bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of CD4+ and CD8+ T‐cells in the induction of oral tolerance to Actinomyces viscosus in mice
Authors: Sosroseno W. , Bird P. S. , Gemmell E. , Seymour G. J.
Published: April 2006

Mucosal presentation of Actinomyces viscosus results in the induction of antigen specific systemic suppressor cells in mice. The aim of the present study was to determine the phenotype of the suppressor cells responsible for the induction of oral tolerance to low doses of A. viscosus. When CD8 cell‐depleted DBA/2 mice were intragastrically immunized and systemically immunized with A. viscosus, the delayed type hypersensitivity response was suppressed but not the levels of antigen specific serum antibodies. Adoptive transfer of orally tolerized CD4+ cells to CD4+‐depleted mice resulted in suppression of delayed type hypersensitivity response but not of the levels of antigen specific serum antibodies. In contrast, adoptive transfer of orally immunized CD8+ cells to CD8+‐depleted mice resulted in partially suppressed delayed type hypersensitivity response but significantly inhibited the levels of antigen specific serum antibodies. When orally tolerized CD8+ cells were cocultured with systemically immunized CD8+ cell‐depleted spleen cells, splenic specific antibodies were inhibited. However, no suppression of splenic specific antibodies could be observed in the cultures containing orally tolerized CD4+ cells and systemically immunized CD4+ cell‐depleted spleen cells. The results of the present study suggest that oral tolerance of humoral and cellular immunity induced by low doses of A. viscosus may be mediated by CD8+ and CD4+ cells, respectively.
In vitro evaluation of virulence attributes of Candida spp. isolated from patients affected by diabetes mellitus
Authors: Manfredi M. , McCullough M. J. , Al‐Karaawi Z. M. , Vescovi P. , Porter S. R.
Published: April 2006

Background:  Diabetes mellitus is a common disease found worldwide and it has been previously suggested that oral candidal infections may be more frequent or severe in patients with this disease. Systemic and local factors may influence the balance between the host and yeasts, and favour the transformation of Candida isolates from commensal to pathogenic microorganisms. Candida species have developed specific virulence mechanisms that confer the ability to colonise host surfaces, to invade deeper host tissue, or to evade host defences. Few studies have investigated the expression of the virulence attributes of oral Candida isolates in patients with diabetes mellitus.

Material and methods: The in vitro extracellular proteinase production and the in vitro ability to adhere to fibronectin of 229 Candida isolates of two geographic different groups of patients with diabetes mellitus and of healthy subjects were assessed.

Results:  Candida isolates of patients with diabetes mellitus expressed a higher ability to adhere than those of healthy subjects. Higher levels of adhesion were also recorded in patients with a lower oral Candida colonisation. No differences were observed in the in vitro expression of extracellular proteinase of Candida isolates of patients with diabetes mellitus and those of non‐diabetic subjects. Isolates of patients with type 2 diabetes mellitus expressed greater levels of proteinase than isolates of type 1 diabetes mellitus.

Conclusions:  Diabetes mellitus could be considered as an additional variable that may influence not only oral Candida carriage but also the ability of isolates to enhance the expression of virulence attributes.
Cytomegalovirus infection of the liver transplant: virological, histological, immunological, and clinical observations
Authors: Lautenschlager I. , Halme L. , Höckerstedt K. , Krogerus L. , Taskinen E.
Published: April 2006

Abstract: The most common organ‐specific manifestation of cytomegalovirus (CMV) infection after liver transplantation is hepatitis. Here we retrospectively describe the detailed virological, histological, immunological, and clinical findings associated with CMV infection in 229 consecutive adult liver transplantation patients. CMV infection was diagnosed by pp65 antigenemia. From 439 liver biopsies, CMV antigens were demonstrated by immunohistochemistry and CMV DNA by hybridization. The Banff criteria were used for histology. The expression of various adhesion molecules (intercellular adhesion molecule‐1 [ICAM‐1], vascular cell adhesion molecule‐1 [VCAM‐1], endothelial leukocyte adhesion molecule‐1 [ELAM‐1]), their ligands (leukocyte function antigen‐1 [LFA‐1], very late antigen‐4 [VLA‐4], Sialyl‐LewisX‐molecule [SLeX]), and lymphoid activation markers (major histocompatibility complex [MHC] Class II, interleukin‐2‐receptor [IL‐2R]) was demonstrated by immunohistochemistry.

CMV infection of the transplant occurred in 26 patients (11% of all 229 patients and 17% of the 151 patients with liver biopsy). The incidence was higher among seronegative (26%) than in seropositive recipients (9%), but most cases 18/26 (70%) were reactivations. The CMV pp65 antigenemia levels were usually high in primary infections (893±1069, range 50–3000 pp65+cells), but varied widely in reactivations (388±740, range 3–3000). The histological Banff score was slightly increased (2.3±0.9). Microabscesses, lymphocytic infiltration, Kupffer cell reaction, and parenchymal alterations were common but viral inclusions rare. CMV significantly (P<0.05) increased ICAM‐1 and VCAM‐1 expression and the number of LFA‐1, VLA‐4, and Class II‐positive lymphocytes in the graft. All CMV infections were successfully treated with antivirals. Intragraft CMV infection had no influence on the long‐term outcome, but biliary complications were common.

In conclusion, CMV infection of the liver transplant occurred both in primary infection and in reactivation, and also in the cases with low pp65 antigenemia levels. Microabscesses and other histological alterations were common but viral inclusions rare. Increased adhesion molecule expression was associated with lymphocyte infiltration. Successfully treated CMV hepatitis had no influence on the long‐term clinical outcome.
Rejection rates in a randomised trial of tacrolimus monotherapy versus triple therapy in liver transplant recipients with hepatitis C virus cirrhosis
Authors: Samonakis D.N. , Mela M. , Quaglia A. , Triantos C.K. , Thalheimer U. , Leandro G. , Pesci A. , Raimondo M.L. , Dhillon A.P. , Rolles K. , Davidson B.R. , Patch D.W. , Burroughs A.K.
Published: April 2006

Abstract: Background. Reducing immunosuppression not only reduces complications but also may lessen recurrent hepatitis C virus (HCV) infection after liver transplantation.

Patients/Methods. HCV‐infected cirrhotic patients randomised to tacrolimus monotherapy (MT) or triple therapy (TT) using tacrolimus 0.1 mg/kg/day, azathioprine 1 mg/kg/day, and prednisolone 20 mg/day, tapering over 3 months.

Results. Twenty‐seven patients (MT) and 29 (TT) – median follow up 661 days (range, 1–1603). Rejection episodes (protocol/further biopsies) within first 3 months and use of empirical treatment were evaluated. New rejection was diagnosed if repeat biopsy (5‐day interval) did not show improvement. Treated rejection episodes: 20 MT (15 biopsy‐proven) vs. 24 TT (21 biopsy‐proven), with 19 (MT) vs. 24 (TT) methylprednisolone boluses. Overall: 35 episodes (MT) and 46 (TT). Fewer MT patients had histological rejection (70%) than TT patients (86%), with fewer episodes of rejection (18.5% vs. 10%), and more moderate rejection (22% vs. 41%). The MT group had higher early tacrolimus levels. Rates of renal dysfunction, retransplantation, and death were not significantly different.

Conclusion. Tacrolimus monotherapy is a viable immunosuppressive strategy in HCV‐infected liver transplant recipients.
cGMP‐Producing, Atrial Natriuretic Factor‐Responding Cells in the Rat Brain
Authors: de Vente J. , Bol J. G. J. M. , Steinbusch H. W. M.
Published: April 2006

Using an in vitro incubation method, we stimulated cGMP production in rat brain slices by rat ANF‐(103–126). The localization of the cells responding to this ANF stimulation with an increase in cGMP production was studied by cGMP immunocytochemistry. ANF‐responding cells were found in specific loci throughout the central nervous system of the rat. Regions containing the highest number of these cells were: the olfactory bulb, the lateral septum, the bed nucleus of the accessory olfactory tract, the mediobasal amygdala, the central grey area, the medial vestibular nucleus, and the nucleus of the solitary tract. Scattered ANF‐responding, cGMP‐immunoreactive cells were found in the hippocampus, the cingulate cortex, the ventral pallidum, the medial preoptic area, and the endopeduncular nucleus. ANF‐responding cells in these areas had the same morphology, that is, multipolar with numerous processes. The nature of these ANF‐responding cells was studied by sequential staining with an antiserum against glial fibrillary acidic protein (GFAP). In the hippocampus it was demonstrated that all ANF‐responding cells are astroglial cells. However, not all astroglial cells in this area showed a cGMP response, demonstrating a regional heterogeneity. ANF‐responding cells, having the appearance of neuronal cell bodies, could be found in the subfornical organ, and the hypothalamic paraventricular nucleus. Fibres producing cGMP immunoreactivity in response to ANF were found in the median preoptic nucleus, the medial preoptic area, and the dorsal hypothalamus.
Performance of Decorticated Rats on Fixed Interval and Fixed Time Schedules
Authors: Jaldow Eli J. , Oakley David A. , Davey Graham C. L.
Published: April 2006

Rats with neocortex totally removed (decorticates), rats with hippocampal lesions (hippocampals), and their surgical controls, were trained on a fixed interval (FI) 40 s schedule, where the first bar‐press response made more than 40 s after a previous reinforcement was rewarded. The decorticates and hippocampals adopted similar patterns of behaviour to the control groups though there were between‐group differences in the details of performance. Compared to controls the hippocampals showed shorter post‐reinforcement pauses and faster overall rates of responding, whilst the reverse was true of the decorticates. Some of this performance difference in the decorticates was attributed to difficulty in retrieving and consuming solid food reinforcement. The performance of the decorticates and hippocampals, as reflected by the post‐reinforcement pause, response distribution and running rate as a function of post‐reinforcement pause duration, suggests that timing remains operational in both groups. The differences in response profiles between the two experimental groups, however, indicate that hippocampus and neocortex probably make independent contributions to performance in this situation. The decorticates and their control group were later transferred from the FI to a response‐independent fixed time (FT) 40 s schedule. Both groups then returned to the former FI 40 s schedule. The decorticates adjusted their behaviour to the different schedules in the same way as the control animals. The results overall are consistent with previous findings that decortication does not abolish normal patterns of operant learning and extends them to include temporal schedules.
A G Protein Mediates the Inhibition of the Voltage‐Dependent Potassium M Current by Muscarine, LHRH, Substance P and UTP in Bullfrog Sympathetic Neurons
Authors: Lopez H. S. , Adams P. R.
Published: April 2006

The involvement of G proteins in the transduction mechanism of M current (Im) inhibition by extracellular ligands in bullfrog sympathetic neurons was examined using the hydrolysis resistant nucleotide analogues GTPγS and GDPβS. Im was recorded in large (40–60 μm) isolated neurons using the patch‐clamp technique in the whole‐cell configuration, as well as in neurons from the intact ganglion impaled with conventional microelectrodes. In whole‐cell recordings Im could be recorded without significant loss for 1 h or more provided ATP was present in the patch pipette. Muscarine, D‐Ala6‐LHRH, substance P and UTP reversibly inhibited Im in isolated control neurons, with full and rapid recovery of the current following agonist washout. Dialysis of isolated neurons with various concentrations of GTPγS (1–100 μM) affected, in a dose‐dependent manner, the recovery of Im after its inhibition by brief agonist application. With 50 μM GTPμS, Im inhibition became completely irreversible. Similarly, the reversibility of Im inhibition by muscarine was reduced or abolished by the iontophoretic injection of GTPμS through a second microelectrode into neurons of the intact ganglion. GTPμS by itself caused a slow, agonist‐independent suppression of Im in dialysed neurons, thus mimicking agonist action. Dialysis of isolated neurons with GDPβS (100—500 μM) attenuated by half or more the magnitude of Im inhibition by agonist as compared to control neurons. In addition, GDPβS attenuated the response of a given neuron to muscarine and D‐Ala6‐LHRH, and caused slow increase of Im, as a function of dialysis time. Incubation (2–72 h, 4–36°C) of isolated neurons or intact ganglions with activated pertussis toxin had no effect on the response to muscarine. Toxin injections to experimental animals were equally ineffective. In contrast to Im, the additional inward current with increase in conductance induced by muscarine and D‐Ala6‐LHRH reversed with agonist washout in GTPγS‐dialysed neurons, although more slowly than in control neurons. The results in this study indicate that a G protein, possibly pertussis toxin‐insensitive, provides a common coupling step linking muscarinic, substance P, D‐Ala6‐LHRH and UTP receptors to the inhibition of M current.
Rostral Cerebellum Originates from the Caudal Portion of the So‐Called ‘Mesencephalic’ Vesicle: A Study Using Chick/Quail Chimeras
Authors: Martinez Salvador , Alvarado‐Mallart Rosa‐Magda
Published: April 2006

Homotopic and isochronic transplantations of the right dorsal half of the mesencephalic vesicle have been performed between chick and quail embryos at the stage of 10–14 somites. Analysis of the extension of the graft, by means of the quail nucleolar marker, combined with cytoarchitectonic analysis has disclosed that the transplanted neuroepithelium gives rise to isthmic nuclei and to a portion of rostral cerebellum, in addition to the optic tectum and mesencephalic dorsal grisea. These results show that the rostral portion of the cerebellar primordium is located in the so‐called ‘mesencephalic’ alar plate, thus considerably more rostrally than previously supposed. This has been confirmed by two other types of chimeric embryos resulting from homotopic transplantation of either: (i) the quail right alar plate of the first rhombencephalic vesicle, which gives rise to caudal but not rostral cerebellum in the operated side, or (ii) the right alar portion of a segment of the quail neural tube including both the caudal third of the mesencephalic vesicle and the rostral half of the first rhombencephalic vesicle, which gives rise to the whole hemicerebellum in the operated side. Moreover, in chimeric embryos with transplants restricted to the mesencephalic alar plate, the grafted portion of the cerebellar primordium gives rise both to deep cerebellar neurons and to all types of cortical neurons. Among the quail cortical neurons, the Purkinje cells, although intermingled with host Purkinje cells, are organized, at E18, in a characteristic longitudinal band which is strongly reminiscent of the longitudinal functional and morphological organization of the cerebellum. Other types of quail cortical neurons, that is, Golgi cells, granule cells, and molecular layer interneurons, are also observed within this sagittal band. In addition, quail granule cells and molecular layer interneurons as well as quail glial cells, extend over a larger territory on both sides of the longitudinal band containing quail Purkinje cells and even cross the midline and invade the contralateral hemicerebellum. In all types of chimeric embryos, the proliferation, migration, and differentiation of quail transplanted neurons, both in the isthmic region and in the cerebellum, evolve asynchronously from the host homologous ones, following a more precocious and faster developmental schedule. This asynchrony in the development of grafted and host isthmic and cerebellar homologous areas confirms and extends previous findings concerning the proliferation and migration of quail tectal cells in chick quail chimeric embryos (Senut and Alvarado‐Mallart, 1987).
The Effect of Inhibiting the Calcium Activated Neutral Protease, on Motor Unit Size after Partial Denervation of the Rat Soleus Muscle
Authors: Vrbová G. , Fisher T. J.
Published: April 2006

Rat soleus muscles were partially denervated by removal of the L5 ventral ramus at either 4 ‐ 6 days or 17 ‐ 19 days. Local application of leupeptin, a potent inhibitor of the calcium activated neutral protease to these operated muscles, resulted in a significantly greater maximal tetanic tension and motor unit size, when compared to untreated partially denervated muscles. This was achieved in the 4 ‐ 6 day operated animals by an increased number of terminals and in the 17 ‐ 19 day old animals by increased number of axonal sprouts that maintain contact with muscle fibres. In both groups of operated animals in the leupeptin treated muscles large numbers of motor units were able to maintain or achieve an expanded territory, whilst the size of the largest motor unit did not appear to be increased.

It is proposed that leupeptin exerts its effect by inhibiting the degradative action of the neuronal calcium activated neutral protease on the axonal cytoskeleton. Such inhibition may act to prevent or decrease the degradation of cytoskeletal structures in the nerve terminal, and so provide protection for weak terminals at a synapse and growth cones of sprouting axons following partial denervation.
Is the Capacity for Optic Nerve Regeneration Related to Continued Retinal Ganglion Cell Production in the Frog?
Authors: Taylor J. S. H. , Jack J. L. , Easter S. S.
Published: April 2006

In the central nervous system of fish and frogs, some, but not all, axons can regenerate. Retinal ganglion cells are among those that can. The retinae of fish and frogs produce new retinal neurons, including ganglion cells, for months or years after hatching. We have evaluated the hypothesis that retinal axonal regeneration is obligatorily linked to continued production of new ganglion cells.

We used bromodeoxyuridine immunocytochemistry to assess retinal neurogenesis in juvenile, yearling, and 10 year old Xenopus laevis. Retinal ganglion cell genesis was vigorous in the marginal retina of the juveniles, but in the yearlings and the 10 year olds, no new ganglion cells were produced there. Cellular proliferation in the central retina was evident at all three ages, but none of the cells produced centrally were in the ganglion cell layer.

Regeneration was examined in vivo by cutting one optic nerve and then, weeks later, injecting the eye with tritiated proline. Autoradiographs of brain sections showed that the optic nerves of all three ages regenerated. Regeneration in vitro was assessed using retinal explants from frogs of all three ages. In all cases, the cultures produced neurites, with some age‐specific differences in the patterns of outgrowth.

We conclude that retinal axonal regeneration is not linked obligatorily to maintained neurogenesis.
Saccadic Eye Movements and Gaze Holding in the Head‐Restrained Pigmented Rat
Authors: Chelazzi L. , Rossi F. , Tempia F. , Ghirardi M. , Strata P.
Published: April 2006

Spontaneous saccadic eye movements were recorded in seven head‐restrained pigmented rats by means of a phase detection search coil system, both in the light and in the dark. In an illuminated environment, all the rats made numerous spontaneous saccades with an average amplitude of 13.2 deg (±2.2 SD) and a maximal amplitude of 35 deg. In the dark, mean saccadic amplitude was significantly reduced to 9.2 deg (±2.0 SD).

Saccadic peak velocity increased linearly as a function of saccadic size, with no saturation at high amplitude values. In the light, peak velocity increase was 32.7 deg/s/deg (±3.5 SD). This value is higher than that described in many other species including man and is similar to that of the monkey. Also saccadic duration increased linearly as a function of size at a rate of 1 ms/deg, which is closer to that of monkey than to that of other species including man. Both peak velocity and duration were not significantly different in the dark from those measured in the light.

In the light, following a saccadic gaze shift, the rats were able to maintain a steady eye position for long periods, also at large orbital eccentricities. In the dark, on the contrary, the eye presented a drift towards the central position in the orbit. Such a drift had an exponential‐like time course with a time constant of 1567 ms (±829 SD), a value which is much shorter than that of cat and primates. This indicates that in the absence of a visual input, the rat has a poor gaze holding ability compared to other species.
Organotypic Co‐Cultures of Rat Locus Coeruleus and Hippocampus
Authors: Knöpfel T. , Rietschin L. , Gähwiler B. H.
Published: April 2006

Slices from the brainstem at the level of the locus coeruleus and from the hippocampus of 5–7 day old rats were co‐cultured using the roller tube technique. After 2–6 weeks in vitro the co‐cultures were examined with antibodies raised against tyrosine‐hydroxylase (TH). The cultures derived from the brainstem consistently contained a bilateral cluster of TH‐positive neurons with 3–5 long slender dendrites. These neurons typically gave rise to several fine varicose fibres reminiscent of catecholaminergic axons. A morphologically distinct group of TH‐positive neurons was detected in the hippocampal slices. The vast majority of them were located in the subicular region and a smaller number in the CA1/CA3 region of the hippocampal explant. TH‐positive neurons were also present in mono‐cultures of hippocampus or brainstem.

In the vast majority of co‐cultures, a variable number of TH‐immunoreactive fibres of neurons derived from the locus coeruleus grew over considerable distances to terminate finally within the co‐cultured hippocampus where they branched to form a diffuse innervation plexus with club‐like endings. Even after several weeks in vitro, TH‐positive fibres could still be seen exploring sites which were not related to their target, including the cell‐free areas surrounding the cultures. Fibres in these outgrowth areas formed whirl‐like endings. TH‐positive fibres arising from neurons located in the hippocampus, on the other hand, did not branch extensively and never projected over long distances.

Nerve growth factor had no apparent trophic effect on TH‐positive cells in the hippocampus, the locus coeruleus, or in the co‐cultures.
Intrinsic Organization and Connectivity of Intrastriatal Striatal Transplants in Rats as Revealed by DARPP‐32 Immunohistochemistry: Specificity of Connections with the Lesioned Host Brain
Authors: Wictorin K. , Ouimet C. C. , Björklund A.
Published: April 2006

Intrastriatal grafts of tissue obtained from the striatal or neocortical primordia of rat fetuses have been studied with respect to their intrinsic organization and connectivity using antibodies to DARPP‐32 in combination with acetylcholinesterase (AChE) histochemistry, tyrosine hydroxylase (TH) immunocytochemistry, and anterograde and retrograde axonal tracing techniques. The striatal grafts were characterized by distinct patches of DARPP‐32‐immunoreactive neurons, which were identical to the densely AChE‐positive patches stained in adjacent sections from the same specimens. The non‐patch areas possessed only few DARPP‐32‐positive neurons and contained only sparse AChE‐positive fibres. The cortical grafts, by contrast, contained no neurons with clear‐cut DARPP‐32‐positivity and they exhibited a sparse, evenly distributed AChE fibre network, similar to that seen in the non‐patch areas of the striatal grafts.

The host dopaminergic afferents, as revealed by TH immunostaining, had grown selectively into the DARPP‐32‐positive patches in the striatal grafts, where they formed a dense terminal network around the DARPP‐32‐positive cell bodies. The non‐patch areas, as well as the cortical grafts, received only sparse TH innervation. By contrast, the host cortical afferents, labelled by Phaseolus vulgaris leucoagglutinin from the host frontal cortex, were seen to extend into both the patch and non‐patch areas of the striatal grafts.

Transplant neurons projecting into the host brain were labelled by Fluoro‐Gold injections into the ipsilateral host globus pallidus. These injections labelled large numbers of medium‐sized neurons within the striatal grafts and the vast majority of them (over 85%) were confined to the DARPP‐32‐positive patches. Similar Fluoro‐Gold injections labelled only few graft neurons in the cortical grafts.

The results indicate that the striatal grafts are composed of a mixture of striatal and non‐striatal tissue, and that the striatal graft compartment selectively establishes afferent and efferent connections with the host nigro‐pallidal system. These graft connections demonstrate a remarkable specificity in the formation of graft–host connectivity. The results, moreover, suggest that developmental properties of the grafted striatal primordium are retained and expressed in the implanted cell suspension, and that the neuronal systems of the lesioned adult host brain, at least to some extent, remain responsive to growth regulating mechanisms normally operating during ontogenetic development.
Changes in Regional Cerebral Oxidative Metabolism Induced by Tactile Learning and Recognition in Man
Authors: Roland Per E. , Eriksson Lars , Widén Lennart , Stone‐Elander Sharon
Published: April 2006

We measured the regional cerebral oxidative metabolism (rCMRO2) with positron emission tomography in normal healthy volunteers in three different stages: rest, tactile learning, and tactile recognition of complicated geometrical objects. The frequency of manipulatory movements during tactile recognition was twice that of tactile learning. Tactile recognition with the right hand increased rCMRO2 in six prefrontal cortical areas, bilaterally in the supplementary motor areas, the premotor areas and supplementary sensory areas, in the left primary motor and primary sensory area, in the left anterior superior parietal lobule, bilaterally in the secondary somatosensory area, the anterior insula, lingual gyri, hippocampus, basal ganglia, anterior parasagittal cerebellum, and lobus posterior cerebelli. These structures have in other studies been found to participate in manipulatory movements and analysis of somatosensory information. Tactile learning increased rCMRO2 in the same structures as did tactile recognition. Thus we found no differences in the anatomical structures participating in storage and retrieval. However the rCMRO2 increases in the left premotor cortex, supplementary motor area, and left somatosensory hand area were larger during tactile recognition in accordance with the higher frequency of manipulatory movements and higher flux of somatosensory information from the periphery during recognition. Despite this the rCMRO2 was significantly higher in the neocerebellar cortex during tactile learning. Since there were no learning effects on the manipulatory movements, this extra metabolic activity in the lateral cerebellum was attributed to energy demanding processes associated with climbing fibre activity during storage of somatosensory information.
Hunger Modulates the Responses to Gustatory Stimuli of Single Neurons in the Caudolateral Orbitofrontal Cortex of the Macaque Monkey
Authors: Rolls Edmund T. , Sienkiewicz Zenon J. , Yaxley Simon
Published: April 2006

In order to determine whether the responsiveness of neurons in the caudolateral orbitofrontal cortex (a secondary cortical gustatory area) is influenced by hunger, the activity evoked by prototypical taste stimuli (glucose, NaCl, HCl, and quinine hydrochloride) and fruit juice was recorded in single neurons in this cortical area before, while, and after cynomolgous macaque monkeys were fed to satiety with glucose or fruit juice.

It was found that the responses of the neurons to the taste of the glucose decreased to zero while the monkey ate it to satiety during the course of which his behaviour turned from avid acceptance to active rejection.

This modulation of responsiveness of the gustatory responses of the neurons to satiety was not due to peripheral adaptation in the gustatory system or to altered efficacy of gustatory stimulation after satiety was reached, because modulation of neuronal responsiveness by satiety was not seen at earlier stages of the gustatory system, including the nucleus of the solitary tract, the frontal opercular taste cortex, and the insular taste cortex.

The decreases in the responsiveness of the neurons were relatively specific to the food with which the monkey had been fed to satiety. For example, in seven experiments in which the monkey was fed glucose solution, neuronal responsiveness decreased to the taste of the glucose but not to the taste of blackcurrant juice. Conversely, in two experiments in which the monkey was fed to satiety with fruit juice, the responses of the neurons decreased to fruit juice but not to glucose.

These and earlier findings lead to a proposed neurophysiological mechanism for sensory‐specific satiety in which the information coded by single neurons in the gustatory system becomes more specific through the processing stages consisting of the nucleus of the solitary tract, the taste thalamus, and the frontal opercular and insular taste primary taste cortices, until neuronal responses become relatively specific for the food tasted in the caudolateral orbitofrontal cortex (secondary) taste area. Then sensory‐specific satiety occurs because in this caudolateral orbitofrontal cortex taste area (but not earlier in the taste system) it is a property of the synapses that repeated stimulation results in a decreased neuronal response.

Evidence was obtained that gustatory processing involved in thirst also becomes interfaced to motivation in the caudolateral orbitofrontal cortex taste projection area, in that neuronal responses here to water were decreased to zero while water was drunk until satiety was produced.
Demonstration of a Mamillo‐Ponto‐Cerebellar Pathway
Authors: Aas Jan‐Erik , Brodal Per
Published: April 2006

The pathway from the mamillary complex to the cerebellum via the pontine nuclei has been studied using several anterograde and retrograde tracing techniques in the cat. We have also compared the pontine terminal regions of fibres from the mamillary complex and from the cingulate gyrus.

Implantations of crystalline horseradish peroxidase wheat germ agglutinin (HRP‐WGA) in the mamillary complex and lesions of the cingulate gyrus were combined in the same animal with injections of HRP‐WGA, rhodamine‐B‐isothiocyanate (RITC), and Fluoro‐Gold in different parts of the cerebellar hemisphere.

Fibres from both the mamillary complex and the cingulate gyrus terminate mainly within a transversely oriented, c‐shaped band in the ipsilateral, rostral pontine nuclei. Within this band the terminal fields of fibres from the mamillary complex and the cingulate gyrus form a mosaic‐like pattern of partly overlapping patches. Pontine regions receiving a mamillary input project mainly to the ventral paraflocculus, and to a lesser degree to the dorsal paraflocculus, but apparently not to the uvula or crus II. Judging from the literature it seems highly unlikely that other parts of the cerebellar hemispheres receive projections from these pontine regions. Fibres from the ventral paraflocculus were shown to terminate in the parvicellular part of the lateral cerebellar nucleus only.

The present findings would seem to imply that inputs from the mamillary complex and a related cortical region, the cingulate gyrus, are partly integrated, partly kept separate at the precerebellar level. This would ensure that small groups of cells in the rostral pontine nuclei receive a specific set of afferents. Conceivably, the information transmitted to the cerebellum by these groups of pontine cells might be related to functions of the mamillary complex, such as learning, motivation, and spatial memory.
Noradrenaline‐ and Enkephalin‐Induced Inhibition of Voltage‐Sensitive Calcium Currents in NG108‐15 Hybrid Cells
Authors: McFadzean I. , Docherty R. J.
Published: April 2006

Voltage‐sensitive calcium currents were recorded from chemically differentiated neuroblastoma × glioma hybrid (NG108‐15) cells using the whole‐cell clamp technique. Both noradrenaline and [D‐Ala2, D‐Leu5] enkephalin (DADLE) reversibly depressed the amplitude of the calcium current by up to 30%. The response to noradrenaline occluded that to DADLE suggesting that both agonists depress the same fraction of current. The response to DADLE but not that to noradrenaline desensitized rapidly. Cells responded normally to noradrenaline when desensitized to the opioid. Responses to either agonist were absent in cells pre‐incubated with pertussis toxin. In addition the response to noradrenaline became irreversible in cells dialysed internally with a non‐hydrolysable analogue of GTP. The response to noradrenaline was not affected by treatment of the cells with either membrane‐permeable analogues of cAMP or a combination of forskolin and isobutylmethylxanthine. It is concluded that both noradrenaline and DADLE depress the same fraction of voltage‐dependent calcium current in NG108‐15 cells; that the responses are mediated by a pertussis‐sensitive GTP‐binding protein but are not secondary to a reduction in the intracellular concentration of cAMP; and that desensitization of the opioid response occurs at a site linked intimately to the opioid receptor rather than at a common site in the transduction pathway between receptor activation and reduction in the calcium channel current.
Oxytocin Neurotransmission in the A1‐area of the Brainstem Induces Hormonal Vasopressin Release in Rats
Authors: Hermes Michael L. H. J. , Buijs Ruud M. , van Heerikhuize Joop J. , van den Born Jaap , van der Woude Tjitske P.
Published: April 2006

To investigate the role of the oxytocin innervation of the caudal ventrolateral medulla, immunocytochemical techniques were used to demonstrate the presence of oxytocin fibres and terminals in close apposition to noradrenergic neurons of the A1‐area.

Subsequently, in freely moving animals fitted with an indwelling jugular venous catheter and a bilaterally implanted chronic cannula in the A1‐area, it was examined whether infusions of oxytocin in this area were able to influence hormonal vasopressin release. It appeared that nanomolar (50–500 nM) concentrations of oxytocin induce a fourfold rise in plasma vasopressin values. The specificity of this effect was established with control infusions of Ringer, vasopressin, and the addition of an antagonist to oxytocin. It was not possible to demonstrate a major role for oxytocin in the A1‐area in the release of hormonal vasopressin occurring during haemorrhage.

These data permit us to conclude that oxytocin acts on presumably noradrenergic neurons of the A1‐area leading to the release of vasopressin into the peripheral circulation. The circumstances under which oxytocin is released in this area remain to be established.
Hippocampal Noradrenaline and Serotonin Release over 24 Hours as Measured by the Dialysis Technique in Freely Moving Rats: Correlation to Behavioural Activity State, Effect of Handling and Tail‐Pinch
Authors: Kalén Peter , Rosegren Evald , Lindvall Olle , Björklund Anders
Published: April 2006

Hippocampal extracellular levels of noradrenaline (NA), 5‐hydroxytryptamine (5‐HT), and 5‐hydroxyindole‐acetic acid (5‐HIAA) were monitored with the microdialysis technique in freely moving rats. In one experiment 30 min samples were collected during 24 h of continuous perfusion, and the monoamine output was compared to the behavioural activity state, as arbitrarily classified in three categories: sleep/rest, drowsiness and full alertness associated with complex behaviours. In the individual animal the hippocampal NA and 5‐HT output showed pronounced fluctuations during the 24 h period, but the 30 min sampling times did not allow for a clear‐cut correlation to behavioural activity state. However, the mean NA and 5‐HT output for all animals during the dark period of the day was 43 and 38% higher, respectively, than during the light period, and the average NA and 5‐HT levels in samples collected during periods of high behavioural activity was 34 and 45% higher, respectively, than during periods of rest or sleep. In contrast, there were no detectable changes in extracellular 5‐HIAA. The selective serotonin uptake blocker indalpine, added to the perfusion fluid at 1 μM, increased the extracellular 5‐HT levels 6‐fold, with a similar correlation to behavioural activity state as without indalpine.

In a second experiment the effect of handling and tail‐pinch was studied in 15 min sample fractions. Gentle handling of the animals during the sampling period increased the hippocampal NA and 5‐HT output by 32 and 72%, respectively, and a similar increase (63 and 48%) was obtained by application of tail‐pinch. Maximum NA output was reached during the handling or tail‐pinch period, whereas maximal 5‐HT levels were detected in the subsequent 15 min sample fraction. No changes in extracellular 5‐HIAA was observed.

It is concluded (1) that intracerebral microdialysis provides a useful method for the study of extracellular NA and 5‐HT in the hippocampal formation of conscious rats during active behaviour; (2) that there are substantial fluctuations in hippocampal NA and 5‐HT output in freely moving rats which correlate with the light‐dark cycle as well as with the activity state of the animals; (3) that the spontaneous variations in 5‐HT output are maintained during reuptake blockade; and (4) that behavioural activation through gentle handling or tail‐pinch elicits NA and 5‐HT release. The present data support a role of the forebrain NA and 5‐HT systems in behavioural state control and highlights the necessity of experimental designs in which the spontaneous fluctuations in transmitter release are controlled for in studies of, for example, drug effects on NA and 5‐HT release in conscious animals.
Dependence of Retinogeniculate Transmission on Membrane Voltage in the Cat
Authors: Lo Fu‐Sun , Sherman S. Murray
Published: April 2006

The mammalian lateral geniculate nucleus seems organized to gate or control the gain of retino‐geniculate transmission, the result of which is then relayed to the visual cortex. We have performed in vivo intracellular studies of retinogeniculate transmission along these retino‐geniculo‐cortical pathways in cats by recording the retinally evoked excitatory postsynaptic potential (EPSP) in geniculate neurons. In cats, these pathways are organized into two parallel and functionally distinct channels, the X and Y pathways. We found that nearly all geniculate X cells display a fairly conventional voltage dependency for their retinally evoked EPSPs, because the amplitudes of these EPSPs decrease fairly linearly with membrane depolarization as the EPSP reversal potential is approached. Rare X cells and all Y cells, however, show an unconventional response: over a wide range of membrane potentials, their EPSP amplitudes increase with membrane depolarization. This increase does not result from alterations in neuronal input resistance and instead seems due to changes in synaptic conductance. The underlying cause of this voltage dependency remains to be determined. None the less, it does afford an interesting means by which retinogeniculate transmission can be gated, since non‐retinal inputs (e.g. corticogeniculate axons) that can control a relay Y cell's membrane potential can also modulate the cell's EPSP amplitude.
Differential Calcium Binding Protein Immunoreactivity Distinguishes Classes of Relay Neurons in Monkey Thalamic Nuclei
Authors: Jones E. G. , Hendry S. H. C.
Published: April 2006

The distributions of neurons displaying immunoreactivity for two calcium binding proteins, parvalbumin and 28Kd calbindin, were studied in the thalamus of M. fascicularis. Colocalization experiments were carried out to determine the extent to which parvalbumin‐ and calbindin‐like immunoreactivity was found in the same cells and the extent to which either was localized in GABAergic interneurons. Anterograde and retrograde tracing experiments involving the fluorescent tracer, fast blue, were also used to determine that cells expressing the calcium binding proteins projected upon the cerebral cortex.

In the dorsal thalamus, nuclei are distinguished by different patterns of parvalbumin‐like and calbindin‐like immunoreactivity. In certain nuclei, for example the lateral dorsal and anterior pulvinar, neurons express immunoreactivity for only one of the calcium binding proteins. In others, neurons in different layers, for example the dorsal lateral geniculate nucleus, or in different compartments, for example the intralaminar nuclei, express immunoreactivity for either parvalbumin or calbindin; in other nuclei, for example the ventral group, neurons are mixed and immunoreactivity for parvalbumin and calbindin is commonly colocalized. In the ventral thalamus and epithalamus, similar patterns are observed.

Colocalization of parvalbumin‐ and GABA‐immunoreactivity is found in all cells of the reticular nucleus but only in certain cells in selected nuclei of the dorsal thalamus, namely the dorsal lateral geniculate and magnocellular medial geniculate. No calbindin‐positive cells are also GABA‐positive.

Most parvalbumin and/or calbindin positive cells in the dorsal thalamus project to the cerebral cortex, as indicated by the retrograde tracing studies, and many parvalbumin positive fibres entering the cerebral cortex could also be shown to contain fast blue anterogradely transported from a thalamic injection.

Most of the major sensory and motor pathways entering the dorsal thalamus express parvalbumin immunoreactivity. The optic tract also expresses calbindin immunoreactivity but most other calbindin positive fibres entering the thalamus ascend in the midbrain tegmentum.

The differential distributions of parvalbumin and calbindin implied by these results suggest that thalamic cells belonging to different functional systems and projecting differentially upon the cerebral cortex can be distinguished by differential expression of these or closely related calcium binding proteins. This may yield clues to their differential responsivity to afferent driving.
The Organization of Connections between Areas V5 and V1 in Macaque Monkey Visual Cortex
Authors: Shipp S. , Zeki S.
Published: April 2006

Area V5 or MT of primate extrastriate visual cortex is specialized for involvement in the analysis of motion and receives input from two layers, 4B and 6, of the striate cortex or V1. Injections of horseradish peroxidase ‐ wheatgerm agglutinin into V5 reveal a patchy distribution of labelled cells and axonal terminals in layer 4B, suggesting the presence of a segregated and functionally specialized subsystem within the layer. The patches are similar in size and frequency to the cytochrome oxidase blobs of layers 2 and 3, but bear little systematic relationship to them. V5‐efferent cells in layer 6, however, tend to avoid the cores of the blobs.

The back projection from V5 is continuously distributed in layers 6 and 1, though it is absent inside representations of the central 10° in the latter; it is also diffusely distributed between the patches in layer 4B and over a territory wider than that occupied by labelled cells. It is thus inferred that the back projection probably influences (a) V5‐efferent cells other than those projecting to the injected site in V5, and (b) cells projecting to locations other than V5.

There are no major changes in the cortical frequency of V5‐efferent cells with eccentricity in the visual field representation. The V5‐efferent cells of layer 6 are tenfold less frequent than those of layer 4B and as a population may therefore be involved with only a limited sector of directions of movement. Furthermore, their topographic distribution does not always coincide exactly with that of the layer 4B population, as if a site in V5 receives information about slightly non‐corresponding regions of the visual field from the two layers.
The Organization of Connections between Areas V5 and V2 in Macaque Monkey Visual Cortex
Authors: Shipp S. , Zeki S.
Published: April 2006

Area V2 of the cerebral cortex of higher primates has a complex cytochrome oxidase architecture whose most characteristic element is a set of stripes running orthogonal to its long axis. These stripes can be related to the segregation between the various pathways in which V2 participates. In the macaque monkey the more metabolically active stripes are alternately thick and thin and only one set, the thick stripes, is found to possess clusters of labelled cells following injections of horseradish peroxidase — wheatgerm agglutinin into area V5. Some of these clusters, but not all, coincide with substructures inside the thick stripes. V2 of the owl monkey has a similar organization except that the diversification into thick and thin stripes is less prominent, both in terms of their appearance and in that more than every alternate stripe is connected to area MT, the likely homologue of V5.

The return projection from V5 to V2 is more widespread than the origin of the forward projection. It extends not only between the clusters of V5‐efferent cells within the thick stripes but also across the intervening thin stripes and less active interstripes. Because the latter subserve functions different from those of the thick stripes it would seem that their receipt of a back projection from an area to which they do not project, V5, may be relevant to the process of intergration of signals relating to different attributes of vision.
Onset Characteristics of Long‐Term Potentiation in the Guinea‐Pig Hippocampal CA1 Region in Vitro
Authors: Gustafsson B. , Asztely F. , Hanse E. , Wigström H.
Published: April 2006

The temporal development of long‐term potentiation (LTP) was examined in the CA1 region of the hippocampal slice preparation (bath temperature 30°C). LTP was evoked by a single brief afferent tetanus (3–40 impulses at 50 Hz) given in the presence of picrotoxin (to facilitate LTP induction). Short‐lasting potentiation processes unrelated to LTP were excluded by comparing the potentiation obtained in picrotoxin solution with that obtained in normal solution or in the presence of the N‐methyl‐D‐aspartate receptor antagonist 2‐amino‐5‐phosphonovalerate. LTP was also evoked by pairing single test volleys with brief (2–3 impulses) heterosynaptic tetani in picrotoxin solution. Both methods showed no significant rise of LTP until about 3 s after the induction event. LTP thereafter developed almost linearly towards a peak within 20–25 s after the tetanus, the time course being practially independent of the induction method and of the relative amount of LTP evoked. The latency and rise time of LTP depended on bath temperature, being about twice as long at 25°C as at 30°C. Following the peak, LTP rapidly decayed to less than half its peak value in 8 min, the decay tending to be less with longer trains. The LTP component reaching its peak 20–25 s after a tetanus was practically occluded after a saturating homosynaptic tetanization, and was only partially recovered 1 h afterwards. The latency to the onset of LTP suggests an indirect coupling between the calcium influx, presumed to trigger the potentiation, and the expression of LTP. The independence of the early time course with respect to the induction strength indicates that the intervening system(s) operates in a linear manner.