Vasoactive Intestinal Polypeptide Cells Research Articles

Hypersensitivity to Distractors in Fragile X Syndrome from Loss of Modulation of Cortical VIP Interneurons.

Attention deficit is one of the most prominent and disabling symptoms in Fragile X syndrome (FXS). Hypersensitivity to sensory stimuli contributes to attention difficulties by overwhelming and/or distracting affected individuals, which disrupts activities of daily living at home and learning at school. We find that auditory or visual distractors selectively impair visual discrimination performance in humans and mice with FXS but not in typically developing controls. In both species, males and females were examined. Vasoactive intestinal polypeptide (VIP) neurons were significantly modulated by incorrect responses in the poststimulus period during early distractor trials in WT mice, consistent with their known role as error signals. Strikingly, however, VIP cells from Fmr1 -/- mice showed little modulation in error trials, and this correlated with their poor performance on the distractor task. Thus, VIP interneurons and their reduced modulatory influence on pyramidal cells could be a potential therapeutic target for attentional difficulties in FXS.SIGNIFICANCE STATEMENT Sensory hypersensitivity, impulsivity, and persistent inattention are among the most consistent clinical features of FXS, all of which impede daily functioning and create barriers to learning. However, the neural mechanisms underlying sensory over-reactivity remain elusive. To overcome a significant challenge in translational FXS research we demonstrate a compelling alignment of sensory over-reactivity in both humans with FXS and Fmr1 -/- mice (the principal animal model of FXS) using a novel analogous distractor task. Two-photon microscopy in mice revealed that lack of modulation by VIP cells contributes to susceptibility to distractors. Implementing research efforts we describe here can help identify dysfunctional neural mechanisms associated not only with sensory issues but broader impairments, including those in learning and cognition.

Rate and oscillatory switching dynamics of a multilayer visual microcircuit model.

The neocortex is organized around layered microcircuits consisting of a variety of excitatory and inhibitory neuronal types which perform rate- and oscillation-based computations. Using modeling, we show that both superficial and deep layers of the primary mouse visual cortex implement two ultrasensitive and bistable switches built on mutual inhibitory connectivity motives between somatostatin, parvalbumin, and vasoactive intestinal polypeptide cells. The switches toggle pyramidal neurons between high and low firing rate states that are synchronized across layers through translaminar connectivity. Moreover, inhibited and disinhibited states are characterized by low- and high-frequency oscillations, respectively, with layer-specific differences in frequency and power which show asymmetric changes during state transitions. These findings are consistent with a number of experimental observations and embed firing rate together with oscillatory changes within a switch interpretation of the microcircuit.

Output from VIP cells of the mammalian central clock regulates daily physiological rhythms

The suprachiasmatic nucleus (SCN) circadian clock is critical for optimising daily cycles in mammalian physiology and behaviour. The roles of the various SCN cell types in communicating timing information to downstream physiological systems remain incompletely understood, however. In particular, while vasoactive intestinal polypeptide (VIP) signalling is essential for SCN function and whole animal circadian rhythmicity, the specific contributions of VIP cell output to physiological control remains uncertain. Here we reveal a key role for SCN VIP cells in central clock output. Using multielectrode recording and optogenetic manipulations, we show that VIP neurons provide coordinated daily waves of GABAergic input to target cells across the paraventricular hypothalamus and ventral thalamus, supressing their activity during the mid to late day. Using chemogenetic manipulation, we further demonstrate specific roles for this circuitry in the daily control of heart rate and corticosterone secretion, collectively establishing SCN VIP cells as influential regulators of physiological timing.

Neuromodulation Leads to a Burst-Tonic Switch in a Subset of VIP Neurons in Mouse Primary Somatosensory (Barrel) Cortex.

Neocortical GABAergic interneurons expressing vasoactive intestinal polypeptide (VIP) contribute to sensory processing, sensorimotor integration, and behavioral control. In contrast to other major subpopulations of GABAergic interneurons, VIP neurons show a remarkable diversity. Studying morphological and electrophysiological properties of VIP cells, we found a peculiar group of neurons in layer II/III of mouse primary somatosensory (barrel) cortex, which showed a highly dynamic burst firing behavior at resting membrane potential that switched to tonic mode at depolarized membrane potentials. Furthermore, we demonstrate that burst firing depends on T-type calcium channels. The burst-tonic switch could be induced by acetylcholine (ACh) and serotonin. ACh mediated a depolarization via nicotinic receptors whereas serotonin evoked a biphasic depolarization via ionotropic and metabotropic receptors in 48% of the population and a purely monophasic depolarization via metabotropic receptors in the remaining cells. These data disclose an electrophysiologically defined subpopulation of VIP neurons that via neuromodulator-induced changes in firing behavior is likely to regulate the state of cortical circuits in a profound manner.

An inhibitory pull-push circuit in frontal cortex.

Push-pull is a canonical computation of excitatory cortical circuits. Here we identify a pull-push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP) expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feed-back pull-push influence on excitatory neurons – an inversion of the canonical push-pull of feed-forward input.

The Role of VIP in Social Behavior: Neural Hotspots for the Modulation of Affiliation, Aggression, and Parental Care.

Although the modulation of social behaviors by most major neurochemical systems has been explored, there are still standouts, including the study of vasoactive intestinal polypeptide (VIP). VIP is a modulator of circadian, reproductive, and seasonal rhythms and is well known for its role in reproductive behavior, as it is the main vertebrate prolactin-releasing hormone. Originally isolated as a gut peptide, VIP and its cognate receptors are present in virtually every brain area that is important for social behavior, including all nodes of the core "social behavior network" (SBN). Furthermore, VIP cells show increased transcriptional activity throughout the SBN in response to social stimuli. Using a combination of comparative and mechanistic approaches in socially diverse species of estrildid finches and emberizid sparrows, we have identified neural "hotspots" in the SBN that relate to avian affiliative behavior, as well as neural "hotspots" that may represent critical nodes underlying a trade-off between aggression and parental care. Specifically, we have found that: (1) VIP fiber densities and VIP receptor binding in specific brain sites, such as the lateral septum, medial extended amygdala, arcopallium, and medial nidopallium, correlate with species and/or seasonal differences in flocking behavior, and (2) VIP cells and fibers within the anterior hypothalamus-caudocentral septal circuit relate positively to aggression and negatively to parental care while VIP elements in the mediobasal hypothalamus relate negatively to aggression and positively to parental care. Thus, while a given behavior or social context likely activates VIP circuitry throughout the SBN and beyond, key brain sites emerge as potential "hotspots" for the modulation of affiliation, aggression, and parental care.

Parvalbumin- and vasoactive intestinal polypeptide-expressing neocortical interneurons impose differential inhibition on Martinotti cells.

Disinhibition of cortical excitatory cell gate information flow through and between cortical columns. The major contribution of Martinotti cells (MC) is providing dendritic inhibition to excitatory neurons and therefore they are a main component of disinhibitory connections. Here we show by means of optogenetics that MC in layers II/III of the mouse primary somatosensory cortex are inhibited by both parvalbumin (PV)- and vasoactive intestinal polypeptide (VIP)-expressing cells. Paired recordings revealed stronger synaptic input onto MC from PV cells than from VIP cells. Moreover, PV cell input showed frequency-independent depression, whereas VIP cell input facilitated at high frequencies. These differences in the properties of the two unitary connections enable disinhibition with distinct temporal features.

Diverse Ensembles of Inhibitory Interneurons

In this issue of Neuron, Karnani etal. (2016) show that ensembles of specific types of inhibitory interneurons generate coordinated activity in mouse visual cortex. They also describe chemical and electrical synaptic mechanisms that may enable diverse interneuron ensembles to function as distinct operational units.

Inhibitory and excitatory networks balance cell coupling in the suprachiasmatic nucleus: A modeling approach

Neuronal coupling contributes to circadian rhythms formation in the suprachiasmatic nucleus (SCN). While the neurotransmitter vasoactive intestinal polypeptide (VIP) is considered essential for synchronizing the oscillations of individual neurons, γ-aminobutyric acid (GABA) does not have a clear functional role despite being highly concentrated in the SCN. While most studies have examined the role of either GABA or VIP, our mathematical modeling approach explored their interplay on networks of SCN neurons. Tuning the parameters that control the release of GABA and VIP enabled us to optimize network synchrony, which was achieved at a peak firing rate during the subjective day of about 7Hz. Furthermore, VIP and GABA modulation could adjust network rhythm amplitude and period without sacrificing synchrony. We also performed simulations of SCN networks to phase shifts during 12h:12h light-dark cycles and showed that GABA networks reduced the average time for the SCN model to re-synchronize. We hypothesized that VIP and GABA balance cell coupling in the SCN to promote synchronization of heterogeneous oscillators while allowing flexibility for adjustment to environmental changes.

Nesting behavior is associated with VIP expression and VIP–Fos colocalization in a network-wide manner

Many species, including humans, engage in a series of behaviors that are preparatory to the arrival of offspring. Such “nesting behaviors” are of obvious importance, but relevant neuroendocrine mechanisms remain little studied. We here focus on the potential roles of vasoactive intestinal polypeptide (VIP) in the performance of appetitive and consummatory nesting behaviors in male and female zebra finches (Taeniopygia guttata). Using combined immunocytochemistry for Fos and in situ hybridization for VIP, we now show that many VIP cell groups show increased transcriptional activity in response to nest building in male and female zebra finches. Particularly strong data come from the preoptic area (medial preoptic area and medial preoptic nucleus), where VIP–Fos co-expression correlates positively with three different measures of nesting behavior, as does the number of VIP-expressing cells. Remarkably, we find that VIP mRNA and/or VIP–Fos co-expression is correlated with nesting behavior in virtually every brain area that we examined, including the medial amygdala (anterior and posterior), medial bed nucleus of the stria terminalis, medial preoptic area, medial preoptic nucleus, anterior hypothalamus, ventromedial hypothalamus, periaqueductal gray complex (central gray and nucleus intercollicularis), and ventral tegmental area. Near-significant effects are also obtained in the tuberoinfundibular hypothalamus. Although most correlations are positive, negative correlations are observed for the VIP cell group of the anterior hypothalamus, a population that selectively promotes aggression, and also the periaqueductal gray complex. These data demonstrate a network-wide relationship between peptide production and social behavior that is, to our knowledge, unparalleled by other peptidergic modulators.

An aggression-specific cell type in the anterior hypothalamus of finches

The anterior hypothalamus (AH) is a major integrator of neural processes related to aggression and defense, but cell types in the AH that selectively promote aggression are unknown. We here show that aggression is promoted in a very selective and potent manner by dorsal AH neurons that produce vasoactive intestinal polypeptide (VIP). Fos activity in a territorial finch, the violet-eared waxbill (Estrildidae: Uraeginthus granatina) is positively related to aggression in the dorsal AH, overlapping a population of VIP-producing neurons. VIP is known to promote territorial aggression in songbirds, and thus we used antisense oligonucleotides to selectively block AH VIP production in male and female waxbills. This manipulation virtually abolishes aggression, reducing the median number of displacements in a 3-min resident-intruder test from 38 in control subjects to 0 in antisense subjects. Notably, most antisense and control waxbills exhibit an agonistic response such as a threat or agonistic call within 2 s of intrusion. Thus, antisense subjects clearly classify intruders as offensive, but fail to attack. Other social and anxiety-like behaviors are not affected and VIP cell numbers correlate positively with aggression, suggesting that these cells selectively titrate aggression. Additional experiments in the gregarious zebra finch (Estrildidae: Taeniopygia guttata) underscore this functional specificity. Colony-housed finches exhibit significant reductions in aggression (primarily nest defense) following AH VIP knockdown, but no effects are observed for social preferences, pair bonding, courtship, maintenance behaviors, or anxiety-like behaviors. To our knowledge, these findings represent a unique identification of an aggression-specific cell type in the brain.

Reproductive hormones, hepatic deiodinase messenger ribonucleic acid, and vasoactive intestinal polypeptide-immunoreactive cells in hypothalamus in the heat stress-induced or chemically induced hypothyroid laying hen

Heat stress (HS) effects on reproductive and thyroid hormones have been well documented; however, mechanisms of action are not well understood. Two studies were conducted to determine whether HS-induced and hypothyroid-induced effects are similar in the laying hen, with regard to reproductive hormones and vasoactive intestinal polypeptide (VIP)-immunoreactive cells in the hypothalamus. In study 1, thirty 32-wk-old Hy-Line W-36 laying hens, housed at 22 degrees C, were cannulated. On d 0 and then on d 1 to 5 of HS (35 degrees C, 50% RH), a daily blood sample was obtained and assayed for triiodothyronine (T(3)), thyroxine (T(4)), 17beta-estradiol (E(2)), progesterone (P(4)), prolactin (PRL), and VIP, and T(3):T(4)was calculated. On d 0, 1, 3, and 5, livers were obtained for hepatic type I deiodinase mRNA (cDI-1) determination. In study 2, eighty 32-wk-old hens were randomly assigned to 4 treatments of 20 birds each: 1) HS (36.5 degrees C, 50% RH), 2) thiouracil-induced hypothyroidism (HY), 3) HY + T(4) administration, and 4) control (22 degrees C). Beginning on d 1 of the 5-d study, daily blood samples (3.0 mL) were removed and assayed as in study 1. On d 5, brains were removed from 3 hens/treatment and immunoreactivity of VIP cells was determined. In study 1, HS reduced E(2), P(4), T(3) (P = 0.0001), T(3):T(4) ratio (P = 0.0078), and hepatic type I deiodinase mRNA (P = 0.0204) and increased T(4) (P = 0.0013); there was no effect on VIP or PRL. In study 2, HS and HY reduced T(3), T(3):T(4) ratio, and E(2) (P = 0.0001) and increased PRL (P = 0.0045); HS alone decreased P(4) (P = 0.0001). In HY + T(4), plasma E(2) and PRL were similar to control. Vasoactive intestinal polypeptide increased in plasma of HY birds, but there was no effect of HS or HY + T(4). Immunoreactive VIP cells increased (P = 0.0036) in nucleus inferior hypothalami of HS and HY brains. In HY + T(4), VIP immunoreactive cell numbers were similar to control. It appears that HY induced chemically or by HS exerts similar effects on reproductive hormones in the hen; the results suggest involvement of the VIP-PRL pathway even though peripheral blood concentrations were not consistent between studies.

Secretin mRNA in the Subdivision of Primary Sensory Neurons in the Trigeminal Ganglion of Rats

The primary sensory neurons use glutamate as a major neurotransmitter. Several neuropeptides are also found in these neurons. In our laboratory we demonstrated secretin-like immunoreactivity in primary sensory neurons of several species including human, rat and cat. In the present experiment utilizing in situ hybridization, we have demonstrated for the first time that secretin is not only immunostained but is also expressed in the primary sensory neurons of the trigeminal ganglion of male rats. In intact rats, secretin mRNA was not observed; we had to use intracerebroventricular colchicine administration to induce the expression of secretin. Secretin was expressed in about 5% of the cells in all the three subdivisions of the trigeminal ganglion. The secretin-synthetizing cells were large and medium sized, and their mean diameter was about 50 μm. When we compared the percentage and the size of secretin to that of calcitonin gene-related peptide (CGRP), substance-P (SP) and vasoactive intestinal polypeptide (VIP) cells, it was found that CGRP, SP and VIP are present in about 15-20% of the cells and their mean diameter is about 20-25 μm. The morphometric data indicate that secretin is present in a subdivision of neurons that is different from the subdivision of the CGRP, SP and VIP cells. It is suggested that secretin may modulate the function of the primary neurotransmitter.

Effect of concomitant progesterone administration or the effect of removal of estrogen capsule on changes caused by long-term estrogen treatment in pituitary VIP immunoreactivities

In the anterior pituitary besides the classical tropic hormones, peptides of a small molecular weight are also synthesized. One of them is the vasoactive intestinal polypeptide (VIP). VIP immunoreactivity is readily detected in human and monkey pituitaries; however, in the rat VIP immunoreactive cells were observed in about 50% of intact rats. In estrogen treated rats VIP immunoreactive cells were observed in the anterior pituitary of all animals. In this work, we have examined the effect of long-term sexual steroid treatments on the VIP immunoreactivity of the anterior pituitary using diethylstilbestrol (DES) or progesterone (P) filled capsules. The effectiveness of steroid treatments was tested by the measurement of plasma prolactin (PRL) level and by the appearance of prolactinoma. DES enhanced the plasma PRL level and 5months later it induced prolactinomas, the concomitant P treatment prevented both the elevation of plasma PRL level and the formation of prolactinomas. These results indicated that there was enough steroid in the capsules. There was a positive correlation between the duration of DES influence and the number of VIP immunoreactive cells. Two months after the implantation of DES there was a considerable number of VIP cells in the anterior pituitary, and 5months after implantation the number of VIP cells was greatly increased so as to form a VIP-oma. Concomitant implantation of P prevented the formation of VIP-oma. Two months after the implantation, the DES capsule was removed. Already 2months after removal the number of VIP cells approximated to the control level. It has been concluded that P can prevent the undesired effect of DES not only on the PRL, but on the VIP immunoreactivity as well.

Adaptive changes of gastro-entero-pancreatic system endocrine cells in the black-spotted pond frog Rana nigromaculata after fasting

Abstract Changes in distribution density, morphology and secretory content of endocrine cells in the gastro- entero-pancreatic system of black-spotted frogs Rana nigromaculata before and after fasting were investigated using immunohistochemistry and antisera to six gut hormones. Six types of endocrine cells were detected in the digestive tract of Rana nigromaculata, including 5-hydroxytryptamine (5-HT), gastrin (GAS), somatostatin (SOM), glucagon (GLU), pancreatic polypeptide (PP) and vasoactive intestinal polypeptide (VIP) cells. After fasting, the density of 5-HT cells in the esophagus, cardia and fundus, GAS cells in the fundus and pylorus, PP cells in the fundus decreased significantly (P < 0.01), while SOM cells in the cardia, GLU cells in the rectum increased significantly (P < 0.01). The cytoplasmic processes of 5-HT cells became shorter or not detectable. The secretory content of GAS cells reduced in the cardia. The positive immunostaining reaction in the perinuclear region of SOM cells in the cardia, fundus and pylorus became weaker, while the staining intensity in the periphery of these cells became stronger. VIP cells were not detectable in the whole digestive tract after fasting. Five types of endocrine cells were found in the pancreas of Rana nigromaculata, including 5-HT, GAS, SOM, GLU and PP cells. After fasting, the density of 5-HT cells decreased slightly (P > 0.05), while SOM, GAS, GLU and PP cells increased significantly (P < 0.01). Furthermore, the secretory content of GLU cells increased significantly. Considering their functionalities, our results indicate that the changes of GEP endocrine cells in Rana nigromaculata responded adaptively to starvation-induced stress.

Vasopressin: more than just an output of the circadian pacemaker? Focus on “Vasopressin receptor V1a regulates circadian rhythms of locomotor activity and expression of clock-controlled genes in the suprachiasmatic nuclei”

the timing of physiological events is carefully controlled so that incompatible processes do not compete and complementary functions coincide. Given the pivotal role of the hypothalamus in homeostatic regulation, the discovery that a master circadian pacemaker resides in this region was not

Regional differences in circadian period within the suprachiasmatic nucleus

In mammals, circadian rhythms are driven by a pacemaker located in the suprachiasmatic nucleus (SCN), which is composed of multiple, single-cell oscillators. Isolated SCN tissue shows clear circadian oscillation in release of arginine vasopressin (AVP) in organotypic slice cultures. Previously, we reported that the oscillators in the dorsal SCN have shorter periods than those in the ventral part. Here, we examined whether a correlation between the period and the rostral–caudal co-ordination could exist. The rostral, central and caudal SCN were cultured separately and the periods of circadian rhythms of AVP release were measured. The rostral and caudal parts of the SCN showed shorter periods than the central SCN. Together with previous findings, it is suggested that the shorter period region originates from AVP containing areas, while the longer period region corresponds with vasoactive intestinal polypeptide (VIP) containing cells. In our VIP-immunoreactive slices, the application of VIP antagonists shortened the periods of the AVP-releasing rhythm. These data indicate that the oscillators in AVP cells have short periods and are entrained by VIP cells to form a single integrated rhythm.

Immunoreactive vasoactive intestinal polypeptide and vasopressin cells after a protein malnutrition diet in the suprachiasmatic nucleus of the rat

The aim of the present study was to evaluate the effects of prenatal and postnatal protein deprivation on the morphology and density of vasopressin (VP) and vasoactive intestinal polypeptide (VIP) immunoreactive neurons in the suprachiasmatic nucleus (SCN) of young rats. Female Wistar rats were fed either 6% (malnourished group) or 25% (control group) casein diet five weeks before conception, during gestation and lactation. After weaning, the pups were maintained on the same diet until sacrificed at 30 days of age. The major and minor axes, somatic area and the density of VP- and VIP-immunoreactive neurons were evaluated in the middle sections of the SCN. The present study shows that chronic protein malnutrition (ChPM) in VP neurons induces a significant decrease in number of cells (-31%,) and a significant increase in major and minor axes and somatic area (+12.2%, +21.1% and +15.0%, respectively). The VIP cells showed a significant decrease in cellular density (-41.5%) and a significant increase in minor axis (+13.5%) and somatic area (+10.1%). Our findings suggest that ChPM induces abnormalities in the density and morphology of the soma of VP and VIP neurons. These alterations may be a morphological substrate underlying circadian alterations previously observed in malnourished rats.

Histamine and VIP‐positive Mast Cells in Renal Blood Vessels of Domestic Swine

Introduction: Histamine and vasoactive intestinal polypeptide (VIP) are well known biogenic amines (substances), which rapidly elute from the mast cell granules under physiological conditions. They play an important role in the smooth muscle cells motility.Aim: The aim of the study was to investigate histamine‐ and VIP‐positive mast cells in the wall of pig kidney blood vessels in concern to their role of motility of smooth muscle cells and renal haemodynamics, respectively.Material and Methods: Extra‐ and intraorgan renal blood vessels taken immediately after slaughtering of eight 6–8 months pigs were studied. Tissue samples were immersion fixed in 0.05 Mcacodylate buffer, pH 7.2, containing 2% paraformaldehyde and 0.2% glutaraldehyde for 5 days at 4°C. After fixation, tissue blocks were rinsed in 30% sucrose in distilled water at 4°C for 1–3 days. Cryostat sections (20–30 μm thick) were prepared and thawed in 0.05 M cacodylate buffer, pH 2, overnight. Immunocytochemical procedure started for free‐floating sections which were incubated in 1.2% hydrogen peroxide in methanol for 30 min, and rinsed in 0.1 M phosphate buffered saline (PBS), pH 7.4, for 15 min. Afterwards, sections were incubated with the primary antibodies in a dilution of 1:100 (histamine) and in vasoactive intestinal polypeptide (VIP) 1:1000 for 24 h at room temperature (RT), then rinsed in 0.1 M PBS, pH 7.4. Incubation succeeded: first, with biotinylated anti‐rabbit (histamine) and anti‐mouse VIP antibodies in a dilution of 1:20 for 4 h, and rinses in 0.1 M PBS, pH 7.4, and in 0.05 M tris‐HCl buffer, pH 7.5, for 10 min. Peroxidase activity was localized by using a mixture of 3 mg 3,3’ diaminobenzidine (DAB), in 15 ml 0.005 M Tris‐HCl buffer, pH 7.5, and 36 ml 1 % hydrogen peroxide for 10–20 min. Finally, a rinse in 0.01 M PBS, pH 7.4, was undertaken.Immunochemicals: The antibodies used were rabbit anti‐histamine (H7403) and rabbit anti‐vasoactive intestinal peptide (VIP), or (PEPA41) (Sigma, Saint Louis, Missouri, USA).Results and Discussion: It was established that VIP‐positive mast cells were located in the media and in the adventitia of large arterial vessels and renal vein, as well. Histamine positive mast cells were found mostly in the intima of renal artery and in the other layers of the wall. Both VIP and histamine mast cells were observed next to small arteries and veins in the fat tissue, around extraorgan blood vessels. Our finding suggest to mast cells participation in the smooth muscle cells motility and the maintenance of local homeostasis, as well.

Arginine‐vasopressin and vasointestinal polypeptide rhythms in the suprachiasmatic nucleus of the mouse lemur reveal aging‐related alterations of circadian pacemaker neurons in a non‐human primate

The suprachiasmatic nucleus (SCN) of the hypothalamus, the mammalian circadian pacemaker, is entrained by external cues and especially by photic information. Light is transmitted primarily via the retinohypothalamic tract, which terminates in the ventral part (or core) of the SCN, where vasoactive intestinal polypeptide (VIP)-containing neurons are located. VIP cells are mainly intrinsic and project to the dorsal part (or shell) of the SCN, where neurons containing arginine-vasopressin (AVP) reside. As aging leads to marked changes in the expression of circadian rhythms, we examined in primates whether age-related decay in biological rhythmicity is associated with changes in the oscillation of peptide expression in SCN neurons. We used double immunohistochemistry and quantitative analysis in the SCN of mouse lemurs, which provide a unique model of aging in non-human primates. In adult animals, VIP-positive and AVP-positive SCN neurons exhibited daily rhythms of their number and immunostaining intensity: AVP immunoreactivity peaked during the second part of the day, and VIP peaked during the night. In aged mouse lemurs, the peaks of AVP and VIP immunopositivity were significantly shifted, so that AVP was most intense at the beginning of the night, whereas VIP peaked at the beginning of daytime. The results show that the circadian rhythm of neuropeptides in the SCN is modified by aging in primates, with a differential regulation of the two main peptidergic cell populations. These changes may affect the ability of the SCN to transmit rhythmic information to other neural target sites, and thereby to modify the expression of some biological rhythms.