PARP inhibition: A promising therapeutic target in ovarian cancer.

Ovarian cancer is burdened by the highest mortality rate among gynecological cancers. Gold standard is represented by the association of platinum-taxane -based chemotherapy and radical surgery. Despite several adjustments occurred in cytotoxic drug in last decades, most patients continue to relapse, and no significant enhancement has been reached in the overall survival. The development of drug resistance and the recurrence of disease have prompted the investigations of other targets that can be used in the treatment of ovarian cancers. Among such targets, polyadenosine diphosphate-ribose polymerase (PARP) represents a novel way to target specific patways involved in tumor growth. PARP accelerates the reaction of the polyADP-ribosylation of proteins implicated in DNA repair. PARP inhibitors have shown activity in cancers with BRCA mutations, with other deficient DNA repair genes or signaling pathways that modulate DNA repair, or in association with DNA damaging agents not involved in DNA repair dysfunction. A number of inhibitors for PARP has been developed, and such drugs are under investigation in clinical trials to identify their impact in the treatment of ovarian cancers. This review aims to summarize the recent researches and clinical progress on PARP inhibitors as novel target agents in ovarian cancer.

Postsynaptic alteration of NR2A subunit and defective autophosphorylation of alphaCaMKII at threonine-286 contribute to abnormal plasticity and morphology of upper motor neurons in presymptomatic SOD1G93A mice, a murine model for amyotrophic lateral sclerosis.

Although amyotrophic lateral sclerosis (ALS) has long been considered as a lower motor neuron (MN) disease, degeneration of upper MNs arising from a combination of mechanisms including insufficient growth factor signaling and enhanced extracellular glutamate levels is now well documented. The observation that these mechanisms are altered in presymptomatic superoxide dismutase (SOD1) mice, an ALS mouse model, suggests that defective primary motor cortex (M1) synaptic activity might precede the onset of motor disturbances. To examine this point, we assessed the composition of AMPAR and NMDAR subunits and of the alphaCa²(+)/calmodulin-dependent kinase autophosphorylation at threonine-286 in the triton insoluble fraction from the M1 in postnatal P80-P85 SOD1(G93A) and wild-type mice. We show that presymptomatic SOD1(G93A) exhibit a selective decrease of NR2A subunit expression and of the alphaCa²(+)/calmodulin-dependent kinase autophosphorylation at threonine-286 in the triton insoluble fraction of upper MNs synapses. These molecular alterations are associated with synaptic plasticity defects, and a reduction in upper MN dendritic outgrowth revealing that abnormal neuronal connectivity in the M1 region precedes the onset of motor symptoms. We suggest that the progressive disruption of M1 corticocortical connections resulting from the SOD1(G93A) mutation might extend to adjacent regions and promote development of cognitive/dementia alterations frequently associated with ALS.

Insulin-like growth factor-I (IGF-1), IGF-binding protein-3 (IGFBP-3) and mammographic features.

INTRODUCTION: The IGF system has recently been shown to play an important role in the regulation of breast tumor cell proliferation. However, also breast density is currently considered as the strongest breast cancer risk factor. It is not yet clear whether these factors are interrelated and if and how they are influenced by menopausal status. The purpose of this study was to examine the possible effects of IGF-1 and IGFBP-3 and IGF-1/IGFBP-3 molar ratio on mammographic density stratified by menopausal status. PATIENTS AND METHODS: A group of 341 Italian women were interviewed to collect the following data: family history of breast cancer, reproductive and menstrual factors, breast biopsies, previous administration of hormonal contraceptive therapy, hormone replacement therapy (HRT) in menopause and lifestyle information. A blood sample was drawn for determination of IGF-1, IGFBP-3 levels. IGF-1/ IGFBP-3 molar ratio was then calculated. On the basis of recent mammograms the women were divided into two groups: dense breast (DB) and non-dense breast (NDB). Student's t-test was employed to assess the association between breast density and plasma level of IGF-1, IGFBP-3 and molar ratio. To assess if this relationship was similar in subgroups of pre- and postmenopausal women, the study population was stratified by menopausal status and Student's t-test was performed. Finally, multivariate analysis was employed to evaluate if there were confounding factors that might influence the relationship between growth factors and breast density. RESULTS: The analysis of the relationship between mammographic density and plasma level of IGF-1, IGFBP-3 and IGF-1/ IGFBP-3 molar ratio showed that IGF-1 levels and molar ratio varied in the two groups resulting in higher mean values in the DB group (IGF-1: 109.6 versus 96.6 ng/ml; p= 0.001 and molar ratio 29.4 versus 25.5 ng/ml; p= 0.001) whereas IGFBP-3 showed similar values in both groups (DB and NDB). Analysis of plasma level of IGF-1, IGFBP-3 and IGF-1/IGFBP-3 molar ratio compared to breast density after stratification of the study population by menopausal status (premenopausal and postmenopausal) showed that there was no association between the plasma of growth factors and breast density, neither in premenopausal nor in postmenopausal patients. Multivariate analysis showed that only nulliparity, premenopausal status and body mass index (BMI) are determinants of breast density. CONCLUSIONS: Our study provides a strong evidence of a crude association between breast density and plasma levels of IGF-1 and molar ratio. On the basis of our results, it is reasonable to assume that the role of IGF-1 and molar ratio in the pathogenesis of breast cancer might be mediated through mammographic density. IGF-1 and molar ratio might thus increase the risk of cancer by increasing mammographic density.

Efficacy and safety of robotic-assisted surgery in challenging hysterectomies - a single institutional experience.

OBJECTIVE: An increasing number of robotic hysterectomies are being performed and the most common indication is fibroids. Fibroid uterus is common indication for hysterectomy for enlarged uteri. The role of robotic approach for complex pathologies as enlarged uterus is still debatable. The study aimed to analyze the feasibility of robotic hysterectomy in patients with enlarged uteri and the impact of uterine weight on surgical outcomes and on operative time length. PATIENTS AND METHODS: One hundred and thirty-eight patients who underwent robotic hysterectomy for benign indications at the 2nd Division of Obstetrics and Gynecology, Azienda Ospedaliero-Universitaria Pisana, University of Pisa were consecutively enrolled. RESULTS: Data of patients undergoing robotic surgery for benign indications were collected. Patients were stratified in two groups based on their uterine weight, to analyze the effective impact of uterine weight and dimension on surgical performance, operative time and postoperative outcomes. Conversion rate was 0%. Median uterine weight was 615 g (range 400-1900 g). Median total operating time was 131 minutes (range 70-255 minutes). Increase in uterine weight significantly increased operative times (p=0.003) and morcellation time (p=0.001). On the other hand, operative time was just partially influenced by route for removal of the uterus (p=0.085) but significantly affected by uterine weight (p=0.008), previous surgeries (p=0.003) and BMI of the patient (p=0.005). CONCLUSIONS: Robotic hysterectomy is feasible and safe for challenging cases as large uteri. This technique could enable patients with outsized uteri, not suitable for vaginal hysterectomy, to undergo minimally invasive surgery with excellent results. Larger studies to investigate and compare robotic with other surgical approaches for difficult hysterectomies are needed to confirm these data.

Effective combined treatment in ectopic cervical pregnancy preserving fertility: a case report and literature review.

OBJECTIVE: Cervical ectopic pregnancy (CEP) is a rare obstetric complication but carries the risk of life-threatening maternal hemorrhage. CASE PRESENTATION: A 43-year-old nulliparous woman, presented to the Emergency Room with vaginal bleeding. Initial quantitative serum ß-hCG value was 85,220 mIU/mL. Obstetrical ultrasound demonstrated a single, live pregnancy of approximately 9 weeks' gestation located within the endocervix. After discussing different management options, intramuscular methotrexate injection in association with intra-amniotic chloride potassium installation was decided in order to preserve patient's desire for childbearing. Three months later, the patient was readmitted due to a massive vaginal bleeding. Angiographic uterine artery embolization (UAE) with an absorbable gelatin sponge was performed. After the procedure and two days of hospitalization, no significative bleeding was observed. The clinical course was uneventful, and serum human chorionic gonadotropin decreased immediately. The cervical mass gradually shrank and disappeared a month after UAE. CONCLUSIONS: To preserve fertility in the management of CEP, clinicians could consider a combination of strategies, including UAE. A review of the current literature and possible treatment options for conservative CEP management are analyzed and discussed.

Blocking the NGF-TrkA interaction rescues the developmental loss of LTP in the rat visual cortex: role of the cholinergic system.

Although nerve growth factor (NGF) is a crucial factor in the activity-dependent development and plasticity of visual cortex, its role in synaptic efficacy changes is largely undefined. We demonstrate that the maintenance phase of long-term potentiation (LTP) is blocked by local application of exogenous NGF in rat visual cortex at an early stage of postnatal development. Long-term depression (LTD) and bidirectional plasticity are unaffected. At later postnatal ages, blockade of either endogenous NGF by immunoadhesin (TrkA-IgG) or TrkA receptors by monoclonal antibody rescues LTP. Muscarinic receptor activation/inhibition suggests that LTP dependence on NGF is mediated by the cholinergic system. These results indicate that NGF regulates synaptic strength in well-characterized cortical circuitries.

Safety and efficacy of tigecycline in complicated and uncomplicated pelvic inflammatory disease.

OBJECTIVE: Tigecycline is a glycylcycline antimicrobial structurally related to minocycline, with a wide spectrum of activity that includes anaerobes and typical and atypical microorganisms causing pelvic inflammatory disease (PID). This study aimed to evaluate efficacy and safety of tigecycline in complicated PID and un-complicated PID after the failure of first-line antibiotic therapy. PATIENTS AND METHODS: Between May 2014 and April 2016 at the 2nd Unit of Obstetrics and Gynecology, Santa Chiara Hospital of Pisa a pilot study on 20 women with mild/moderate PID after the failure of first-line antibiotic therapy and on 8 women with complicated PID was conducted. The treatment protocol was 10-day course of tigecycline, with a loading dose of 100 mg intravenously (i.v.) at day one and then 50 mg IV twice daily. The primary endpoint was to evaluate tigecycline's efficacy in terms of clinical response to test-of-cure (TOC) at the end of therapy and 30 days after the last dose. Clinical response during therapy and safety were analyzed as well. RESULTS: A total of 28 women were enrolled, and 25 patients completed the study protocol, because 3 patients reported adverse drug effects resulting in treatment interruption. PID was mainly caused by Chlamydia, Gardnerella, Mycoplasma/Ureaplasma. Tigecycline showed a 100% remission of signs and symptoms in patients resistant to first-line antibiotic regimen and in patients with complicated PID. Moreover, tigecycline showed good tolerability and compliance. CONCLUSIONS: Despite the limited sample size, tigecycline seemed an effective and safe treatment for women with complicated/resistant PID. Nevertheless, further clinical trials are needed to confirm these results.

Clinical outcomes after resectoscopic treatment of cesarean-induced isthmocele: a prospective case-control study.

OBJECTIVE: Isthmocele represents a reservoir on the anterior wall of the uterine isthmus or of the cervical canal at the site of a previous cesarean delivery scar. Recently, it has been clarified that it might be the cause of several gynecologic symptoms, as most common abnormal uterine bleeding. Hysteroscopy and trans-vaginal ultrasound are considered the gold standard for the diagnosis of this defect. Resectoscopic treatment can be considered effective in small size defects, but no randomized clinical trials are available. This is a prospective controlled study to assess feasibility and efficacy of surgical hysteroscopic treatment of cesarean-induced isthmocele on symptom relief. PATIENTS AND METHODS: Diagnostic hysteroscopy was performed as an office procedure in all 47 patients included in the study to confirm and identify the size of the defect. Surgical hysteroscopic treatment was performed in a selected group of patients (n = 23) having no more desire to conceive. Outcomes were measured three months later and compared in the operative hysteroscopy versus diagnostic hysteroscopy group. RESULTS: The duration of periods shortened significantly (p = 0.0003) compared with the duration of menses before operative hysteroscopy in the treated group. Moreover, symptom relief was significantly better in treated patients compared with controls (p < 0.0001). CONCLUSIONS: Resectoscopic treatment of isthmocele offers the possibility of an effective, safe and well-tolerated resolution of associated bleeding symptoms, having an excellent impact on the length of menses. To our knowledge, this is the first prospective controlled trial demonstrating better outcomes of resectoscopic treatment of isthmocele in solving symptoms compared with expectant management.

D-mannose: a promising support for acute urinary tract infections in women. A pilot study.

OBJECTIVE: Urinary tract infections still represent a significant bother for women and result in high costs to the health system. D-mannose is a simple sugar; it seems able to hinder bacteria adhesion to the urothelium. The present study aimed to determine whether D-mannose alone is effective in treating acute urinary tract infections in women and its possible utility in the management of recurrences. PATIENTS AND METHODS: This is a pilot study, performed between April 2014 and July 2015 at Department of Gynaecological Obstetrics and Urologic Sciences of "Sapienza" University of Rome. A D-mannose compound was administered twice daily for 3 days and then once a day for 10 days. Changes in patients' symptoms, the therapeutic effects and changes in quality of life (QoL) were evaluated clinically and using a specifically validated questionnaire (UTISA). After described treatment, patients were randomized in receiving or not prophylaxis in the next 6 months. RESULTS: Mean UTISA scores recorded after completing the treatment, compared with baseline scores, showed a significant improvement of the majority of symptoms (p < 0.05). D-mannose seemed to have had a significant positive effect on UTIs' resolution and QoL improvement (p = 0.0001). As prophylactic agent administered for 6 months, it showed promising results (4.5% vs. 33.3% recurrences in treated and untreated patients respectively). CONCLUSIONS: The results of this study suggest that D-mannose can be an effective aid in acute cystitis management and also a successful prophylactic agent in a selected population; however, more studies will certainly be needed to confirm the results of our pilot study.

Impaired synaptic plasticity in the visual cortex of mice lacking α7-nicotinic receptor subunit.

The primary visual cortex (V1) is the first step in visual information processing and its function may be modulated by acetylcholine through nicotinic receptors (nAChRs). Since our previous work demonstrated that visual acuity and cortical spatial resolution limit were significantly reduced in α7 knock-out (KO) mice in the absence of retinal alterations, we decided to characterize the contribution of homomeric α7 nicotinic receptors (α7nAChRs) to visual information processing at the cortical level. We evaluated long-term forms of synaptic plasticity in occipital slices containing V1 from α7 KO mice and in wild-type (WT) slices perfused with nAChRs selective blocking agents. In α7 KO mice slices, electrophysiological recordings demonstrated the absence of long-term potentiation (LTP) and long-term depression (LTD) in layer II/III after the stimulation of different intracortical pathways (layer IV or II/III). Furthermore, the acute and selective blockade of α7nAChRs in slices from WT mice with either α-bungarotoxin or methyllycaconitine did not alter the expression of LTP and LTD. Conversely, the perfusion with the unspecific nAChRs antagonist mecamylamine impaired LTP and LTD. Our results suggest the presence of impaired synaptic plasticity in the V1 of α7 KO mice and indicate a different contribution of nAChRs to visual cortex function.

Exogenous supply of nerve growth factor prevents the effects of strabismus in the rat.

It has recently been reported that exogenous supply of nerve growth factor prevents the effects of monocular deprivation both in rats and in cats. Here we have extended these experiments to the case of strabismus. Repeated intraventricular injections of nerve growth factor were performed in rats made surgically strabismic early in the critical period. At the end of the critical period the ocular dominance distribution of visual cortical neurons was assessed in strabismic untreated, strabismic nerve growth factor-treated and strabismic Cytochrome C-treated (control) rats by means of extracellular recordings. We found that in rats surgical strabismus causes a consistent loss of binocular neurons. By contrast the treatment with nerve growth factor maintains the normal ocular dominance distribution of neurons in the primary visual cortex. We conclude that nerve growth factor exogenously supplied prevents the effects induced by surgical strabismus in rats and suggest that nerve growth factor has a role in visual cortical plasticity.

Co-expression of TrkB and the N-methyl-D-aspartate receptor subunits NR1-C1, NR2A and NR2B in the rat visual cortex.

In the visual cortex, brain-derived neurotrophic factor expression is modulated through glutamate receptors, including the N-methyl-D-aspartate glutamate receptor. It has been proposed that the N-methyl-D-aspartate glutamate receptor subunit composition itself might be regulated by brain-derived neurotrophic factor. Here, we investigated the co-expression of the neurotrophin-4/brain-derived neurotrophic factor receptor TrkB with the N-methyl-D-aspartate glutamate receptor subunits NR1-C1, NR2A and NR2B, on postnatal days 10 and 22 and in the adult rat primary visual cortex. At both postnatal days 10 and 22, TrkB is co-expressed in all cortical layers with the studied N-methyl-D-aspartate glutamate receptor subunits. In the adult, in layers IV-V, co-expression is restricted to a subpopulation of neurons, while in layers II-III, VI nearly all neurons co-express TrkB with NR1-C1, NR2A and NR2B. We conclude that in layers IV-V, the co-expression of TrkB with subunits NR2B and NR2A is developmentally regulated.

A new form of synaptic plasticity is transiently expressed in the developing rat visual cortex: a modulatory role for visual experience and brain-derived neurotrophic factor.

Synaptic plasticity has been implicated in the mechanisms contributing to the shaping of the cortical circuits responsible for the transmission of the visual input in the rat primary visual cortex. However, the degree of plasticity of the thalamocortical synapse may change during development, perhaps reflecting the degree of stabilization of the circuitry subserving it. We have chosen the ability of this synapse to be first depressed and then potentiated as a specific indicator of its plasticity. In this study we have investigated how this parameter changes during development and the factors controlling it. Extracellular field potentials in cortical layers 2/3 were evoked by stimulation of the white matter in rat primary visual cortex slices prepared at different postnatal ages. Low-frequency stimulation (900 pulses at 1 Hz) of the white matter was used to induce long-term depression of field potential amplitude, whereas long-term potentiation was evoked by high-frequency stimulation consisting of three trains at 100 Hz. We provide evidence that while it is possible to potentiate previously depressed synapses soon after eye opening (postnatal day 17) this synaptic characteristic decreases rapidly thereafter. The decrease in this form of cortical synaptic plasticity closely matches the stabilization of the cortical circuitry towards an adult pattern of connectivity and function. Depressed cortical synapses cannot be potentiated in normal rats at postnatal 23, but they can be potentiated in rats reared in the dark from postnatal days 17 to 29. Moreover, application of brain-derived neurotrophic factor, known to be expressed in an activity-dependent manner, was able to restore the ability of synapses to be potentiated after long-term depression, thus indicating its important modulatory role in brain development.

Parvalbumin immunoreactivity: a reliable marker for the effects of monocular deprivation in the rat visual cortex.

In mammals, monocular deprivation performed during the early stages of postnatal development (critical period) dramatically affects the functional organization of the visual cortex. Since the early work of Hubel and Wiesel, the effects of monocular deprivation are accounted for by the fibers driven by the two eyes competing for the control of cortical territories. In cat and monkey striking structural changes accompany the functional effects of monocular deprivation. Also, in the rat, monocular deprivation causes functional alteration at the level of visual cortex; no structural correlates of these effects, however, have so far been described. Parvalbumin is a calcium binding protein that in the neocortex colocalizes with a subpopulation of GABAergic neurons. Here we report that in the rat monocular deprivation results in a dramatic reduction of parvalbumin-like immunoreactivity in the visual cortex contralateral to the deprived eye. This effect is due to competitive phenomena and not to visual deprivation itself, it is restricted to the binocular portion of the visual cortex and neither binocular deprivation, nor dark rearing can induce it. We conclude that parvalbumin-like immunoreactivity is a useful immunohistochemical marker for the effects of monocular deprivation in the rat visual cortex.

Dark rearing blocks the developmental down-regulation of brain-derived neurotrophic factor messenger RNA expression in layers IV and V of the rat visual cortex.

In this study, we describe the distribution of brain-derived neurotrophic factor messenger RNA in the binocular primary visual cortex of the rat during postnatal development, starting at postnatal day (P) 13. High-resolution non-isotopic in situ hybridization combined with Nissl staining were used to quantify the number of cells expressing brain-derived neurotrophic factor messenger RNA. At P13, most of the cells express brain-derived neurotrophic factor messenger RNA. After eye opening (P14-P15), the relative number of brain-derived neurotrophic factor messenger RNA-positive cells decreases by a factor of two in layer IV, i.e. that receiving the visual input, and in layer V. To verify the hypothesis that light could trigger this decrease, pups were kept in complete darkness from birth. At P22, pups reared in the dark were killed and the visual cortex processed for in situ hybridization and northern blotting. The results obtained in dark-reared animals prove that light deprivation can: (i) decrease the general levels of brain-derived neurotrophic factor messenger RNA, and (ii) increase the relative number of brain-derived neurotrophic factor messenger RNA-positive cells in layers IV and V with respect to control rats. Exposure to light for five days after the period of darkness restored the number of brain-derived neurotrophic factor messenger RNA-positive cells. We conclude that the expression of brain-derived neurotrophic factor messenger RNA in the rat primary visual cortex is regulated during development and that this process is under the control of visual input.

Differential regulation of brain-derived neurotrophic factor messenger RNA cellular expression in the adult rat visual cortex.

In this study, we report a comparative analysis of the distribution of brain-derived neurotrophic factor messenger RNA in the binocular primary visual cortex of rats analysed at the end of the critical period for monocular deprivation (postnatal day 35) and during adulthood (postnatal day 90). High-resolution non-isotopic in situ hybridization coupled with Nissl staining allowed to determine the relative number of neurons expressing brain-derived neurotrophic factor messenger RNA. In postnatal day 90 rats, the relative number of neurons positive for brain-derived neurotrophic factor messenger RNA significantly decreases in layer II/III with respect to postnatal day 35 animals, being constant in all the other cortical layers. Moreover, we demonstrate that dark rearing for 22 days, starting from postnatal day 90, determines: (i) a decrease of the overall level of brain-derived neurotrophic factor messenger RNA with a consequent reduction of labelling intensity in all cells throughout cortical layers II-VI; (ii) an increase of cell numbers expressing brain-derived neurotrophic factor messenger RNA in layers IV and V; and (iii) a decreased intensity of staining for brain-derived neurotrophic factor messenger RNA in dendrites after dark rearing. A re-exposure to light for 2 h after the period of darkness almost restores the number of brain-derived neurotrophic factor RNA-positive neurons. We conclude that the maturation of brain-derived neurotrophic factor messenger RNA in neurons of layer II/III goes beyond postnatal days 35-40, which can be considered the end of the critical period [Fagiolini M. et al. (1994) Vis. Res., 34, 709-720]. Moreover, we show that the cellular expression of brain-derived neurotrophic factor messenger RNA is regulated by light in adult rats as well as during development.

Dark-rearing decreases NR2A N-methyl-D-aspartate receptor subunit in all visual cortical layers.

Maturation of the visual cortex is a visual experience-dependent process. It has been shown that visual input triggers changes in N-methyl-D-aspartate receptor (NMDAR) subunit expression in the visual cortex. However, no data are available on the layer distribution of these molecular changes. Here we describe the laminar distribution of the cells expressing the NMDAR subunits NR2A and NR2B in the rat primary visual cortex at postnatal day (P) 21 and 37 using anti-NR2A and anti-NR2B antibodies and a stereological method to count labelled neurons. The percentage of neurons expressing the NR2A subunit in the layers II-VI remained unchanged between P21 and P37 with a slight decrease in layer V. Dark-rearing from P21 to P37 induced a pronounced decrease of the staining intensity and a significant decrease in the percentage of NR2A-expressing neurons. The changes in NR2A expression caused by dark rearing occur at similar levels in layers II-VI. The percentage of NR2B-positive cells in the different cortical layers remains unchanged from P21 to P37. The NR2B pattern was not significantly affected by dark-rearing. Thusly, the expression of NR2A depends upon visual experience after P21.

Distribution of GABA-like immunoreactivity in the pigeon brain.

The distribution of GABA-like immunoreactivity in glutaraldehyde-fixed pigeon brains was studied by means of a monoclonal antibody. GABA-like immunoreactivity was observed in neuronal perikarya of different sizes as well as in neuropil and in certain fiber tracts. Certain staining patterns indicated the existence of several GABAergic projection systems in the pigeon brain. Indeed, a high density of immunostained perikarya and a low density of labeled terminal-like elements was the prominent pattern in the nuclei subpretectalis and posteroventralis, while an absence of perikaryal GABA-like immunoreactivity and accumulations of immunoreactive dots were observed in the isthmo-optic nucleus, amongst others. In the optic tectum, stained cell bodies with radially oriented processes in layer IIi (10) and with horizontally oriented processes in layer IId (5) were seen and were reminiscent of autoradiographic labeling patterns obtained previously following tectal injection of tritiated GABA. In the cerebellum, GABA-like immunoreactivity involved all types of neurons with the exception of granule cells. Purkinje cells showed regionally different intensities of immunostaining. In addition, in folium X no stained basket-like elements were observed. Although there is no evidence as yet about the function of GABA in most of the structures, the present results indicate an important role for this neurotransmitter in the pigeon brain.