Neuronal Stability, Volumetric Changes, and Decrease in GFAP Expression of Marmoset (Callithrix jacchus) Subcortical Visual Nuclei During Aging.

The physiological aging process is well known for functional decline in visual abilities. Among the components of the visual system, the dorsal lateral geniculate nucleus (DLG) and superior colliculus (SC) provide a good model for aging investigations, as these structures constitute the main visual pathways for retinal inputs reaching the visual cortex. However, there are limited data available on quantitative morphological and neurochemical aspects in DLG and SC across lifespan. Here, we used optical density to determine immunoexpression of glial fibrillary acidic protein (GFAP) and design-based stereological probes to estimate the neuronal number, total volume, and layer volume of the DLG and SC in marmosets (Callithrix jacchus), ranging from 36 to 143 months of age. Our results revealed an age-related increase in total volume and layer volume of the DLG, with an overall stability in SC volume. Furthermore, a stable neuronal number was demonstrated in DLG and superficial layers of SC (SCv). A decrease in GFAP immunoexpression was observed in both visual centers. The results indicate region-specific variability in volumetric parameter, possibly attributed to structural plastic events in response to inflammation and compensatory mechanisms at the cellular and subcellular level. Additionally, the DLG and SCv seem to be less vulnerable to aging effects in terms of neuronal number. The neuropeptidergic data suggest that reduced GFAP expression may reflect morphological atrophy in the astroglial cells. This study contributes to updating the current understanding of aging effects in the visual system and stablishes a crucial foundation for future research on visual perception throughout the aging process.

Blue light exposure-dependent improvement in robustness of circadian rest-activity rhythm in aged rats.

The aging effects on circadian rhythms have diverse implications including changes in the pattern of rhythmic expressions, such as a wide fragmentation of the rhythm of rest-activity and decrease in amplitude of activity regulated by the suprachiasmatic nucleus (SCN). The study of blue light on biological aspects has received great current interest due, among some aspects, to its positive effects on psychiatric disorders in humans. This study aims to evaluate the effect of blue light therapy on the SCN functional aspects, through the evaluation of the rest-activity rhythm, in aging rats. For this, 33 sixteen-months-old male Wistar rats underwent continuous records of locomotor activity and were exposed to periods of 6 hours of blue light during the first half of the light phase (Zeitgeber times 0-6) for 14 days. After this, the rats were maintained at 12h:12h light:dark cycle to check the long-term effect of blue light for 14 days. Blue light repeated exposure showed positive effects on the rhythmic variables of locomotor activity in aged rats, particularly the increase in amplitude, elevation of rhythmic robustness, phase advance in acrophase, and greater consolidation of the resting phase. This effect depends on the presence of daily blue light exposure. In conclusion, our results indicate that blue light is a reliable therapy to reduce circadian dysfunctions in aged rats, but other studies assessing how blue light modulates the neural components to modulate this response are still needed.

The Arousal-Related "Central Thalamus" Stimulation Site Simultaneously Innervates Multiple High-Level Frontal and Parietal Areas.

In human and nonhuman primates, deep brain stimulation applied at or near the internal medullary lamina of the thalamus [a region referred to as "central thalamus," (CT)], but not at nearby thalamic sites, elicits major changes in the level of consciousness, even in some minimally conscious brain-damaged patients. The mechanisms behind these effects remain mysterious, as the connections of CT had not been specifically mapped in primates. In marmoset monkeys (Callithrix jacchus) of both sexes, we labeled the axons originating from each of the various CT neuronal populations and analyzed their arborization patterns in the cerebral cortex and striatum. We report that, together, these CT populations innervate an array of high-level frontal, posterior parietal, and cingulate cortical areas. Some populations simultaneously target the frontal, parietal, and cingulate cortices, while others predominantly target the dorsal striatum. Our data indicate that CT stimulation can simultaneously engage a heterogeneous set of projection systems that, together, target the key nodes of the attention, executive control, and working-memory networks of the brain. Increased functional connectivity in these networks has been previously described as a signature of consciousness.SIGNIFICANCE STATEMENT In human and nonhuman primates, deep brain stimulation at a specific site near the internal medullary lamina of the thalamus ["central thalamus," (CT)] had been shown to restore arousal and awareness in anesthetized animals, as well as in some brain-damaged patients. The mechanisms behind these effects remain mysterious, as CT connections remain poorly defined in primates. In marmoset monkeys, we mapped with sensitive axon-labeling methods the pathways originated from CT. Our data indicate that stimulation applied in CT can simultaneously engage a heterogeneous set of projection systems that, together, target several key nodes of the attention, executive control, and working-memory networks of the brain. Increased functional connectivity in these networks has been previously described as a signature of consciousness.

Retinorecipient areas in the common marmoset (Callithrix jacchus): An image-forming and non-image forming circuitry.

The mammalian retina captures a multitude of diverse features from the external environment and conveys them via the optic nerve to a myriad of retinorecipient nuclei. Understanding how retinal signals act in distinct brain functions is one of the most central and established goals of neuroscience. Using the common marmoset (Callithrix jacchus), a monkey from Northeastern Brazil, as an animal model for parsing how retinal innervation works in the brain, started decades ago due to their marmoset's small bodies, rapid reproduction rate, and brain features. In the course of that research, a large amount of new and sophisticated neuroanatomical techniques was developed and employed to explain retinal connectivity. As a consequence, image and non-image-forming regions, functions, and pathways, as well as retinal cell types were described. Image-forming circuits give rise directly to vision, while the non-image-forming territories support circadian physiological processes, although part of their functional significance is uncertain. Here, we reviewed the current state of knowledge concerning retinal circuitry in marmosets from neuroanatomical investigations. We have also highlighted the aspects of marmoset retinal circuitry that remain obscure, in addition, to identify what further research is needed to better understand the connections and functions of retinorecipient structures.

Effect of senescence on the tyrosine hydroxylase and S100B immunoreactivity in the nigrostriatal pathway of the rat.

Senescence is a natural and progressive physiological event that leads to a series of morphophysiological alterations in the organism. The brain is the most vulnerable organ to both structural and functional changes during this process. Dopamine is a key neurotransmitter for the proper functioning of the brain, directly involved in circuitries related with emotions, learning, motivation and reward. One of the main dopamine- producing nuclei is the substantia nigra pars compacta (SNpc), which establish connections with the striatum forming the so-called nigrostriatal pathway. S100B is a calcium binding protein mainly expressed by astrocytes, involved in both intracellular and extracellular processes, and whose expression is increased following injury in the nervous tissue, being a useful marker in altered status of central nervous system. The present study aimed to analyze the impact of senescence on the cells immunoreactive for tyrosine hydroxylase (TH) and S100B along the nigrostriatal pathway of the rat. Our results show an decreased expression of S100B+ cells in SNpc. In addition, there was a significant decrease in TH immunoreactivity in both projection fibers and TH+ cell bodies. In the striatum, a decrease in TH immunoreactivity was also observed, as well as an enlargement of the white matter bundles. Our findings point out that senescence is related to the anatomical and neurochemical changes observed throughout the nigrostriatal pathway.

Aging Alters Daily and Regional Calretinin Neuronal Expression in the Rat Non-image Forming Visual Thalamus.

Aging affects the overall physiology, including the image-forming and non-image forming visual systems. Among the components of the latter, the thalamic retinorecipient inter-geniculate leaflet (IGL) and ventral lateral geniculate (vLGN) nucleus conveys light information to subcortical regions, adjusting visuomotor, and circadian functions. It is noteworthy that several visual related cells, such as neuronal subpopulations in the IGL and vLGN are neurochemically characterized by the presence of calcium binding proteins. Calretinin (CR), a representative of such proteins, denotes region-specificity in a temporal manner by variable day-night expression. In parallel, age-related brain dysfunction and neurodegeneration are associated with abnormal intracellular concentrations of calcium. Here, we investigated whether daily changes in the number of CR neurons are a feature of the aged IGL and vLGN in rats. To this end, we perfused rats, ranging from 3 to 24 months of age, within distinct phases of the day, namely zeitgeber times (ZTs). Then, we evaluated CR immunolabeling through design-based stereological cell estimation. We observed distinct daily rhythms of CR expression in the IGL and in both the retinorecipient (vLGNe) and non-retinorecipient (vLGNi) portions of the vLGN. In the ZT 6, the middle of the light phase, the CR cells are reduced with aging in the IGL and vLGNe. In the ZT 12, the transition between light to dark, an age-related CR loss was found in all nuclei. While CR expression predominates in specific spatial domains of vLGN, age-related changes appear not to be restricted at particular portions. No alterations were found in the dark/light transition or in the middle of the dark phase, ZTs 0, and 18, respectively. These results are relevant in the understanding of how aging shifts the phenotype of visual related cells at topographically organized channels of visuomotor and circadian processing.

Aging-related changes on social synchronization of circadian activity rhythm in a diurnal primate (Callithrix jacchus).

The input of environmental time cues and expression of circadian activity rhythms may change with aging. Among nonphotic zeitgebers, social cues from conspecific vocalizations may contribute to the stability and survival of individuals of social species, such as nonhuman primates. We evaluated aging-related changes on social synchronization of the circadian activity rhythm (CAR) in a social diurnal primate, the common marmoset. The activity of 18 male marmosets was recorded by actiwatches in two conditions. (1) Experimental - 4 young adult (5 ± 2 yrs of age) and 4 older (10 ± 2 yrs of age) animals maintained under LD 12/12 h and LL in a room with full insulation for light but only partial insulation for sound from vocalizations of conspecifics maintained outdoors in the colony; and (2) Control - 10 young adult animals maintained outdoors in the colony (5 animals as a control per age group). In LL, the CAR of young adults showed more stable synchronization with controls. Among the aged marmosets, two free-ran with τ > 24 h, whereas the other two showed relative coordination during the first 30 days in LL, but free-ran thereafter. These differences were reflected in the "social" phase angles (ψon and ψoff ) between rhythms of experimental and control animal groups. Moreover, the activity patterns of aged animals showed lower social synchrony with controls compared to young adults, with the time lags of the time series between each experimental group and control group being negative in aged and positive in young adult animals (t-test, p < 0.05). The index of stability of the CAR showed no differences according to age, while the intradaily variability of the CAR was higher in the aged animals during LD-resynchronization, who took additional days to resynchronize. Thus, the social modulation on CAR may vary with age in marmosets. In the aged group, there was a lower effect of social synchronization, which may be associated with aging-related changes in the synchronization and generation of the CAR as well as in system outputs.

Astragaloside IV Supplementation Promotes A Neuroprotective Effect in Experimental Models of Neurological Disorders: A Systematic Review.

BACKGROUND: Neurological disorders constitute a growing worldwide concern due to the progressive aging of the population and the risky behavior they represent. Herbal medicines have scientific relevance in the treatment of these pathologies. One of these substances, Astragaloside IV (AS-IV), is the main active compound present in the root of Astragalus membranaceus (Fisch.) Bge, a Chinese medicinal herb with neuroprotective properties. OBJECTIVE: In the present study we performed a systematic review that sought to comprehend the neuroprotective effect presented by AS-IV in experimental models of neurological disorders. METHODS: This study is a systematic review, where an electronic search in United States National Library of Medicine (PubMed), Science Direct, Cochrane Library, Scientific Electronic Library Online (SciELO), Scopus, Web of Science, Medline via Proquest and Periodicos Capes databases covering the years between 2007 and 2017, using "Astragaloside IV" and "Neurodegenerative diseases"; "Astragaloside IV" and " Neurological disorders" as reference terms was made. RESULTS: A total of 16 articles were identified, in which the efficacy of AS-IV was described in experimental models of Parkinson's disease, Alzheimer's disease, cerebral ischemia and autoimmune encephalomyelitis, by improving motor deficits and/or neurochemical activity, especially antioxidant systems, reducing inflammation and oxidative stress. CONCLUSION: The findings of the present study indicate that the administration of AS-IV can improve behavioral and neurochemical deficits largely due to its antioxidant, antiapoptotic and antiinflammatory properties, emerging as an alternative therapeutic approach for the treatment of neurological disorders.

Retinofugal Projections Into Visual Brain Structures in the Bat Artibeus planirostris: A CTb Study.

A well-developed visual system can provide significant sensory information to guide motor behavior, especially in fruit-eating bats, which usually use echolocation to navigate at high speed through cluttered environments during foraging. Relatively few studies have been performed to elucidate the organization of the visual system in bats. The present work provides an extensive morphological description of the retinal projections in the subcortical visual nuclei in the flat-faced fruit-eating bat (Artibeus planirostris) using anterograde transport of the eye-injected cholera toxin B subunit (CTb), followed by morphometrical and stereological analyses. Regarding the cytoarchitecture, the dorsal lateral geniculate nucleus (dLGN) was homogeneous, with no evident lamination. However, the retinal projection contained two layers that had significantly different marking intensities and a massive contralateral input. The superior colliculus (SC) was identified as a laminar structure composed of seven layers, and the retinal input was only observed on the contralateral side, targeting two most superficial layers. The medial pretectal nucleus (MPT), olivary pretectal nucleus (OPT), anterior pretectal nucleus (APT), posterior pretectal nucleus (PPT) and nucleus of the optic tract (NOT) were comprised the pretectal nuclear complex (PNT). Only the APT lacked a retinal input, which was predominantly contralateral in all other nuclei. Our results showed the morphometrical and stereological features of a bat species for the first time.

The Suprachiasmatic Nucleus and the Intergeniculate Leaflet of the Flat-Faced Fruit-Eating Bat (Artibeus planirostris): Retinal Projections and Neurochemical Anatomy.

In mammals, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) are the main components of the circadian timing system. The SCN, classically known as the master circadian clock, generates rhythms and synchronizes them to environmental cues. The IGL is a key structure that modulates SCN activity. Strategies on the use of time by animals can provide important clues about how some species are adapted to competitive process in nature. Few studies have provided information about temporal niche in bats with special attention on the neural substrate underlies circadian rhythms. The aim of this study was to investigate these circadian centers with respect to their cytoarchitecture, chemical content and retinal projections in the flat-faced fruit-eating bat (Artibeus planirostris), a chiropteran endemic to South America. Unlike other species of phyllostomid bats, the flat-faced fruit-eating bat's peak of activity occurs 5 h after sunset. This raises several questions about the structure and function of the SCN and IGL in this species. We carried out a mapping of the retinal projections and cytoarchitectural study of the nuclei using qualitative and quantitative approaches. Based on relative optical density findings, the SCN and IGL of the flat-faced fruit-eating bat receive bilaterally symmetric retinal innervation. The SCN contains vasopressin (VP) and vasoactive intestinal polypeptide (VIP) neurons with neuropeptide Y (NPY), serotonin (5-HT) and glutamic acid decarboxylase (GAD) immunopositive fibers/terminals and is marked by intense glial fibrillary acidic protein (GFAP) immunoreactivity. The IGL contains NPY perikarya as well as GAD and 5-HT immunopositive terminals and is characterized by dense GFAP immunostaining. In addition, stereological tools were combined with Nissl stained sections to estimate the volumes of the circadian centers. Taken together, the present results in the flat-faced fruit-eating bat reveal some differences compared to other bat species which might explain the divergence in the hourly activity among bats in order to reduce the competitive potential and resource partitioning in nature.

Spontaneously Hypertensive Rats (SHR) Are Resistant to a Reserpine-Induced Progressive Model of Parkinson's Disease: Differences in Motor Behavior, Tyrosine Hydroxylase and α-Synuclein Expression.

Reserpine is an irreversible inhibitor of vesicular monoamine transporter-2 (VMAT2) used to study Parkinson's disease (PD) and screening for antiparkinsonian treatments in rodents. Recently, the repeated treatment with a low-dose of reserpine was proposed as a progressive model of PD. Rats under this treatment show progressive catalepsy behavior, oral movements and spontaneous motor activity decrement. In parallel, compared to Wistar rats, spontaneously hypertensive rats (SHR) are resistant to acute reserpine-induced oral dyskinesia. We aimed to assess whether SHR would present differential susceptibility to repeated reserpine-induced deficits in the progressive model of PD. Male Wistar and SHR rats were administered 15 subcutaneously (s.c.) injections of reserpine (0.1 mg/kg) or vehicle, every other day and motor activity was assessed by the catalepsy, oral movements and open field tests. Only reserpine-treated Wistar rats presented increased latency to step down in the catalepsy test and impaired spontaneous activity in the open field. On the other hand, there was an increase in oral movements in both reserpine-treated strains, although with reduced magnitude and latency to instauration in SHR. After a 15-day withdrawn period, both strains recovered from motor impairment, but SHR animals expressed reduced latencies to reach control levels. Finally, we performed immunohistochemistry for tyrosine hydroxylase (TH) and α-synuclein (α-syn) 48 h after the last injection or 15 days after withdrawn. Reserpine-treated animals presented a reduction in TH and an increase in α-syn immunoreactivity in the substantia nigra and dorsal striatum (dSTR), which were both recovered after 15 days of withdraw. Furthermore, SHR rats were resistant to reserpine-induced TH decrement in the substantia nigra, and presented reduced immunoreactivity to α-syn in the dSTR relative to Wistar rats, irrespective of treatment. This effect was accompanied by increase of malondaldhyde (MDA) in the striatum of reserpine-treated Wistar rats, while SHR presented reduced MDA in both control and reserpine conditions relative to Wistar strain. In conclusion, the current results show that SHR are resilient to motor and neurochemical impairments induced by the repeated low-dose reserpine protocol. These findings indicate that the neurochemical, molecular and genetic differences in the SHR strain are potential relevant targets to the study of susceptibility to PD.

Nuclear organization of the substantia nigra, ventral tegmental area and retrorubral field of the common marmoset (Callithrix jacchus): A cytoarchitectonic and TH-immunohistochemistry study.

It is widely known that the catecholamine group is formed by dopamine, noradrenaline and adrenaline. Its synthesis is regulated by the enzyme called tyrosine hydroxylase. 3-hydroxytyramine/dopamine (DA) is a precursor of noradrenaline and adrenaline synthesis and acts as a neurotransmitter in the central nervous system. The three main nuclei, being the retrorubral field (A8 group), the substantia nigra pars compacta (A9 group) and the ventral tegmental area (A10 group), are arranged in the die-mesencephalic portion and are involved in three complex circuitries - the mesostriatal, mesolimbic and mesocortical pathways. These pathways are involved in behavioral manifestations, motricity, learning, reward and also in pathological conditions such as Parkinson's disease and schizophrenia. The aim of this study was to perform a morphological analysis of the A8, A9 and A10 groups in the common marmoset (Callithrix jacchus - a neotropical primate), whose morphological and functional characteristics support its suitability for use in biomedical research. Coronal sections of the marmoset brain were submitted to Nissl staining and TH-immunohistochemistry. The morphology of the neurons made it possible to subdivide the A10 group into seven distinct regions: interfascicular nucleus, raphe rostral linear nucleus and raphe caudal linear nucleus in the middle line; paranigral and parainterfascicular nucleus in the middle zone; the rostral portion of the ventral tegmental area nucleus and parabrachial pigmented nucleus located in the dorsolateral portion of the mesencephalic tegmentum. The A9 group was divided into four regions: substantia nigra compacta dorsal and ventral tiers; substantia nigra compacta lateral and medial clusters. No subdivisions were made for the A8 group. These results reveal that A8, A9 and A10 are phylogenetically stable across species. As such, further studies concerning such divisions are necessary in order to evaluate the occurrence of subdivisions that express DA in other primate species, with the aim of characterizing its functional relevance.

Age-related changes in neurochemical components and retinal projections of rat intergeniculate leaflet.

Aging leads to several anatomical and functional deficits in circadian timing system. In previous works, we observed morphological alterations with age in hypothalamic suprachiasmatic nuclei, one central component of this system. However, there are few data regarding aging effects on other central components of this system, such as thalamic intergeniculate leaflet (IGL). In this context, we studied possible age-related alterations in neurochemical components and retinal projections of rat IGL. For this goal, young (3 months), adult (13 months), and aged (23 months) Wistar rats were submitted to an intraocular injection of neural tracer, cholera toxin subunit b (CTb), 5 days before a tissue fixation process by paraformaldehyde perfusion. Optical density measurements and cell count were performed at digital pictures of brain tissue slices processed by immunostaining for glutamic acid decarboxylase (GAD), enkephalin (ENK), neuropeptide Y (NPY) and CTb, characteristic markers of IGL and its retinal terminals. We found a significant age-related loss in NPY immunoreactive neurons, but not in immunoreactivity to GAD and ENK. We also found a decline of retinal projections to IGL with age. We conclude aging impairs both a photic environmental clue afferent to IGL and a neurochemical expression which has an important modulatory circadian function, providing strong anatomical correlates to functional deficits of the aged biological clock.

Morphological changes in the suprachiasmatic nucleus of aging female marmosets (Callithrix jacchus).

The suprachiasmatic nuclei (SCN) are pointed to as the mammals central circadian pacemaker. Aged animals show internal time disruption possibly caused by morphological and neurochemical changes in SCN components. Some studies reported changes of neuronal cells and neuroglia in the SCN of rats and nonhuman primates during aging. The effects of senescence on morphological aspects in SCN are important for understanding some alterations in biological rhythms expression. Therefore, our aim was to perform a comparative study of the morphological aspects of SCN in adult and aged female marmoset. Morphometric analysis of SCN was performed using Nissl staining, NeuN-IR, GFAP-IR, and CB-IR. A significant decrease in the SCN cells staining with Nissl, NeuN, and CB were observed in aged female marmosets compared to adults, while a significant increase in glial cells was found in aged marmosets, thus suggesting compensatory process due to neuronal loss evoked by aging.

Changes in the suprachiasmatic nucleus during aging: implications for biological rhythms

Animals have neural structures that allow them to anticipate environmental changes and then regulate physiological and behavioral functions in response to these alterations. The suprachiasmatic nucleus of the hypothalamus (SCN) is the main circadian pacemaker in many mammalian species. This structure synchronizes the biological rhythm based on photic information that is transmitted to the SCN through the retinohypothalamic tract. The aging process changes the structural complexity of the nervous system, from individual nerve cells to global changes, including the atrophy of total gray matter. Aged animals show internal time disruptions caused by morphological and neurochemical changes in SCN components. The effects of aging on circadian rhythm range from effects on simple physiological functions to effects on complex cognitive performance, including many psychiatric disorders that influence the well-being of the elderly. In this review, we summarize the effects of aging on morphological, neurochemical, and circadian rhythmic functions coordinated by the main circadian pacemaker, the SCN...

Cognitive, motor and tyrosine hydroxylase temporal impairment in a model of parkinsonism induced by reserpine.

Studies have suggested that cognitive deficits can precede motor alterations in Parkinson's disease (PD). However, in general, classic animal models are based on severe motor impairment after one single administration of neurotoxins, and thereby do not express the progressive nature of the pathology. A previous study showed that the repeated administration with a low dose (0.1mg/kg) of the monoamine depleting agent reserpine induces a gradual appearance of motor signs of pharmacological parkinsonism in rats. Here, we showed this repeated treatment with reserpine induced a memory impairment (evaluated by the novel object recognition task) before the gradual appearance of the motor signs. Additionally, these alterations were accompanied by decreased tyrosine hydroxylase (TH) striatal levels and reduced number of TH+ cells in substantia nigra pars compacta (SNpc). After 30 days without treatment, reserpine-treated animals showed normal levels of striatal TH, partial recovery of TH+ cells in SNpc, recovery of motor function, but not reversal of the memory impairment. Furthermore, the motor alterations were statistically correlated with decreased TH levels (GD, CA1, PFC and DS) and number of TH+ cells (SNpc and VTA) in the brain. Thus, we extended previous results showing that the gradual appearance of motor impairment induced by repeated treatment with a low dose of reserpine is preceded by short-term memory impairment, as well as accompanied by neurochemical alterations compatible with the pathology of PD.

Changes in the suprachiasmatic nucleus during aging: implications for biological rhythms

Animals have neural structures that allow them to anticipate environmental changes and then regulate physiological and behavioral functions in response to these alterations. The suprachiasmatic nucleus of the hypothalamus (SCN) is the main circadian pacemaker in many mammalian species. This structure synchronizes the biological rhythm based on photic information that is transmitted to the SCN through the retinohypothalamic tract. The aging process changes the structural complexity of the nervous system, from individual nerve cells to global changes, including the atrophy of total gray matter. Aged animals show internal time disruptions caused by morphological and neurochemical changes in SCN components. The effects of aging on circadian rhythm range from effects on simple physiological functions to effects on complex cognitive performance, including many psychiatric disorders that influence the well-being of the elderly. In this review, we summarize the effects of aging on morphological, neurochemical, and circadian rhythmic functions coordinated by the main circadian pacemaker, the SCN.(AU)

Nuclear organization of the serotonergic system in the brain of the rock cavy (Kerodon rupestris).

Serotonin, or 5-hydroxytryptamine (5-HT), is a substance found in many tissues of the body, including as a neurotransmitter in the nervous system, where it can exert different post-synaptic actions. Inside the neuro-axis, 5-HT neurons are almost entirely restricted to the raphe nuclei of the brainstem. As such, 5-HT-immunoreactivity has been considered a marker of the raphe nuclei, which are located in the brainstem, at or near the midline. The present study investigated distribution of serotonergic neurons in the brain of the rock cavy (Kerodon rupestris), a rodent species inhabiting the Brazilian Northeast. The cytoarchitectonic location of serotonergic neurons was established through a series of 5-HT immunostained sections, compared with diagrams obtained from adjacent coronal and sagittal sections stained by the Nissl method. The following nuclei were defined: the rostral group, consisting of rostral linear raphe, caudal linear raphe, median and paramedian raphe, dorsal raphe, and pontine raphe nuclei, and the caudal group composed of raphe magnus, raphe pallidus and raphe obscurus nuclei. Other serotonergic neuronal clusters, such as the supralemniscal group and the rostral and caudal ventrolateral medulla oblongata clusters, were found outside the midline. Rare 5-HT-producing neurons were identified in the lateral parabrachial nucleus and in the pontine reticular formation, mostly along fibers of the lateral lemniscus. Despite exhibiting some specializations, the picture outlined for serotonergic groups in the rock cavy brain is comparable to that described for other mammalian species.

Retinal projections and neurochemical characterization of the pregeniculate nucleus of the common marmoset (Callithrix jacchus).

In mammals, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) are the main components of the circadian timing system. The SCN is the site of the endogenous biological clock that generates rhythms and synchronizes them to environmental cues. The IGL is a key structure that modulates SCN activity and is responsible for the transmission of non-photic information to the SCN, thus participating in the integration between photic and non-photic stimuli. Both the SCN and IGL receive projections of retinal ganglion cells and the IGL is connected to the SCN through the geniculohypothalamic tract. Little is known about these structures in the primate brain and the pregeniculate nucleus (PGN) has been suggested to be the primate equivalent of the rodent IGL. The aim of this study was to characterize the PGN of a primate, the common marmoset (Callithrix jacchus), and to analyze its retinal afferents. Here, the marmoset PGN was found to be organized into three subsectors based on neuronal size, pattern of retinal projections, and the distribution of neuropeptide Y-, GAD-, serotonin-, enkephalin- and substance P-labeled terminals. This pattern indicates that the marmoset PGN is equivalent to the IGL. This detailed description contributes to the understanding of the circadian timing system in this primate species considering the importance of the IGL within the context of circadian regulation.

5-HT(1B) receptor in the suprachiasmatic nucleus of the common marmoset (Callithrix jacchus).

Serotonin (5-HT) is involved in the fine adjustments at several brain centers including the core of the mammal circadian timing system (CTS) and the hypothalamic suprachiasmatic nucleus (SCN). The SCN receives massive serotonergic projections from the midbrain raphe nuclei, whose inputs are described in rats as ramifying at its ventral portion overlapping the retinohypothalamic and geniculohypothalamic fibers. In the SCN, the 5-HT actions are reported as being primarily mediated by the 5-HT1 type receptor with noted emphasis for 5-HT(1B) subtype, supposedly modulating the retinal input in a presynaptic way. In this study in a New World primate species, the common marmoset (Callithrix jacchus), we showed the 5-HT(1B) receptor distribution at the dorsal SCN concurrent with a distinctive location of 5-HT-immunoreactive fibers. This finding addresses to a new discussion on the regulation and synchronization of the circadian rhythms in recent primates.