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Biomedical subjects

A Gasbarri

Publications and source records attributed to A Gasbarri.

At least 19 recordsLinked to original sources

Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions.

BACKGROUND: Thyroid cancer is the most common endocrine malignant disease, but preoperative diagnosis remains a challenge. Fine-needle aspiration cytology has greatly improved the clinical management of thyroid nodules, but the preoperative characterisation of follicular lesions is very difficult. Many patients are thus referred to surgery more for diagnosis than for therapeutic necessity. We undertook an international multicentre study to assess the usefulness of immunohistocytochemical staining for two potential markers of malignant thyrocytes. METHODS: Expression of galectin-3 and CD44v6 was tested on 1009 thyroid lesions (tissue specimens and cytological cell-blocks) and 226 fresh cytological samples obtained preoperatively by ultrasound-guided fine-needle aspiration of thyroid nodules (prospective analysis). The test used monoclonal antibodies specific for CD44v6 and galectin-3, the indirect avidin-biotin complex immunoperoxidase method, and 3-amino-9-ethyl-carbazole as substrate. FINDINGS: The sensitivity, specificity, positive predictive value, and diagnostic accuracy of this test method (for coexpression of the two markers) in the prospective analysis were 88%, 98%, 91%, and 97%, respectively. The sensitivity and specificity of galectin-3 immunodetection alone in discriminating benign from malignant thyroid lesions were more than 99% and 98% respectively, and the positive predictive value and diagnostic accuracy were 92% and 99%. INTERPRETATION: The integration of galectin-3 immunostaining with conventional cytomorphological and clinical diagnostic procedures represents a sensitive and reliable diagnostic approach for preoperative identification of thyroid carcinomas. This test method improves the diagnostic accuracy of conventional cytology and provides the molecular basis for a new nosological assignation of the not yet classified thyroid neoplasms of indeterminate malignant behaviour.

Antigens, Differentiation↗

Structural variability of CD44v molecules and reliability of immunodetection of CD44 isoforms using mAbs specific for CD44 variant exon products.

CD44 can be considered structurally and functionally one of the most variable surface molecules. Alternative splicing of variant exons as well as posttranslational modifications of the molecule (differences in glycosylation) generate a rich repertoire of CD44 isoforms (CD44v), some of which seem to play a key role in tumor growth and progression. Immunodetection of CD44 isoforms in vivo, using mAbs specific for CD44 variant exon products, is largely used to identify those CD44 molecules involved in tumor growth and progression and to interfere with CD44-mediated processes. In the present work we demonstrate that the immunoreactivity of some mAbs directed to CD44 exon-specific epitopes can be impaired by the structural variability of the molecule. Our findings demonstrate that (1) specific exon assortment and/or posttranslational modifications of CD44v molecules can mask CD44 exon-specific epitopes; (2) glycosaminoglycan side chains, carried by some CD44v isoforms of high molecular weight, may play a critical role in determining the exact conformation of the molecule, which is necessary for the detection of CD44 variant epitopes by specific mAbs; and (3) in a panel of stable transfectants expressing CD44 N-glycosylation site-specific mutants, generated in the constant region of CD44 extracellular domain, asparagine-isoleucine substitution is sufficient per se to impair the immunoreactivity of several mAbs to pan-CD44. Thus, conformational changes due to the alternative splicing of CD44 variant exons and/or posttranslational modifications of the molecule (different degree of glycosylation), which are cell type-specific, are likely to generate CD44 variants that elude immunodetection. These findings strongly suggest that immunohistochemical analysis of CD44 expression in vitro and in vivo, using mAbs specific for CD44 variant exon epitopes, can potentially be impaired by a large number of false negative results.

Antibodies, Monoclonal↗

Strain-dependent involvement of D1 and D2 dopamine receptors in muscarinic cholinergic influences on memory storage.

These experiments examined the interaction of muscarinic and dopaminergic systems in influencing memory for one-trial inhibitory avoidance training in mice of the C57BL/6 and DBA/2 strains. In both strains, immediate post-training systemic administration of the muscarinic cholinergic agonist oxotremorine enhanced retention and the cholinergic antagonist atropine impaired retention. No effects were seen with injections 2 h post-training. Furthermore, the drugs did not affect retention performance of animals that received no footshock on the training trial. These results confirm previous findings indicating that muscarinic cholinergic drugs affect memory by influencing memory consolidation. In C57 mice, pretreatment with selective D1 or D2 dopamine (DA) receptor agonists (SKF 38393 or LY 171555, respectively) in otherwise non-effective doses (5 and 0.25 mg/kg, respectively) potentiated the effects of oxotremorine (0.04 mg/kg). Furthermore, in C57 mice pretreatment with selective D1 or D2 receptor antagonists (SCH 23390 or (-)-sulpiride) in otherwise non-effective doses (0.025 and 6 mg/kg, respectively) blocked the memory enhancing effects of oxotremorine. The memory impairing effects of atropine (3 mg/kg) were blocked by the D1 and D2 selective agonists and potentiated by the selective D1 or D2 antagonists. In contrast, in DBA mice, the D1 and D2 selective agonists antagonised the memory enhancing effects of oxotremorine (0.02 mg/kg) and potentiated the effects of atropine (2 mg/kg). Furthermore, the D1 and D2 antagonists potentiated the effects of oxotremorine and antagonised those of atropine. These findings indicate that although muscarinic cholinergic influences on memory storage are comparable in mice of these two strains, the cholinergic-dopaminergic interactions are opposite in the two strains. These results have implications for hypotheses of cholinergic and dopaminergic regulation of memory storage.

Animals↗

Serotonergic input to cholinergic neurons in the substantia innominata and nucleus basalis magnocellularis in the rat.

The aim of the present study was to determine, at the light microscopic level, whether the serotonergic fibers originating from the dorsal raphe nucleus (B7), median raphe nucleus (B8) and ventral tegmentum (B9) make putative synaptic contacts with cholinergic neurons of the nucleus basalis magnocellularis and substantia innominata. For this purpose, we utilized: (i) the anterograde transport of Phaseolus vulgaris leucoagglutinin combined with choline acetyltransferase immunohistochemistry; (ii) choline acetyltransferase/tryptophan hydroxylase double immunohistochemistry; and (iii) the FluoroGold retrograde tracer technique combined with tryptophan hydroxylase immunohistochemistry. Following iontophoretic injections of Phaseolus vulgaris leucoagglutinin in the dorsal raphe nucleus, labeling was observed primarily in the ventral aspects of the nucleus basalis magnocellularis and in the intermediate region of the substantia innominata. When Phaseolus vulgaris leucoagglutinin was combined with choline acetyltransferase immunohistochemistry, a close association between the Phaseolus vulgaris leucoagglutinin-positive fibers and cholinergic neurons was observed, even though the majority of the Phaseolus vulgaris leucoagglutinin-immunoreactive terminals seemed to establish contact with non-cholinergic elements. Following Phaseolus vulgaris leucoagglutinin injection in the median raphe nucleus, very few labeled fibers with no evident close contact with nucleus basalis magnocellularis and substantia innominata cholinergic neurons were observed. After tryptophan hydroxylase/choline acetyltransferase double immunohistochemistry, a plexus of serotonergic (tryptophan hydroxylase-positive) fibers in the vicinity of choline acetyltransferase-immunoreactive neurons of the substantia innominata and nucleus basalis magnocellularis was observed, and some serotonergic terminals have been shown to come into very close contact with the cholinergic cells. Most of the tryptophan hydroxylase-immunoreactive terminals seem to establish contacts with non-cholinergic cells. Following FluoroGold injection in the nucleus basalis magnocellularis and substantia innominata, the majority of retrogradely labeled neurons was observed mainly in the ventromedial cell group of the dorsal raphe nucleus. In this area, a minority of the FluoroGold-positive neurons was tryptophan hydroxylase immunoreactive. These findings show that serotonergic terminals, identified in very close association with the cholinergic neurons in the substantia innominata and nucleus basalis magnocellularis, derive primarily from the B7 serotonergic cell group of the dorsal raphe nucleus, and provide the neuroanatomical evidence for a direct functional interaction between these two neurotransmitter systems in the basal forebrain.

Animals↗

Angiomyofibroblastoma and aggressive angiomyxoma: two benign mesenchymal neoplasms of the female genital tract. An immunohistochemical study.

We describe a rare case of angiomyofibroblastoma (AMF) of the vulva and one case of aggressive angiomyxoma (AAM) of the pelvic region and, with the help of an extensive revision of the literature, we attempt to define their histogenesis and peculiar biological behaviour by an immunohistological evaluation. Our results indicate that AAM, which is characterized by the presence of a high content of glycosaminoglycans in the stroma, expresses uniformly vimentin and hyaluronate receptor CD44, and heterogeneously muscle specific actin (MSA) and desmin, while AMF displays a positive reaction for vimentin, desmin and laminin, and only a weak and heterogeneous positivity for CD44. Both AMF and AAM showed no immunohistochemical reactivity for alpha-smooth muscle actin (ASMA), myoglobin, cytokeratin, collagen type IV, CD68 and S-100. The stromal cells of AAM were negative for laminin. These findings support the suggestion of an origin of the two entities by a common myofibroblastic progenitor, which normally occurs in the lower female genital tract and subsequently undergoes a neoplastic transformation. The expression of CD44 by AAM, which has never been reported before, could be responsible for its more aggressive behaviour, because this receptor is able to mediate migration of neoplastic cells on a hyaluronate rich extracellular matrix. It is speculated that the neoplastic cell of the AAM and AMF of the vulva is a specific myofibroblast which probably arises from undifferentiated mesenchymal cells normally occurring in the lower female genital tract.

Angiofibroma↗

Galectin-3 and CD44v6 isoforms in the preoperative evaluation of thyroid nodules.

PURPOSE: Thyroid cancer is the most frequently occurring endocrine malignancy; however, preoperative diagnosis of some lesions, in particular those with follicular histology, is difficult, and a consistent number of not otherwise-specified "follicular nodules" are surgically resected more for diagnosis than therapeutic purposes. In this study, we investigated whether the lectin-related molecules CD44v6 and galectin-3, the expression of which is altered during deregulated cell growth and malignant transformation, could be potential markers for improving the diagnostic accuracy of conventional cytology. MATERIALS AND METHODS: A comparative immuno-chemical and molecular analysis was performed on 157 thyroid specimens representative of normal, benign, and malignant tissues, and on 36 cytologic samples obtained preoperatively by fine-needle aspiration biopsy from nonselected patients with palpable thyroid nodules. RESULTS: Normal thyrocytes did not express galectin-3 nor CD44v6. Although the expression of CD44v6 isnegligible in thyroiditis, these molecules are variably detected in benign and malignant proliferative lesions. Interestingly, galectin-3 is never expressed in benign lesions, but it is invariably detected in cancers. A comparative evaluation of CD44v6 and galectin-3 expression in thyroid malignancies demonstrated that these molecules are coexpressed at the messenger RNA and protein level in almost all lesions. CONCLUSION: Our findings suggest that CD44v6 and galectin-3 could be potential markers to preoperatively identify malignant transformed thyrocytes. Immunodetection of these molecules on cytologic specimens obtained by fine-needle aspiration biopsy is an accurate and improved method for selecting, on a molecular basis, those nodular lesions of the thyroid gland that need to be surgically resected.

Adenoma↗

The effect of intrastriatal injection of liposome-entrapped tyrosinase on the dopamine levels in the rat brain.

Parkinson's disease is a neurodegenerative disorder which is mainly characterized by degeneration of the dopaminergic cells in the nigro-striatal system. Due to a lowered L-tyrosine 3-monooxygenase activity, L-tyrosine is not sufficiently transformed to L-DOPA. To date the most common therapy is the administration of the dopamine precursor L-DOPA, with severe collateral effects. Therefore, the substitution of the lacking tyrosine hydroxylase with tyrosinase might be a novel therapeutical approach that would generate specifically L-DOPA from L-tyrosine. We present here evidence that stereotaxic injection of liposome-entrapped tyrosinase is able to significatively increase the levels of dopamine in the rat brain. The catecholamines L-DOPA, dopamine, L-epinephrine, L-norepinephrine were extracted by acid treatment from the brains and detected by HPLC.

Animals↗

Oxygen uptake, heart rate and blood lactate concentration during a normal training session of an aerobic dance class.

The aim of this research was to investigate the physiological responses and, in particular, the participation of lactic acid anaerobic metabolism in aerobic dance, which is claimed to be pure aerobic exercise. In contrast to previous studies, that have put subjects in very unfamiliar situations, the parameters were monitored in the familiar context of gymnasium, practice routine and habitual instructor. A group of 30 skilled fairly well-trained women performed their usual routine, a combination of the two styles: low (LI) and high impact (HI), and were continuously monitored for heart rate (HR) and every 8 min for blood lactate concentration ([La-]b). Of the group, 15 were tested to determine their maximal aerobic power (VO2max) using a cycle-ergometer. They were also monitored during the routine for oxygen uptake (VO2) by a light telemetric apparatus. The oxygen pulses of the routine and of the corresponding exercise intensity in the incremental test were not statistically different. The mean values in the exercise session were: peak HR 92.8 (SD 7.8)% of the subject's maximal theoretical value, peak VO2 99.5 (SD 12.4)% of VO2max, maximal [La-]b 6.1 (SD 1.7) mmol x l(-1), and mean 4.8 (SD 1.3) mmol x l(-1). Repeated measures ANOVA found statistically significant differences between the increasing [La-]b values (P < 0.001). In particular, the difference between the [La-]b values at the end of the mainly LI phase and those of the LI-HI combination phase, and the difference between the samples during the combination LI-HI phase were both statistically significant (both P = 0.002 and P = 0.002). The similar oxygen pulses confirmed the validity of the present experiment design and the reliability of HR monitoring in this activity. The HR, VO2 and, above all, the increase of [La-]b to quite high values, showing a non steady state, demonstrated the high metabolic demand made by this activity that involved lactic acid metabolism at a much higher level than expected.

Adult↗

Strain-dependent effects of D2 dopaminergic and muscarinic-cholinergic agonists and antagonists on memory consolidation processes in mice.

The interaction between muscarinic-cholinergic and dopaminergic systems in the modulation of memory storage of Y-maze discrimination (YMD) task was examined in C57BL/6 and DBA/2 strains of mice. In C57BL/6 mice, post-training systemic (i.p.) administration of the D2-agonist quinpirole facilitated retention and the D2-antagonist (-)-sulpiride impaired retention. Opposite effects were observed in DBA/2 strain. The facilitating or impairing effects of quinpirole and (-)-sulpiride were blocked by simultaneous post-training administration of muscarinic-cholinergic agonists and antagonists. The memory enhancing effects of the cholinergic agonist oxotremorine were not blocked by simultaneous administration of sulpiride in C57BL/6 mice or quinpirole in DBA/2 mice. Furthermore, the memory impairing effects of the cholinergic antagonist atropine were not blocked by simultaneous administration of quinpirole in C57BL/6 mice or sulpiride in DBA/2 mice. These findings indicate that the effects of D2-receptor agonists and antagonists on retention of YMD task are strain-dependent and mediated through muscarinic-cholinergic mechanisms.

Animals↗

The dopaminergic mesencephalic projections to the hippocampal formation in the rat.

1. The dopaminergic mesencephalic neurons projecting to the hippocampal formation are distributed in three cell groups: A8 region in the retrorubral field, A9 region in the substantia nigra and A10 region in the ventral tegmental area. 2. Anterograde and retrograde tract-tracing techniques combined with immunohistochemical procedures indicate a topographical organization of mesencephalic dopaminergic projections towards the hippocampal formation. 3. Electrophysiological evidence suggest that dopaminergic mesencephalic neurons could have a regulatory role in suppressing hippocampal excitability. 4. The functional significance of the mesohippocampal dopaminergic system is largely unknown, although it was suggested that this projection could have a role in methamphetamine-produced hypermotility and in modulation of memory processes.

Animals↗

Effects of the retrorubral field stimulation on the excitability of the rat hippocampus in vivo.

We studied in vivo the influences exerted by the retrorubral field (RRF) on the on commissural-evoked CA1 pyramidal cell excitability in the rat hippocampal formation (HF). The stimulation of RRF before the activation of the contralateral CA3 area evoked in all the studied rats a reduction in amplitude of the evoked population spike in the CA1 pyramidal cell body layer of both the dorsal and the ventral HF. No significant differences in the intensity of the inhibitory effect were observed between dorsal and ventral parts of the HF. The stimulation of the ipsilateral RRF reduced the amplitude of the evoked population spike in a higher degree with respect to the contralateral side. Since these side-to-side differences were significant, it can be concluded that the RRF-induced inhibitory effect is stronger on the ipsilateral CA1 pyramidal cells. The inhibitory effect appears within 0.1 s of stimulating the RRF, reaches its maximal effect around 0.4-0.5 s following the conditioning train and returned to its control size after 5 s.

Animals↗

The projections of the retrorubral field A8 to the hippocampal formation in the rat.

The dopaminergic neurons in the midbrain of the rat are located in three groups: the ventral tegmental area (VTA-A10), substantia nigra (SN-A9), and retrorubral field (RRF-A8). We have recently examined the organization of the projections from the VTA and the SN to the hippocampal formation (HF) in the rat. In the present study we characterize the projections of the RRF to the HF by using anterograde tracing, retrograde tracers, and tyrosine hydroxylase (TH) immunohistochemistry. Following iontophoretical injections of Phaseolous vulgaris leucoagglutinin (PHA-L) into the RRF, anterograde labeling was observed primarily in the ipsilateral subiculum and adjacent CA1 cell field. Sparse labeling was also observed in the CA3 cell field and dentate gyrus. The distribution of RRF neurons projecting to the HF was examined by injecting retrograde fluorescent tracers (fluorogold, fast blue, and nuclear yellow) into several hippocampal areas. The retrograde tracer findings indicate that the medial aspects of the RRF project to the subiculum and adjacent CA1 cell field of both the septal and temporal HF. In order to evaluate the percentage of dopaminergic cells of the RRF projecting to the HF, the retrograde neuronal tracer fluorogold was used in combination with TH immunohistochemistry. The quantitative evaluation of retrograde labeled and TH-immunoreactive (IR) cells showed that RRF projections to the HF are partially (10-18%) dopaminergic. The findings suggest that the general pattern of distribution and organization of the RRF-A8 projections to the HF is similar to that observed in our previous studies examining hippocampal afferents from the VTA and SN. The data also suggest a crude topographical organization of RRF afferents to the HF and a more prominent input to the temporal than to the septal HF.

Amidines↗

Spatial memory impairment induced by lesion of the mesohippocampal dopaminergic system in the rat.

The hippocampal formation has long been thought to play a role in learning and memory. Previous studies from our laboratory examined the organization of mesencephalic projections to the hippocampal formation in the rat. In order to evaluate the effects on learning and memory of retrograde selective lesions of mesencephalic dopaminergic neurons, following bilateral injection of 6-hydroxydopamine in the dorsal and ventral subiculum and adjacent CA1 field of the hippocampal formation, young adult Sprague-Dawley rats were trained in classical inhibitory avoidance, inhibitory avoidance using a multiple trial (training to criterion) and the standard Morris water maze task (cued and spatial versions). With regard to inhibitory avoidance, retention was examined one, three and 10 days after training. Concerning the Morris water maze task, 6-hydroxydopamine-lesioned and sham-operated rats received four training trials on each of four days. After training sessions, the rats were tested during a 60-s probe trial (free-swim trial) in which the platform was removed from the maze. The loss of mesencephalic dopaminergic neurons in the 6-hydroxydopamine-lesioned rats, compared to sham-operated rats, was verified by tyrosine hydroxylase immunohistochemistry. Although the 6-hydroxydopamine-lesioned rats were indistinguishable from sham-operated rats in performing the inhibitory avoidance and the cued version of the Morris water maze task, in the spatial version of the Morris water maze, lesioned rats, compared to controls, exhibited significant differences in the latency (P < 0.05), quadrant time (P < 0.01) and number of platform crossings (P < 0.05). These results suggest that the rat's ability to acquire spatial learning and memory for place navigation in the Morris water maze is likely to be dependent also on the integrity of mesohippocampal dopaminergic connections.

Animals↗

Mesolimbic dopaminergic neurons innervating the hippocampal formation in the rat: a combined retrograde tracing and immunohistochemical study.

A major mesolimbic projection towards the hippocampal formation (HF) has been extensively described, but no clear evidence of its dopaminergic content has been demonstrated. In order to evaluate the percentage of dopaminergic (DA) cells of ventral tegmental area (VTA-A10) and adjacent substantia nigra (SN-A9) projecting to the HF, the retrograde neuronal tracer technique was combined with the tyrosine hydroxylase (TH) immunocytochemistry. Fluoro-gold (FG) was injected in several areas (subiculum, CA1, CA3, dentate gyrus) of either septal and temporal HF. Sections containing retrogradely FG labeled neurons were either mounted directly as controls or incubated with TH antiserum and revealed with rhodamine. The quantitative evaluation of retrogradely labeled and TH-IR stained cells showed that both VTA and SN projections towards the HF are partially (15-18%) dopaminergic. Ten percent of the DA neurons of the VTA projected to contralateral HF, whereas none did in the SN. In conclusion, the temporal HF (mainly subiculum and adjacent CA1) appears to receive the main DA afferents from both VTA cells and medial half of SN, pars compacta, whereas the septal HF (particularly CA1) receives its DA input from neurons located in the ventral half and in the upper and lower borders of the VTA.

Animals↗

Anterograde and retrograde tracing of projections from the ventral tegmental area to the hippocampal formation in the rat.

Employing anterograde tracing with Phaseolus vulgaris-leucoagglutinin (PHA-L), and a triple labeling protocol using retrogradely transported fluorescent tracers, we examined the projections from the ventral tegmental area (VTA-A10) to the hippocampal formation (HF) in the rat. Injections of PHA-L into VTA resulted in labeling in the ventral subiculum (stratum oriens and molecular layer) and in the adjacent CA1 field (stratum oriens, pyramidal, suprapyramidal and molecular layers) of HF. Additional labeling was observed in the stratum oriens of CA3 and in the hilus of fascia dentata. In the dorsal HF labeling was present in the subicular and CA1 field polymorphic layers. The distribution of VTA neurons projecting to the HF was also examined by injecting retrograde fluorescent tracers (Fluoro Gold, Fast Blue, and Nuclear Yellow) in several hippocampal areas. The most abundant VTA-HF projections originate from the upper and lower edges and the lower half of the VTA. These terminal fields in the HF match with the hippocampal areas projecting to the nucleus accumbens. The VTA, via projections to interconnected regions of the HF and nucleus accumbens, may modulate the hypothesized functional link between the limbic system and basal ganglia.

Animals↗

Interaction of cholinergic-dopaminergic systems in the regulation of memory storage in aversively motivated learning tasks.

These experiments examined the interaction between muscarinic cholinergic and dopaminergic systems in the modulation of memory storage. Male CD1 mice (25-30 g) were trained in an inhibitory avoidance (IA) and a Y-maze discrimination (YMD) task. The first experiment examined the dose-response effects, on retention, of agonists and antagonists specific for either D1- or D2-receptors. Immediately posttraining mice were given i.p. injections of saline, the D1-receptor agonists SKF 38393 (3.0, 10.0 or 30.0 mg/kg) or SKF 77434 (3.0, 10.0 or 30.0 mg/kg), the D1-receptor antagonist SCH 23390 (0.03, 0.1, or 1.0 mg/kg), the D2-receptor agonist quinpirole (0.3, 1.0 or 3.0 mg/kg) or the D2-receptor antagonist sulpiride (3.0, 10.0, 30.0 or 100.0 mg/kg). Retention was tested 48 h later. The drugs affecting D1-receptors did not affect retention. In contrast, in both tasks quinpirole enhanced retention and sulpiride impaired retention. In the IA task, quinpirole (3.0 mg/kg) blocked the retention impairing effects of the muscarinic cholinergic antagonist atropine (10.0 mg/kg), and sulpiride (3.0, 10.0, 30.0 or 100.0 mg/kg) significantly attenuated the memory enhancing effects of the muscarinic cholinergic agonist oxotremorine (35.0 or 70.0 micrograms/kg). D1-receptor agents did not modify the effects of either atropine or oxotremorine on retention of the IA response. These findings suggest that the effects of cholinergic muscarinic agents on retention of the IA response are mediated by influences involving D2-dopaminergic mechanisms. In the YMD task, atropine (10.0 mg/kg) blocked the memory-enhancing effects of quinpirole (3.0 mg/kg) and oxotremorine (35.0 or 70.0 micrograms/kg) attenuated the memory impairing effect of sulpiride (3.0, 10.0, 30.0 or 100.0 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Organization of the projections from the ventral tegmental area of Tsai to the hippocampal formation in the rat.

The projection from the ventral tegmental area of Tsai (VTA-A10) to the hippocampal formation (HF) has been investigated in the rat by means of the Fink-Heimer technique, after VTA destruction by electrolytic lesions or local injections of 6-hydroxydopamine (6-OHDA, 1 microgram/0.5 microliters). Degenerated axons prevail in the ventral subiculum and adjacent CA1 field. Some degenerated fibers are also observed in the dorsal subiculum and a few in the stratum oriens of the CA3, in the hilus of fascia dentata and in the fimbria. The distribution of VTA neurons projecting to the HF has also been examined by injecting retrograde fluorescent tracers in different combinations (Fast Blue, 2% and Nuclear Yellow, 1%) in several hippocampal areas. The most abundant VTA-HF projections originate from the lower third, the upper and lower edges and the lower half of the VTA. The major terminal fields of VTA projections in the HF (i.e. the ventral subiculum, the adjacent CA1 field and the dorsal subiculum) match with the HF area projecting to the nucleus accumbens. Thus, the dopaminergic meso-limbic pathway could modulate the HF-striatal projection which provides a link between the limbic and motor systems.

Animals↗