.
The only PVN cells identified as projecting to the median eminence and excited by either site of stimulation were phasically active, vasopressin-secreting. Vasopressinergic innervation of the median eminence is believed to serve a dynamic, stimulatory role in the regulation of adrenocortical secretion.Activation of these cells following dorsal hippocampus (and lateral septum) stimulation may thus produce a transient increase in adrenocortical secretion, as has been reported following dorsal hippocampus stimulation. Such an increase mediated by vasopressin could then be inhibited in the longterm, by a downregulation of CRF secretion as discussed above. The hippocampus is known to be involved in the feedback regulation of ACTH secretion by adrenal glucocorticoids. In the absence of these steroids, following adrenalectomy, it has been demonstrated that the incidence of vasopressin coexistence within CRF-secretion cells increases? Whether such cells are phasically active under either condition is not known but such knowledge may provide valuable information regarding the neural and glucocorticoid feedback control of their activity and may also assist in the interpretation of the results of the present study with respect to the differential innervation of continuously or phasically active cells by hippocampal-septal pathways. Similarly, the significance of our results in the light of the demonstrated coexistence of CRF and oxytocin in hypothalamoneurohypophysial neurons remains complex and uncertain.
Conclusion : Our results suggest that hippocampo-septal efferent pathways may provide a predominantly excitatory input to vasopressin-secreting cells of the PVN. In contrast, the effects upon putative somatostatin- or CRF-secreting cells are inhibitory. The results may correlate with previous reports regarding the involvement of these limbic structures in the neural regulation of adenohypophysial hormone secretion.