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Preferential ipsilateral influence of the posterior hypothalamus on the neocortex.

On the 10th--20th day after precollicular transection of the brain stem weak low-frequency electrical stimulation of the posterior hypothalamus preferentially activates the ipsilateral neocortex. After unilateral injury to the posterior hypothalamus, synchronous activity predominates in the ipsilateral neocortex. In premesencephalic animals weak single electrical stimulation of the posterior hypothalamus evokes the appearance of spindles in ipsilateral zones of the frontal cortex, whereas stronger single stimulation causes the diffuse generation of spindles in various parts of the neocortex. Besides this preferential unilateral effect, the influence of the posterior hypothalamus is found to be more strongly expressed in the frontal than in the occipital cortex. It is postulated that the posterior hypothalamus exerts its influence on the neocortex through the thalamic nuclei.

Animals↗

Effect of a local rise of temperature of the anterior hypothalamus on the electroencephalogram.

In chronic experiments on rabbits the anterior hypothalamic region was heated by means of water thermodes. Heating the anterior hypothalamus to +3.0 degrees C caused no change in the character of the initial EEG. Heating the anterior hypothalamus to +6.0 degrees C caused activation of the initially synchronized EEG. The EEG weakly activated by heating the anterior hypothalamus to between +1.0 and +2.0 degrees C could be synchronized; this effect depended on the strength of the activating influences of the experimental external situation on the animal. The threshold of EEG activation by heating the anterior thalamus was 1.5-2 times higher than the threshold of activation of the EEG by cooling the anterior hypothalamus. In every case a change in the temperature of the anterior hypothalamus evoked appropriate thermoregulatory responses.

Animals↗

Cyto- and chemoarchitecture of the hypothalamus of a wallaby ( Macropus eugenii) with special emphasis on oxytocin and vasopressinergic neurons.

We have studied the organization of the hypothalamus in an Australian diprotodontid metatherian mammal, the wallaby ( Macropus eugenii), using cytoarchitectural, histochemical and immunohistochemical techniques. Coronal sections of adult brains were processed for Nissl staining, histochemical reactivity (cytochrome oxidase, nicotinamide adenine dinucleotide phosphate diaphorase and acetylcholinesterase) and immunohistochemistry (antibodies to tyrosine hydroxylase, calbindin, calretinin, non-phosphorylated neurofilament protein, oxytocin and vasopressin). The distribution of immunoreactive neurons for these substances was mapped with the aid of a computer-linked microscope. In general, the wallaby hypothalamus showed a similar nuclear organization to that seen in rodents. The paraventricular nucleus could be divided into several subdivisions based on the different cellular parcellation, similar to that described in rodents. The ventromedial hypothalamic nucleus had cell-sparse dorsomedial and cell-dense ventrolateral subdivisions as seen in eutheria, suggesting a similar functional compartmentalization in all theria. The positions of tyrosine hydroxylase-positive neurons in the wallaby hypothalamus were also similar to those in eutheria. Oxytocin and vasopressinergic neurons were found in all the same major nuclear groups as seen in eutheria, although a nucleus circularis could not be identified. The general similarities between wallaby and eutherian hypothalamus indicate that the basic chemo- and cytoarchitectural features of the hypothalamus are common to eutheria and metatheria and validate the use of the wallaby as a mammalian model of wide applicability in investigations of hypothalamic functional development.

Acetylcholinesterase↗

Effect of prolactin on dopamine synthesis in medial basal hypothalamus: evidence for a short loop feedback.

Several procedures were utilized to study the effects of prolactin on dopamine synthesis in the medial basal hypothalamus of the rat. Elevation of serum prolactin was produced by the administration of trifluoperazine (5 mg/kg, i.p.) and resulted in a significant increase in the conversion of [3',5'-3H]tyrosine to dopamine when measured in slices of medial basal hypothalamus and striatum. Hypophysectomy abolished this effect of trifluoperazine in the medial basal hypothalamus but not in the striatum. In addition, the synthesis of dopamine was significantly elevated in slices of medial basal hypothalamus obtained from rats bearing pituitary tumor implants that secreted microgram quantities of prolactin. In contrast, the in vitro synthesis of dopamine in the striatum of such rats was increased by the secretory products in one tumor line but decreased in another compared to that observed in control animals. It is suggested that the ability of prolactin to accelerate the synthesis of dopamine in the medial basal hypothalamus might constitute a short loop feedback system that finely regulates prolactin secretion.

Animals↗

The alpha 1-noradrenergic antagonist prazosin decreases the concentration of estrogen receptors in female rat hypothalamus.

A series of experiments was performed to determine the effects of the alpha 1-noradrenergic antagonist, prazosin, on the concentration of estrogen receptors in female rat brain and pituitary gland. Prazosin caused a dose-dependent decrease in the concentration of cytosol estrogen receptors in mediobasal hypothalamus when injected 10 and 16 h prior to assay. The drug was without effect on the concentration of nuclear estrogen receptors in the absence of estradiol, indicating that the decreased concentration of cytosol estrogen receptors is not due to nuclear estrogen receptor accumulation. Scatchard analysis confirmed that prazosin treatment decreases the concentration of cytosol estrogen receptors without influencing the apparent affinity of the receptors for [3H]estradiol. The prazosin-induced decrease in the concentration of cytosol estrogen receptors in the mediobasal hypothalamus was transient with maximal effects occurring between 8 and 12 h after a single injection. Competition analysis confirmed that prazosin is not an effective competitor for binding to the estrogen receptor in vitro. The effects of prazosin on the estrogen receptor system could not be attributed to modulation of the levels of norepinephrine or dopamine. Assay of the levels of norepinephrine and dopamine in hypothalamus and preoptic area after prazosin injection revealed no effects of prazosin on the level of either of these catecholamines. An estradiol injection resulted in the predicted decrease in the concentration of estrogen receptors accumulating in hypothalamic cell nuclei, suggesting that the cytosol estrogen receptors that decrease in concentration are functional receptors. Prazosin treatment did not result in a decrease in the effectiveness of estradiol in the induction of cytosol progestin receptors in the mediobasal hypothalamus, suggesting that the cells are regulated by the alpha 1-noradrenergic system may not be those cells in which progestin receptors are also induced. These experiments provide further evidence that the noradrenergic system modulates the concentration of estrogen receptors, and perhaps sensitivity to estradiol, in some cells within the rat hypothalamus.

Adrenergic alpha-Antagonists↗

L-glutamate mapping of cardioreactive areas in the rat posterior hypothalamus.

The posterior hypothalamus has long been regarded as a CNS region that provides a sympatho-excitatory influence on the cardiovascular system and functions in thermoregulation as a heat-producing center. These ideas have been based on data derived from electrical stimulation and lesion experiments. These methods are now regarded as inadequate for accurate localization of CNS functions. In order to re-examine the function of the posterior hypothalamus, a chemical stimulation study was performed. Microinjections of the excitatory amino acid L-glutamate were made in the posterior hypothalamus of pentobarbital-anesthetized rats. This method was used in combination with autoradiography to localize [3H]glutamate, which was included with the injectate. No pressor responses were elicited from any site within the posterior hypothalamus. In contrast, chemical stimulation of the posterior periventricular hypothalamus produced large decreases in blood pressure (delta BP = 25 mm Hg) and in heart rate (delta HR = 30 bpm). Injections in the posterior hypothalamic nucleus elicited small reductions in blood pressure and heart rate. Injections in the dorsal hypothalamic area produced a similar small response. Injections ventral to the periventricular zone were also weakly reactive, but a significant elevation in rectal temperature was seen. To summarize, the most cardioresponsive area was within the periventricular zone caudal to the posterior hypothalamic nucleus and was situated near the fasciculus retroflexus.

Animals↗

Defense reaction elicited by injection of GABA antagonists and synthesis inhibitors into the posterior hypothalamus in rats.

Blockade of gamma-aminobutyric acid (GABA) in the posterior hypothalamic nucleus elicits cardiorespiratory stimulation in anesthetized rats. The present study was conducted to test the hypothesis that blockade of GABA in this cardiostimulatory area of the posterior hypothalamus in conscious animals would elicit a defense reaction characterised by a "fight or flight" response. Blockade of GABA was achieved by injecting bicuculline methiodide (BMI 1-25 ng) and picrotoxin (4-100 ng), two post-synaptic GABA antagonists and isoniazid (INH 35 and 70 micrograms), an inhibitor of the synthesis of GABA, bilaterally into the posterior hypothalamus through chronically implanted microinjection cannulae. All three drugs produced dose-dependent increases in locomotor activity, suggesting an "escape" reaction which was quantified as number of crossings and rearings. The effects of bicuculline and picrotoxin appeared immediately after the injection while those of isoniazid appeared much more slowly, attaining peak effects 24 +/- 1 min after injection. Injection of either strychnine (38 ng) into the posterior hypothalamus or bicuculline into the lateral hypothalamic area (LHA) or the dorso-medial/ventro-medial hypothalamus (DMH/VMH) did not elicit a significant increase in locomotor behavior. These results suggest that both the physiological and locomotor components of the hypothalamic defense reaction may be under tonic GABAergic inhibition in the region of the posterior hypothalamus.

Aggression↗

The hypothalamus receives major projections from the tuberomammillary nucleus in rat.

Projections from the tuberomammillary nucleus (TM) to widespread regions within the hypothalamus were evaluated using a combined immunohistochemical-retrograde fluorescent tracing procedure. Injections of Fluoro-gold into the anterior hypothalamus labelled TM neurons identified by their immunoreactivity for the enzyme adenosine deaminase (ADA). Small injections of Fluoro-gold into the posterior hypothalamus also led to the labelling of TM neurons. The numbers of ADA-immunoreactive axonal varicosities were 5 times greater in the hypothalamus than in most other brain regions. The results indicate that the hypothalamus represents a major projection area of the TM.

Adenosine Deaminase↗

The appearance of Fos protein-like immunoreactivity in the hypothalamus of developing rats in response to cold ambient temperatures.

This study examined cellular activity in the hypothalamus of developing rats in response to cold environmental temperatures. The appearance of the nuclear protein, Fos, in response to cold ambient temperatures in rats three to 35 days of age was used as a marker of neuronal activation. Fos-positive nuclei were first seen in response to cold ambient temperatures in the ventromedial nucleus at three days of age, the paraventricular nucleus at eight days of age, the preoptic-anterior hypothalamus at 10 days of age and the anterior hypothalamic nucleus at 21 days of age. The rectal temperature of the 10-day-old pups dropped by less than half that measured in the nine-day-old pups after 1 h in the cold. It is possible that the activation of neurons in the preoptic-anterior hypothalamus in the 10-day-old animal may contribute to the decreased hypothermia observed in the 10-day-old after 1 h in the cold. The high density of Fos-like immunoreactive-labeled nuclei in the preoptic-anterior hypothalamus in the 10-day-old rats that were exposed to the cold environment indicates increased neuronal activity at this site. The results suggest that, at least in the preoptic-anterior hypothalamus, the appearance of the cellular response to cold ambient temperatures is coincidental with a thermogenic response.

Acclimatization↗

Orexin-A regulates growth hormone-releasing hormone mRNA content in a nucleus-specific manner and somatostatin mRNA content in a growth hormone-dependent fashion in the rat hypothalamus.

The orexins or hypocretins are two neuropeptides involved in the regulation of diverse biological processes such as feeding, sleep and neuroendocrine function. Recent findings suggest a possible functional interaction between orexins, somatostatin and growth hormone-releasing hormone (GHRH) in the rat hypothalamus. In order to understand the possible functional linkage between orexins and these neuropeptides, we determined the effects of intracerebroventricular orexin-A administration on hypothalamic somatostatin and GHRH mRNA levels. Furthermore, we examined whether growth hormone (GH) mediates these interactions by using two animal models that showed GH deficiency: hypophysectomized rats and dwarf Lewis rats. Using in situ hybridization, our data showed that GHRH mRNA levels in the paraventricular nucleus of the hypothalamus are decreased after orexin-A treatment, without changes in the arcuate nucleus of the hypothalamus. On the other hand, orexin-A treatment induces a GH-dependent stimulatory effect on somatostatin mRNA content in the periventricular nucleus of the hypothalamus. Finally, we demonstrated, for the first time, that hypophysectomized rats and dwarf Lewis rats, two classical models of GH deficiency with alterations in sleep patterns, showed a marked reduction in the GHRH mRNA levels in the paraventricular nucleus of the hypothalamus. These data improve our understanding of the interactions among the different systems involved in the control and pathophysiology of food intake, sleep and GH secretion.

Animals↗

A comparative study of the effects of nitric oxide and carbon monoxide on the in vivo release of gonadotropin-releasing hormone and neuropeptide Y from rat hypothalamus during the estradiol-induced luteinizing hormone surge: estimation by push-pull perfusion.

Recent evidence suggests that nitric oxide (NO), a free radical gas, plays an important role in regulating the function of a variety of neuroendocrine systems. With respect to the hypothalamo-pituitary-gonadal axis, a stimulatory effect of NO on the release of gonadotropin-releasing hormone (GnRH) from rat hypothalamus has been demonstrated in vitro. However, no previous study has reported NO-stimulated secretion of GnRH from in vivo hypothalamus, and also the precise cellular site of action of NO within the GnRH neuronal system remains to be elucidated. In the present study, utilizing the push-pull perfusion technique of rat hypothalamus, we examined the effect of L-arginine (L-Arg), an NO donor, on the release of GnRH, neuropeptide Y and cyclic GMP (c-GMP), which is a pivotal second messenger molecule of the NO system. For comparison, we also examined the effect of carbon monoxide (CO), another putative gaseous neurotransmitter, using hematin, a CO donor. During the period of 11.00-18.00 h, we collected blood and hypothalamic perfusates from ovariectomized adult rats that had been implanted with an estradiol capsule 2 days before. During the entire period of observation, L-Arg (1.0 or 10 mM), hematin (10 or 100 microM) or artificial cerebrospinal fluid alone (as the control) was infused into the medial preoptic area (MPOA) where there are cell bodies of GnRH neurons, or the median eminence-arcuate nucleus complex (ME-ARC) where axon terminals of GnRH neurons are localized. Although 10 mM of L-Arg significantly stimulated GnRH and c-GMP, but not neuropeptide Y, levels in both the MPOA and ME-ARC, GnRH and c-GMP in the ME-ARC were already increased by 1.0 mM of L-Arg. By contrast, both concentrations of hematin were without effect at either site of the hypothalamus. This study is the first to demonstrate that NO is capable of stimulating GnRH release from rat hypothalamus in vivo. Our data also suggests that both cell bodies and axon terminals of GnRH neurons may be sites of action of NO. Our data do not support a previous study by other investigators that reported a stimulatory effect of CO on the GnRH release.

Animals↗

Distribution and release of immunoreactive thyroid-stimulating hormone in the rat hypothalamus: effects of thyroidectomy, hypophysectomy and treatment with thyroid hormones.

Immunoreactive thyroid-stimulating hormone (IR-TSH) has been detected in the hypothalamus and is released in vitro by a calcium-dependent mechanism when the tissue is depolarized. Recently, immunocytochemical studies have revealed that IR-TSH is present in thyrotropes in the pars tuberalis. Therefore, because these thyrotropes are associated with the median eminence, the area with the highest concentration of IR-TSH, it is of interest to determine if 'hypothalamic' IR-TSH is from neural or pituitary cells. We addressed this issue by studying the effects of hypophysectomy, thyroidectomy, or chronic administration of triiodothyronine (T3) or thyroxine (T4) on the distribution and in vitro release of IR-TSH in the hypothalamus. We reasoned that, if hypothalamic IR-TSH is dependent on the thyrotropes of the pars tuberalis, then changes in hypothalamic IR-TSH concentration and release should be parallel to those measured in pituitary extracts. IR-TSH was measured in tissue extracted in ice-cold 2% NaCl, with a final pH of 4.5. For the in vitro studies, tissues were incubated for 20-min periods in Krebs-Ringer bicarbonate buffer at 37 degrees C. In untreated rats, the concentration of IR-TSH is greater in the ventral than the dorsal portion of the hypothalamus (39.3 +/- 8.2 vs. 4.0 +/- 1.5 ng/mg wet wt.). Upon finer dissection of the hypothalamus into median eminence and anterior, middle, and posterior portions of the remainder, IR-TSH was only detectable in the middle hypothalamus (5.3 +/- 1.5 ng/mg), and the median eminence (149 +/- 41 ng/mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Regional distribution of type 2 thyroxine deiodinase messenger ribonucleic acid in rat hypothalamus and pituitary and its regulation by thyroid hormone.

To identify the specific locations of type 2 deiodinase (D2) messenger RNA (mRNA) in the hypothalamus and pituitary gland and determine its regulation by thyroid hormone, we performed in situ hybridization histochemistry, Northern analysis, and quantitative RT-PCR in euthyroid, hypothyroid, and hyperthyroid rats. By in situ hybridization histochemistry, silver grains were concentrated over ependymal cells lining the floor and infralateral walls of the third ventricle extending from the rostral tip of the median eminence (ME) to the infundibular recess, surrounding blood vessels in the arcuate nucleus (ARC), and in the ME adjacent to the portal vessels and overlying the tuberoinfundibular sulci. Silver grains also accumulated over distinct cells in the midportion of the anterior pituitary. In hypothyroid animals, an increase in signal intensity was observed in the caudal hypothalamus, and a marked increase in the number of positive cells occurred in the anterior pituitary. Microdissection of the hypothalamus for Northern and PCR analysis established the authenticity of D2 mRNA in the caudal hypothalamus, and confirmed that the majority of D2 mRNA is concentrated in this region. The distribution of D2 mRNA suggests its expression in specialized ependymal cells, termed tanycytes, originating from the third ventricle. Thus, the tanycyte is the source of the high D2 activity previously found in the ARC-ME region of the hypothalamus. The results indicate that tanycytes may have a previously unrecognized integral role in feedback regulation of TSH secretion by T4.

Animals↗

Light and electron microscopic studies on the medial forebrain bundle in the rat. ii. nerve terminals from the medial hypothalamus.

After the surgical interruption of connections between the medial and lateral hypothalamus of the rat axonal (transient) and nerve terminal degeneration was shown in the medial forebrain bundle (MFB) with light and electron microscopy. Following 1 mm long parasagittal cuts at various rostro-caudal levels the degeneration pattern within the MFB indicated a certain territoral arrangement of terminating fibres from the medial hypothalamus. After a parasagittal cut through the lateral retrochiasmatic area, degeneration was observed in the full length of the MFB. This suggests that a number of axons connect the medial and lateral hypothalamus through this area. With the aid of a parasagittal cut separating totally the medial and lateral hypothalamus, the degeneration of dendrites in the middle portion of the lateral hypothalamus was also revealed. These proved to derive from cells of the ventromedial nucleus.

Animals↗

The hypothalamus: anatomy and functions.

The neuroanatomy of the human hypothalamus is reviewed with special interest focused on its neuroendocrine role. The magnocellular neurons in the supraoptic and paraventricular nuclei are the site of synthesis of the nonapeptides antidiuretic hormone and oxytocin and their carriers, the neurophysins. They are in close relation with the posterior lobe of the pituitary which contains their axonal neurosecretory endings. The parvocellular neurons are scattered around the third ventricle, from the preoptic area towards the infundibulum. They control the adenohypophysis by the releasing hormones for thyrotropin (TRH), luteinizing hormone (LHGR), growth hormone (GHRH) and the inhibiting factor for growth hormone (somatostatin or SRIF) and prolactin (PIH). The mapping of the various hypothalamic structures responsible for these syntheses is still a problem although it progresses thanks to new techniques of immunocytochemistry. Recent so-called "hypothalamic" hormones like TRH and somatostatin for instance have been identified outside the hypothalamus. The posterior hypothalamus with other parts of the brain: the medial forebrain non myelinated bundle, in the lateral hypothalamus, connects the preoptic region to the midbrain. The stria terminalis connects the amygdala with the hypothalamus. Fibers of retinal origin terminate in the suprachiasmatic nuclei.

Animals↗

Leptin receptor immunoreactivity in chemically defined target neurons of the hypothalamus.

The adipose tissue-derived hormone leptin regulates body weight homeostasis by decreasing food intake and increasing energy expenditure. The weight-reducing action of leptin is thought to be mediated primarily by signal transduction through the leptin receptor (LR) in the hypothalamus. We have used immunohistochemistry to localize LR-immunoreactive (LR-IR) cells in the rat brain using an antiserum against a portion of the intracellular domain of LR that is common to all LR isoforms. The antiserum recognized the short and long isoforms of LR in transfected hematopoietic BaF3 cells. To examine the chemical nature of target cells for leptin, direct double-labeling immunofluorescence histochemistry was applied. The results show extensive distribution of LR-like immunoreactivity (LR-LI) in the brain with positively stained cells present, e.g., in the choroid plexus, cerebral cortex, hippocampus, thalamus, and hypothalamus. In the hypothalamus, strongly LR-IR neurons were present in the supraoptic nucleus (SON) and paraventricular nucleus (PVN), periventricular nucleus, arcuate nucleus, and lateral hypothalamus. Weaker LR-IR neurons were also demonstrated in the lateral and medial preoptic nuclei, suprachiasmatic nucleus, ventromedial and dorsomedial nuclei, and tuberomammillary nucleus. Confocal laser scanning microscopy showed LR-LI in the periphery of individual cells. In magnocellular neurons of the SON and PVN, LR-LI was demonstrated in vasopressin- and oxytocin-containing neurons. In parvocellular neurons of the PVN, LR-LI was demonstrated in many corticotropin-releasing hormone-containing neurons. LR-IR neurons were mainly seen in the ventromedial aspect of the arcuate nucleus, where LR-LI co-localized with neuropeptide Y. In the ventrolateral part of the arcuate nucleus, LR-LI was present in many large adrenocorticotropic hormone-IR proopiomelanocortin-containing neurons and in a few galanin-, neurotensin-, and growth hormone-releasing hormone-containing neurons. In the dorsomedial arcuate nucleus, few tyrosine hydroxylase (dopamine)-containing neurons were seen to have LR-LI. Melanin-concentrating hormone-containing neurons in the lateral hypothalamus had LR-LI. Based on the immunohistochemical results, possible interactions of leptin with brain mechanisms are discussed.

Animals↗

A cytoarchitectonic atlas of the mouse hypothalamus.

A description of the organization, areas, and cell groups within the hypothalamus of the mouse is presented in detail. Photomicrographs of cell-stained serial sections through the hypothalamus in frontal, sagittal and horizontal planes are included. The hypothalamus has been divided basically into medial and lateral parts with most well-defined cell groups or nuclei lying within the medial subdivision and surrounded by diffuse collections of cells referred to as areas. The heterogenetiy of cell types within most hypothalamic nuclei and areas has been emphasized with the consequent implications for heterogeneity of neuronal connections and of functions. Recently introduced neuroanatomical techniques permitting increased attention to the cellular level of organization have demonstrated precise connections and functional localization of cells within the hypothalamus. While cytoarchitectonic distinctions imply functional distinctions, morphological and experimental evidence suggest the existence also of systems of cells which transcend conventional cytoarchitectonic boundaries, the cells within each system being interconnected functionally or neuronally.

Animals↗

Localization and developmental pattern of vasoactive intestinal polypeptide binding sites in the human hypothalamus.

Using a quantitative in vitro autoradiographic approach, vasoactive intestinal polypeptide (VIP) binding site densities were compared in the post-mortem hypothalamus of human neonate/infant and adult. The densities were similar during development in most of the hypothalamic nuclei and areas examined underlying the stability of 125I-VIP binding sites in the post-mortem hypothalamus of young and adult individuals. However, the ventral part of the medial preoptic area, the medial, lateral, and supramammillary nuclei were characterized by an increase of 125I-VIP binding with age. In young and adult individuals, the highest densities of hypothalamic 125I-VIP binding sites were detected in the supraoptic and infundibular nuclei; the ependyma; the organum vasculosum of the lamina terminalis; the horizontal limb of the diagonal band of Broca; the ventral part of the medial preoptic area (in adult); the suprachiasmatic, paraventricular, and periventricular nuclei; and the medial and lateral mammillary nuclei in adult. Moderate densities were found in the vertical limb of the diagonal band of Broca, the bed nucleus of the stria terminalis, the ventral part of the medial preoptic area in neonate/infant, the medial and lateral mammillary nuclei in neonate/infant, the supramammillary nucleus in adult, the dorsal hypothalamic area, and the ventromedial nucleus. Low to moderate binding site densities were observed in the other hypothalamic regions of young or adult individuals. The nonspecific binding ranged from 15% of the total binding in the anterior hypothalamus to 20% in the mediobasal and posterior hypothalamic levels. Taken together, these results provide evidence for a large distribution of VIP binding sites in neonate/infant and adult human hypothalamus suggesting the implication of VIP in the development of this brain structure and the maintenance of its various functions.

Adult↗