L.P. Renaud

Facilitatory influence of noradrenergic afferents on the excitability of rat paraventricular nucleus neurosecretory cells.

The role of the A1 and A2 noradrenergic cell groups of the caudal medulla in regulating the activity of paraventricular nucleus neurosecretory cells was examined with electrophysiological methods in anaesthetized male Sprague‐Dawley rats. Antidromically identified neurosecretory cells were classified as vasopressin or oxytocin secreting on the basis of spontaneous firing patterns and responsivity to baroreceptor activation. The effect on cell firing of single pulses (25‐200 microA) delivered to either the A1 or A2 cell group areas was then examined using peri‐stimulus histograms. Stimulation of the A1 region enhanced the activity of 78% of putative vasopressin‐secreting neurones tested (n = 18), but failed to affect the activity of the majority (73%) of putative oxytocin‐secreting units (n = 15). A2 stimulation enhanced the firing rate of both putative vasopressin‐ (60%, total n = 14) and putative oxytocin‐secreting (70%, total n = 27) neurones. Destruction of the paraventricular nucleus catecholamine terminal plexus by pre‐treatment with the neurotoxin 6‐hydroxydopamine abolished the facilitatory effects of both A1 and A2 stimulation. These findings suggest that noradrenergic afferents of medullary origin facilitate the activity of paraventricular nucleus neurosecretory cells. The role of the projection from the A1 cell group appears to differ from that of the A2 group, however, in that its effects are specific to putative vasopressin‐secreting units.

Electrophysiological evidence that noradrenergic afferents selectively facilitate the activity of supraoptic vasopressin neurons

The functional role of the ascending projection from A1 noradrenergic neurons of the caudal ventrolateral medulla to the supraoptic nucleus of the hypothalamus was investigated by examining the effects of electrical stimulation of the A1 region on the activity of supraoptic neurons deemed to be vasopressinergic or oxytocinergic on the basis of basal firing patterns and responsivity to baroreceptor activation. A1 stimulation enhanced the activity of all putative vasopressin-secreting supraoptic neurons tested. This effect appeared to be selective in that no putative oxytocin-secreting neurons were excited by A1 stimulation. Destruction of the supraoptic noradrenergic terminal plexus by local application of the neurotoxin 6-hydroxydopamine abolished the facilitatory effects of A1 stimulation but did not noticeably alter basal activity patterns, nor the influence of baroreceptor inhibitory pathways. These findings suggest a facilitatory role for noradrenergic afferents in regulating the activity of neurohypophysially-projecting vasopressin neurons of the supraoptic nucleus.

Opposing α- and β-adrenergic mechanisms mediate dose-dependent actions of noradrenaline on supraoptic vasopressin neurones in vivo

Abstract The effects of pressure-applied noradrenaline (NA) on the activity of neurosecretory cells of the supraoptic nucleus (SON) were examined in anaesthetized male rats. Spontaneously active, antidromically identified neurosecretory cells were classified as vasopressin (VP)-secreting on the basis of activity patterns and responsiveness to baroreceptor activation. The probability of encountering VP units was enhanced by confining electrode penetrations to the caudal aspect of the SON. Application of low concentrations of NA (50–150 μM) excited 75% of putative VP neurones tested (n= 45), while very high concentrations (1–100 mM) were inhibitory (79%, n tested= 14). The excitatory effects of NA were blocked by the α1 antagonist prazosin (0.1–5 μM, n= 9) and mimicked by application of the α1 agonist methoxamine (300 μM–1mM, n= 29). The α2 agonist clonidine (800 μM–1 mM) also frequently elicited mild excitations (92%,n tested= 13); however, this was commonly followed by an extended period of quiescence. Neither the α2 antagonist yohimbine(5 μM, n = 4) nor the β-adrenoreceptor antagonist timolol (5–20 μM, n= 6) blocked NA-induced excitations. The inhibitory effects of high concentrations of NA, however, were blocked by the application of timolol (5–20 μM, n= 5). It is suggested that the excitatory effect of low concentrations of NA on VP neurones reflects the actions of this substance when endogenously secreted at normal sites of release within the SON.

Angiotensin II may mediate excitatory neurotransmission from the subfornical organ to the hypothalamic supraoptic nucleus: an anatomical and electrophysiological study in the rat

In the rat, it has been proposed that angiotensin II (AII) neurons in the subfornical organ, a midline circumventricular structure, participate in the activation of hypothalamic neurosecretory neurons and promote a rise in plasma vasopressin and oxytocin. In this study, we observed AII-immunoreactive fibers coursing throughout the supraoptic nucleus as well as in other magnocellular cell groups of the hypothalamus. Moreover, following retrograde transport of Fast blue deposited within the supraoptic nucleus, cell counts in our best case revealed that 40% of AII-immunoreactive neurons in subfornical organ contained Fast blue, and 46% of the retrogradely labeled subfornical organ cells contained AII. In separate electrophysiological studies, post-stimulus histograms from 18 of 28 supraoptic neurons displayed a 30-55% reversible reduction in the excitation evoked by an electrical stimulus in the subfornical organ during local pressure applications of 100 microM to 1 mM saralasin. In 2 of 14 other cells, tubocurare (100 microM) produced only a 10% reduction in subfornical organ excitation. These observations indicate that AII may mediate an excitatory input to supraoptic neurons from the subfornical organ.

Contrasting Actions of Amino Acids, Acetylcholine, Noradrenaline and Leucine Enkephalin on the Excitability of Supraoptic Vasopressin-Secreting Neurons

The preferential release of the neurohypophyseal hormones vasopressin and oxytocin by appropriate stimuli implies that neurons secreting each hormone receive different afferent connections and may the

Subfornical organ-supraoptic nucleus connections: An electrophysiologic study in the rat

Extracellular recordings from antidromically-identified neurosecretory cells in the rat supraoptic nucleus (SON) indicate that electrical stimulation (1 Hz, 50 microseconds, 200 microA) in the subfornical organ (SFO) alters the excitability of 89% (n = 31) of phasically-active (putative vasopressin-secreting) and 94% (n = 16) of continuously-active (putative oxytocin-secreting) neurons; 45% of cells display a long latency (mean 80.2 +/- 20.5 ms, S.D.) prolonged (150-350 ms) increase in excitability; 26% of cells demonstrate a similar excitation, preceded by a brief decrease in firing at a latency of 30.5 +/- 13.1 ms; 15% of cells display only a depression in their activity, lasting up to 150 ms. Ninety percent of non-neurosecretory (i.e. non-antidromic) neurons (n = 19) within or above th SON also display orthodromic excitatory or inhibitory responses to SFO stimulation; however, these cells usually respond with shorter latencies, and none demonstrate the prolonged excitation seen among neurosecretory cells. With SON stimulation, antidromic activation observed from 6 of 18 SFO neurons (latency range of 12-27 ms) confirms a projection from SFO to the SON area. These data suggest a predominantly facilitatory influence of SFO neurons on the excitability of both vasopressinergic and oxytocinergic neurosecretory cells in the rat, thereby supporting a role for the SFO in body water balance.

Pulsatile Growth Hormone Secretion: Suppression by Hypothalamic Ventromedial Lesions and by Long-Acting Somatostatin

Sequential blood samples, obtained from freely behaving, nonstressed male rats, showed a pulsatile pattern of growth hormone secretion with a mean interval between peaks of 68 minutes. The bursts of secretion were blocked by lesions of the hypothalamic ventromedial nuclei and by administration of a longacting preparation of synthetic somatostatin.

Subfornical Organ Efferents Influence the Excitability of Neurohypophyseal and Tuberoinfundibular Paraventricular Nucleus Neurons in the Rat

Electrical stimulation in the subfornical organ (SFO) alters the excitability of antidromically identified paraventricular nucleus neurons. Extracellular recordings demonstrate that the dominant effect of single stimuli delivered to the SFO on neurohypophyseal oxytocin and vasopressin containing neurons is an increase in excitability. In 35% of cells tested, this excitation showed a long latency (44.3 +/- 3.4 ms) prolonged duration (208.7 +/- 23.5 ms), while in 16% of the neurons the excitation observed may be described as short latency (24.7 +/- 1.8 ms) short duration (11.6 +/- 1.4 ms). Of the remaining cells antidromically identified as projecting to the posterior pituitary, 12% showed initial decreases in excitability following SFO stimulation while the remaining 37% were unaffected. Evidence is presented demonstrating that stimulation in the region of the SFO results in short latency (27.9 +/- 2.4 ms) short duration (7.8 +/- 0.7 ms) increases in excitability in 22% of antidromically identified PVN tuberoinfundibular neurons tested. These data provide electrophysiological evidence in support of the proposed role of the subfornical organ in the control of posterior and anterior pituitary function.

Noradrenergic Afferents Facilitate the Activity of Tuberoinfundibular Neurons of the Hypothalamic Paraventricular Nucleus

The role of ascending noradrenergic projections of medullary origin in regulating the activity of tuberoinfundibular neurons of the hypothalamic paraventricular nucleus (PVN) was examined in pentobarbital-anesthetized male Sprague-Dawley rats. Discrete electrical stimulation of either the A1 or the A2 noradrenaline cell group areas of the caudal medulla enhanced the probability of firing in a substantial proportion of antidromically identified tuberoinfundibular PVN cells tested. Notably, no inhibitory effects were observed. Destruction of the PVN noradrenergic terminal plexus by local application of the neurotoxin 6-hydroxydopamine 1 day prior to electrophysiological experiments abolished the effects of both A1 and A2 stimulation. These findings indicate that noradrenergic afferents can exert a facilitatory influence on the activity of a population of tuberoinfundibular PVN neurons, thus supporting earlier suggestions that central noradrenergic structures can enhance the release of certain anterior pituitary hormones.

An electrophysiological study of amygdalohypothalamic projections to the ventromedial nucleus of the rat

The influence of the amygdala on the activity of single neurons within the hypothalamic ventromedial nucleus (HVM) was studied in pentobarbital or urethane anesthetized rats. The results are summarized as follows: (1) Stimulation of different amygdaloid nuclei or of the stria terminalis (ST) evoked a prominent field potential within HVM and altered the spike discharge patterns of the majority of HVM neurons. (2) More than 80% of 428 HVM neurons tested with single amygdala shocks exhibited excitation or excitation-inhibition sequences; the remainder displayed inhibitory responses of 100-150 msec duration at latencies slightly longer than for most of the observed excitatory responses. ST stimulation also evoked excitation or excitation-inhibition sequences from 85% of 240 HVM neurons tested; of the remainder, those with spontaneous activity displayed inhibitory responses with durations of 100-150 msec at latencies slightly longer than for most observed excitatory responses. (3) Evoked potential interaction studies suggested that stimulation of either ST or the amygdala activated the same population of HVM neurons. Single cells tested with both amygdala and ST stimulation displayed similar patterns of response. HVM field potentials and single unit responses to amygdala stimulation were markedly diminished by lesions of ST. Thus, in the rat, only one pathway, i.e., the stria terminalis, contains amygdalofugal fibres to the ventromedial hypothalamic nucleus. (4) The orthodromic responses of HVM neurons were dependent on the frequency of amygdala stimulation. Less than 50% of HVM neurons responded to amygdala stimuli at frequencies greater than 33Hz. Many cells could not be activated at stimulation frequencies greater than 10 Hz, and the spontaneous discharges from certain HVM neurons were effectively abolished at this stimulation frequency. (5) Evidence of prominent postsynaptic inhibition was present throughout HVM. Seventeen HVM neurons displayed amygdala evoked unitary activity different from that of the majority of HVM neurons, and these cells were considered to represent possible inhibitory neurons. In contrast to most HVM neurons activated via probable monosynaptic amygdalohypothalamic pathways, these putative inhibitory neurons were apparently activated via polysynaptic pathways. (6) In summary, these results suggest that the amygdala exerts a prominent monosynaptic influence on the activity of many HVM neurons, coupled with polysynaptic activation of powerful local postsynaptic inhibitory mechanism. In the rat, these amygdala evoked events depend on the integrity of the stria terminalis.