Development of palecortical projections through the anterior commissure of hamsters adopts progressive,not regressive,strategies

The perinatal development of anterior commissure projections was studied in hamsters by use of carbocyanine crystals implanted either into the commissure or into the ventrolateral prosencephalon. The earliest fascicles of growing commissural fibers had reached the midline on day 14 of gestation (E14). On E15, these fibers had entered the opposite hemisphere and reached the borders of their target regions. No waiting period was observed, since on E16 axons were already collateralizing into most targets. On P1, labelled cells were seen in all regions projecting through the anterior commissure in adults, namely, the anterior olfactory nucleus, olfactory tubercle, piriform cortex, nucleus of the lateral olfactory tract, bed nucleus of the stria terminalis, insular, perirhinal, entorhinal, and temporal cortices, as well as the amygdaloid complex. No evidence of topographical exuberance was detected. Counts of labelled neurons showed that the number of commissural cells increased gradually after birth. It is concluded that the development of paleocortical connections through the anterior commissure employs progressive strategies, lacking the regressive phenomena that are characteristic of the neocortical projections through the corpus callosum.     

Development of the anterior commissure in the opossum: Midline extracellular space and glia coincide with early axon decussation

While the anterior commissure has been shown to be an important route of information transfer in the forebrain, relatively little is known about its anatomical development. Glial substrates and extracellular spaces have been associated with the maturation of other large-fiber tracts, such as the corpus callosum and retinofugal pathway. The present study examined early stages in the maturation of the commissure in the gray short-tailed opossum, Monodelphis domestica. Monodelphis offspring are born after a short 14-day gestation, and, unlike in rats and mice, the anterior commissure develops entirely during the postnatal period. A number of techniques were employed: the carbocyanine dye Dil was used to label early axons in the region, semithin plastic sections were used to examine the extracellular environment of the developing commissure, and immunocytochemistry for glial fibrillary acidic protein (GFAP) was used to characterize glial components. Results suggest that the first commissural fibers that cross the midline pass through a region of large extracellular spaces and may use GFAP-immunoreactive cells and processes as guides during their midline decussation. © 1997 John Wiley & Sons, Inc. J Neurobiol 32: 403–414, 1997.     

Dual functional activity of semaphorin 3B is required for positioning the anterior commissure

Chemorepulsion by semaphorins plays a critical role during the development of neuronal projections. Although semaphorin-induced chemoattraction has been reported in vitro, the contribution of this activity to axon pathfinding is still unclear. Using genetic and culture models, we provide evidence that both attraction and repulsion by Sema3B, a secreted semaphorin, are critical for the positioning of a major brain commissural projection, the anterior commissure (AC). NrCAM, an immunoglobulin superfamily adhesion molecule of the L1 subfamily, associates with neuropilin-2 and is a component of a receptor complex for Sema3B and Sema3F. Finally, we show that activation of the FAK/Src signaling cascade distinguishes Sema3B-mediated attractive from repulsive axonal responses of neurons forming the AC, revealing a mechanism underlying the dual activity of this guidance cue.     

EphB1 and EphB2 intracellular domains regulate the formation of the corpus callosum and anterior commissure

The two cortical hemispheres of the mammalian forebrain are interconnected by major white matter tracts, including the corpus callosum (CC) and the posterior branch of the anterior commissure (ACp), that bridge the telencephalic midline. We show here that the intracellular signaling domains of the EphB1 and EphB2 receptors are critical for formation of both the ACp and CC. We observe partial and complete agenesis of the corpus callosum, as well as highly penetrant ACp misprojection phenotypes in truncated EphB1/2 mice that lack intracellular signaling domains. Consistent with the roles for these receptors in formation of the CC and ACp, we detect expression of these receptors in multiple brain regions associated with the formation of these forebrain structures. Taken together, our findings suggest that a combination of forward and reverse EphB1/2 receptor‐mediated signaling contribute to ACp and CC axon guidance. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 405–420, 2016     

Myelogenesis and estimation of the number of axons in the anterior commissure of the chick (Gallus gallus)

Summary By use of light- and electron microscopy the anterior commissure of the chick was studied at different times during development. Between the 19th day of incubation and the 35th day after hatching the cross-sectional area of the anterior commissure, as determined from mid-sagittal sections, undergoes a 6-fold increase in size. Thereafter the area remains fairly constant. The total number of fibres in the anterior commissure was estimated to be 89000. The full complement of fibres is already present by the 19th day of incubation. Myelogenesis occurs mainly between the 19th day of incubation and the 35th day after hatching, concomitant with the increase in cross-sectional area. From the 35th day after hatching, myelinated fibres comprise approximately 40% of the total number of fibres. The median diameter of unmyelinated fibres is about 0.35–0.40 m. The median diameters of myelinated axons and fibres are 0.8–1.0 m and 1.1–1.3 m, respectively.     

Homing pigeons subjected to section of the anterior commissure can build up two olfactory maps in the deflector lofts

Summary Pigeons kept in two cages with screens which deflect the wind clockwise (CW) or counterclockwise (CCW) show corresponding deflections in their initial orientation. In order to determine the nature of this phenomenon, experimental birds were treated as follows: 1. The anterior commissure of the forebrain (AC), which mediates the interhemispheric transfer of olfactory input was sectioned; 2. After surgery, each experimental bird was kept alternately in a CW cage with its right nostril plugged, and in a CCW cage with its left nostril plugged; the two treatments were alternated every 3 days for 69 days before test releases began. In 23 out of 28 cases the experimentals showed CW deflections when released with the right nostril plugged and CCW deflections when released with the left nostril plugged. The controls were intact, and their nostrils were free in each phase of the experiment. They were subdivided into two groups: one group was kept in the CW cage when the experimentals were in the same cage, the other group in the CCW cage when the experimentals stayed there. In the remaining time each group was kept in a fenced loft. The behaviour of controls demonstrated that the time the experimentals had spent in each kind of deflector cage had been long enough to produce the corresponding deflections in initial orientation. Control experiments were then performed on pigeons with the AC sectioned (2 series) and on intact birds (1 series), both maintained in lofts which did not deflect the wind, and released with one nostril plugged. They did not show deflections similar to those of the experimentals. The present results allow to conclude that the deflector loft effect is olfactory in nature, and that the AC sectioned pigeons, alternately subjected to different treatments in deflector cages are able to acquire two different odour maps for navigation.Abbreviations AC anterior commissure of the forebrain sectioned - CCW counterclockwise - CW clockwise     

Circadian locomotor rhythms, but not photoperiodic responses, survive surgical isolation of the SCN in hamsters.

Surgical isolation of the suprachiasmatic nuclei (SCN) within a hypothalamic island is reported to produce loss of circadian rhythmicity. The results have been interpreted to indicate that SCN efferents are necessary for the expression of circadian rhythms. It is not clear, however, whether the loss of circadian rhythms in behavioral responses following SCN isolation is attributable to transection of efferents, to loss of cells within the island, or to gliosis produced by the knife cut. To explore this issue, we examined locomotor activity and gonadal state of male golden hamsters housed in constant darkness (DD, with a dim red light for maintenance) for at least 10 weeks following isolation of the SCN from the rest of the brain by cuts by means of a Halasz wire microknife. Brain sections were immunocytochemically stained for the peptides vasoactive intestinal polypeptide (VIP), vasopressin (VP) or neurophysin II (NP II), and neuropeptide Y (NPY) to localize the SCN and to assess its viability, and for glial fibrillary acidic protein (GFAP) to delimit the border of the knife cut. Experimental animals with VIP and VP/NP II immunoreactivity in the SCN within the island retained free-running locomotor rhythms following transection of SCN efferents. Animals with cuts that failed to sever SCN efferents, and sham-operated animals (in which the Halasz knife was lowered but not rotated), also maintained circadian rhythmicity. Hamsters sustaining severe damage to the SCN showed disrupted locomotor activity. In those hamsters that retained circadian locomotor rhythmicity following SCN isolation, gonads failed to regress in DD, demonstrating the absence of an appropriate photoperiodic response. The results suggest a multiplicity of SCN coupling mechanisms in the control of circadian rhythms.     

Development of projections between areas of the nervous system

A theory of projections in the nervous system (such as the retino-tectal projection) is proposed. Components of axonal growth cones and target tissue interact and cooperate, within the area of contact, to generate a guiding parameter, in the simplest case a guiding substance of distributionp. The components which are involved in this production are assumed to have graded distributions with respect to position in the projecting and target area, respectively. The distributionp thus produced guides the growth cone in the direction of maximal slope until the minimal value ofp is reached. In this way, each growth cone can be guided to a position on the target tissue which depends on the origin of the fiber in such a manner that a projection results. Adhesive forces could but need not be involved in the guiding mechanism. The slope ofp may interfere with an intracellular pattern forming mechanism within the growth cone, determining the polarity of activation (as modelled previously on the basis of autocatalysis and lateral inhibition) and thus the direction of growth. For the generation of a distribution ofp leading to a reliable projection, simple graded distributions in the projecting and target area suffice, involving one or two components in each dimension. Their effect on the generation ofp may be activatory as well as inhibitory. Exponential gradients give rise to particularly simple mapping functions. The following is an example of this general type of model: Growth cones as well as target tissue contribute to the production of a guiding substance. For each dimension, there is, in the target tissue, an exponentially graded component exerting (directly or indirectly) two functions: it actively produces guiding substancep and it interacts, in an inhibitory fashion, with the production ofp by a component of the growth cone (which is, in turn, graded with respect to position of origin in the projecting area). While the theory is proposed as a fair approximation of the primary events in neural projections, superimposed regulatory effects can also be incorporated. These include fiber-fiber interactions, mechanisms smoothing out unequal density distributions of axon terminals and effects of time of arrival of fibers on the projection, which have been proposed previously as primary mechanisms generating projections. A further extension of the model is to assume that crude and more refined positional specificity is determined in a combinatorial fashion, allowing the possibility of interchanges and transformations of parameters.     

Photoperiod alters macrophage responsiveness, but not expression of Toll-like receptors in Siberian hamsters

Defense against pathogens is a critical component of comparative and ecological biology. However, pathogen recognition, a process necessary for the facilitation of systemic immune response, remains understudied in a comparative context, yet could provide insight into how the immune system interacts with pathogens in variable environments. We examined pathogen recognition by macrophages in relation to an ecological variable, day length, in Siberian hamsters (Phodopus sungorus). Because peritoneal macrophages collected in long, summer-like day lengths are more responsive to a lipopolysaccharide (LPS) challenge compared to macrophages collected during short, winter-like day lengths, we hypothesized that these functional differences are mediated by variation in pathogen recognition, which occurs through binding to Toll-like receptors (TLRs). We predicted that expression of TLR2 and 4, the receptors that bind and respond specifically to LPS, would be upregulated in long vs. short days, and that expression of these receptors would reflect macrophage responsiveness to LPS. Macrophages collected during long days were again more responsive to LPS challenge compared to short-day macrophages; however, TLR2 and TLR4 expression was similar between photoperiods and were unrelated to our measure of macrophage responsiveness suggesting that other downstream intracellular mechanisms may be responsible for photoperiod-based variation in macrophage responsiveness in this species.     

Effects of corticotrophin-releasing hormone on corticotrophs in anterior pituitary gland allografts in hypophysectomized,orchidectomized hamsters

Summary We investigated the effects of corticotrophin-releasing hormone (CRH) on the percentage of anterior pituitary gland (APG) cells which are corticotrophs as well as the size and shape of corticotrophs. Pituitary glands were removed from 7-week-old male hamsters and placed beneath the renal capsules of hamsters that had been hypophysectomized and orchidectomized 3 weeks previously. Beginning 6 days after each host had received a single allograft, each was injected subcutaneously twice daily with 4 g CRH or vehicle for 16 days. Six hosts in each group were decapitated 16 h after the last injection. Sections of anterior pituitary tissue were stained for ACTH and with hematoxylin. The percentage of corticotrophs among APG cells was greater in allografts exposed to exogenous CRH (20%) than in allografts exposed to vehicle (15%). Exposure to exogenous CRH increased the cross-sectional area of corticotroph cells in allografts to values greater than those measured for corticotrophs in allografts exposed to vehicle, without altering the shape of cells. Results of subsequent studies suggested that hamsters with allografts injected with vehicle do not release ACTH and that exogenous CRH causes an abrupt release of ACTH from allografts. These results indicate that CRH releases ACTH from ectopic corticotrophs and that administration of CRH can increase corticotroph size and the percentage of APG cells that are corticotrophs.     

Postnatal development of thalamic reticular nucleus projections to the anterior thalamic nuclei in rats

The thalamic reticular nucleus (TRN) projects inhibitory signals to the thalamus, thereby controlling thalamocortical connections. Few studies have examined the development of TRN projections to the anterior thalamic nuclei with regard to axon course and the axon terminal distributions. In the present study, we used parvalbumin (PV) immunostaining to investigate inhibitory projections from the TRN to the thalamus in postnatal (P) 2- to 5-week-old rats (P14–35). The distribution of PV-positive (+) nerve fibers and nerve terminals markedly differed among the anterior thalamic nuclei at P14. Small, beaded nerve terminals were more distributed throughout the anterodorsal nucleus (AD) than in the anteroventral nucleus (AV) and anteromedial nucleus (AM). PV+ fibers traveling from the TRN to the AD were observed in the AV and AM. Nodular nerve terminals, spindle or en passant terminals, were identified on the axons passing through the AV and AM. At P21, axon bundles traveling without nodular terminals were observed, and nerve terminals were distributed throughout the AV and AM similar to the AD. At P28 and P35, the nerve terminals were evenly distributed throughout each nucleus. In addition, DiI tracer injections into the retrosplenial cortex revealed retrogradely-labeled projection neurons in the 3 nuclei at P14. At P14, the AD received abundant projections from the TRN and then projected to the retrosplenial cortex. The AV and AM seem to receive projections with distinct nodular nerve terminals from the TRN and project to the retrosplenial cortex. The projections from TRN to the AV and AM with nodular nerve terminals at P14 are probably developmental-period specific. In comparison, the TRN projections to the AD at P14 might be related to the development of spatial navigation as part of the head orientation system.Key words: Thalamic reticular nucleus, parvalbumin, axon terminal, development, anterior thalamic nucleus, rat     

Effects of growth hormone-releasing hormone on somatotrophs in anterior pituitary gland allografts in hypophysectomized,orchidectomized hamsters

Summary We investigated the influences of growth hormone-releasing hormone (GHRH) on the percentage, size, and shape of somatotrophs in ectopic anterior pituitary tissue. Entire pituitary glands removed from 7-week-old male hamsters were placed beneath the renal capsules of 12-week-old hamsters that had been hypophysectomized and castrated 3 weeks previously. Beginning 6 days after each host had received a single allograft, each was injected subcutaneously twice daily with 4 g GHRH in 100 l of vehicle or 100 l of vehicle for 16 days. Six hosts in each group were killed by decapitation on day 17, 16 h after the last injection. Nine normal male hamsters were also decapitated and their pituitary glands were removed. Sections of anterior pituitary tissue were stained for GH and with hematoxylin. The percentage of anterior pituitary cells that stained for growth hormone was similar in the 3 groups. In contrast, somatotrophs in grafts had a smaller mean cross-sectional area than those observed in glands in situ. This effect was reversed by GHRH. Analysis of the shape of somatotrophs in both groups of grafts disclosed that they were less circular in cross-section than those in glands in situ. The results suggest that GHRH may not play a role in maintaining the percentage of somatotrophs among anterior pituitary cells, but that it does play a role in maintaining their size.     

Self-regulation of the immune system through biobehavioral strategies

Increasing scientific study and attention is being directed to mind-body interactions, particularly to the interrelationships between the brain and the immune system. This effort has created a new interdisciplinary field, psychoneuro-immunology. An overview of this new field is provided, followed by a comprehensive survey of the growing evidence suggesting that measurable immune system parameters can be influenced by biobehavioral strategies involving self-regulation. Modalities included are relaxation and imagery techniques, biofeedback-assisted strategies, the use of humor, and affiliation to influence emotional states, hypnosis, and conditioning paradigms. The majority of studies have reported significant immune parameter changes. Additional well-designed research is needed to clarify and confirm these initial findings. Future research would benefit from investigating the clinical implications of these immune parameter changes. Knowledge of effects of the mind on the body is rapidly expanding and may be important for achieving improved immune system functioning and health.This research was partially supported by the Fetzer Foundation Grant, Stress Management and Immunomodulation the Voluntary Controls Program of the Menninger Foundation, and the Karl Menninger School of Psychiatry.     

Self-regulation of the immune system through biobehavioral strategies

Increasing scientific study and attention is being directed to mind-body interactions, particularly to the interrelationships between the brain and the immune system. This effort has created a new interdisciplinary field, psychoneuroimmunology. An overview of this new field is provided, followed by a comprehensive survey of the growing evidence suggesting that measurable immune system parameters can be influenced by biobehavioral strategies involving self-regulation. Modalities included are relaxation and imagery techniques, biofeedback-assisted strategies, the use of humor, and affiliation to influence emotional states, hypnosis, and conditioning paradigms. The majority of studies have reported significant immune parameter changes. Additional well-designed research is needed to clarify and confirm these initial findings. Future research would benefit from investigating the clinical implications of these immune parameter changes. Knowledge of effects of the mind on the body is rapidly expanding and may be important for achieving improved immune system functioning and health.     

Proteomic profiling for cancer progression: Differential display analysis for the expression of intracellular proteins between regressive and progressive cancer cell lines

Tumor development and progression consist of a series of complex processes involving multiple changes in gene expression (Paolo et al. Physiol. Rev., 1993, 73, 161-195; Lance et al. Cell., 1991, 64, 327-336). Tumor cells acquire an invasive and metastatic phenotype that is the main cause of death for cancer patients. Therefore, for early diagnosis and effective therapeutic intervention, we need to detect the alterations associated with transition from benign to malignant tumor cells on a molecular basis. To unravel alterations concerned with tumor progression, the proteomic approach has attracted great attention because it can identify qualitative and quantitative changes in protein composition, including post-translational modifications. In this study, we performed proteomic differential display analysis for the expression of intracellular proteins in the regressive cancer cell line QR-32 and the inflammatory cell-promoting progressive cancer cell line QRsP-11 of murine fibrosarcoma by two-dimensional gel electrophoresis and mass spectrometry using an Agilent 1100 LC/MSD Trap XCT. We found 11 protein spots whose expression was different between QR-32 and QRsP-11 cells and identified nine proteins, seven of which, calreticulin precursor, tropomyosin 1 alpha chain, annexin A5, heat shock protein (HSP)90-alpha, HSP90-beta, PEBP, and Prx II, were over-expressed, and two, Anp32e and HDGF, which were down-regulated. The results suggest an important complementary role for proteomics in identification of molecular abnormalities in tumor progression.     

Spatial learning in golden hamsters: Relationship between food-searching strategies and difficulty of the task

In an elevated maze consisting of three reconvergent radial arms, golden hamsters were tested with the same experimental rule: to choose each path without repeating any choice. However, variations of procedure concerning (a) the location of the reward in the maze, and (b) reinforcement contingencies, were introduced in order to define several problems involving variable levels of difficulty. The relationship between response strategies and difficulty of the task was then studied. The common learning criterion was the achievement of three consecutive correct daily sessions, each session corresponding to a particular sequence (pattern) of choices of paths. Response strategies were studied by analyzing the patterns obtained over the three final sessions in which an animal reached the learning criterion. Such a set of patterns (triplet) could be heterogeneous (patterns all different), mixed (two identical patterns, one different) or stereotyped (identical patterns). No relationship was found between the mean level of difficulty presented by each learning problem and the occurrence of a particular type of triplet. However, in each situation, mixed triplets were the most frequently recorded and corresponded to the medium individual speeds of learning whereas heterogeneous triplets corresponded to rapid successes and stereotyped triplets to delayed successes. These findings indicate that, whatever the problem designed to be tested in a three-arm maze, the various forms of solutions reflect different individual adaptative mechanisms.