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.
