Living with young-onset dementia in the family - a mixed method study.

Background: Studies on disease-related obstructions experienced in everyday life of younger people with dementia (YOD ≤ 65 years) and their families are encouraged.Aim: To explore how the family carers experience six predefined topics that influence the everyday life and needs of persons with YOD.Method: A quantitative and a qualitative study including family carers of persons with young-onset Alzheimer's dementia (AD) and frontotemporal dementia (FTD). Seventy-four informants responded to the Camberwell Assessment of Needs in the Elderly (CANE) and individual interviews were conducted with 13 informants.Results: Family carers of persons with YOD reported few unmet needs in the CANE assessment. Needs related to behavior and close relationships were reported significantly more frequent (p < 0.1) in persons with FTD than in persons with AD. From the qualitative data, six main themes were emphasized: daily activities turned upside down, involuntary loss of previous social network, losing close relationship, but maintaining a friendship with the spouse, unpredictable behavior adds burdens to a changing life, health and life risks, and economic insecurity for future life and caring costs.Conclusion: Whilst family carers quantitatively reported unmet needs, the individual interviews reported several major difficulties in everyday life.

Blockade of dopamine D2 receptors disrupts intrahippocampal connectivity and enhances pain-related working memory deficits in neuropathic pain rats.

BACKGROUND: Dopamine (DA) is thought to be important to local hippocampal networks integrity during spatial working memory (sWM) processing. Chronic pain may contribute to deficient dopaminergic signalling, which may in turn affect cognition. However, the neural mechanisms that determine this impairment are poorly understood. Here, we evaluated whether the sWM impairment characteristic of animal models of chronic pain is dependent on DA D2 receptor (D2r) activity. METHODS: To address this issue, we implanted multichannel arrays of electrodes in the dorsal and ventral hippocampal CA1 field (dvCA1) of rats and recorded the neuronal activity during a classical delayed food-reinforced T-maze sWM task. Within-subject behavioural performance and patterns of dorsoventral neural activity were assessed before and after the onset of persistent neuropathic pain using the spared nerve injury (SNI) model. RESULTS: Our results show that the peripheral nerve lesion caused a disruption in sWM and hippocampus spike activity and that disruption was maximized by the systemic administration of the D2r antagonist raclopride. These deficits are strictly correlated with a selective disruption of hippocampal theta-oscillations. Particularly, we found a significant decrease in intrahippocampal CA1 field connectivity level. CONCLUSIONS: Together, these results suggest that disruption of the dopaminergic balance in the intrahippocampal networks may be important for the development of cognitive deficits experienced during painful conditions. SIGNIFICANCE: This study provides new insights into the role of D2r in the manifestation of pain-related sWM deficits. Our findings support that selective blockade of D2r produces a significant decrease in intrahippocampal connectivity mediated by theta-oscillations, and amplifies pain-related sWM deficits. These results suggest that further characterization of intrahippocampal dopaminergic modulation may be clinically relevant for the understanding of cognitive impairments that accompanies nociceptive stressful conditions.

Young-onset Alzheimer dementia: a comparison of Brazilian and Norwegian carers' experiences and needs for assistance.

OBJECTIVES: Although dementia typically occurs in older people, it can also emerge in people aged younger than 65 years in the form of young-onset dementia, the most common type of which is Alzheimer's disease (AD). However, few studies have examined the needs of persons with young-onset AD (YO-AD) and their families, and cross-cultural research on the topic is even scarcer. In response, we investigated the situations, experiences and needs for assistance of carers of persons with YO-AD in Brazil and Norway. METHODS: As part of our qualitative study, we formed a convenience sample of Brazilian (n = 9; 7 women) and Norwegian carers (n = 11; 6 women) in 2014 and 2015, respectively, and analysed data in light of a modified version of grounded theory. RESULTS: Carers' narratives from both countries revealed five common themes in terms of how YO-AD affected carers' psychological and emotional well-being, physical well-being, professional and financial well-being, social lives and need for support services. CONCLUSIONS: The infrequent differences between carers of persons with YO-AD in Brazil and Norway indicate that carers' problems are highly similar regardless of cultural differences and public services provided. Copyright © 2017 John Wiley & Sons, Ltd.

Extracellular vesicles from oral squamous carcinoma cells display pro- and anti-angiogenic properties.

BACKGROUND: A new intercellular communication mode established by neoplastic cells and tumor microenvironment components is based on extracellular vesicles (EVs). However, the biological effects of the EVs released by tumor cells on angiogenesis are not completely understood. Here, we aimed to understand the biological effects of EVs isolated from two cell lines of oral squamous cell carcinoma (OSCC) (SCC15 and HSC3) on endothelial cell tubulogenesis. METHODS: OSCC-derived EVs were isolated with a polymer-based precipitation method, quantified using nanoparticle tracking analysis and verified for EV markers by dot blot. Functional assays were performed to assess the angiogenic potential of the OSCC-derived EVs. RESULTS: The results showed that EVs derived from both cell lines displayed typical spherical-shaped morphology and expressed the EV markers CD63 and Annexin II. Although the average particle concentration and size were quite similar, SCC15-derived EVs promoted a pronounced tubular formation associated with significant migration and apoptosis rates of the endothelial cells, whereas EVs derived from HSC3 cells inhibited significantly endothelial cell tubulogenesis and proliferation. CONCLUSION: The findings of this study reveal that EVs derived from different OSCC cell lines by a polymer-based precipitation method promote pro- or anti-angiogenic effects.

Head and neck cancer among marijuana users: a meta-analysis of matched case-control studies.

OBJECTIVES: The scientific literature presents conflicting data on a possible causal relationship between marijuana users and the development of head and neck cancer. DESIGN: This study performed a systematic review with meta-analysis. Articles were selected from various electronic databases using keywords obtained from the Medical Subject Headings (MeSH). After reading by three reviewers and scoring of methodological quality, six articles (totaling nine case-control studies) were assessed with Comprehensive Meta-Analysis(®) software. The value of effect (odds ratio) was calculated, which represented the chance of developing head and neck cancer between individuals who had smoked marijuana in their lifetime in models controlled for age, gender, race, and tobacco consumption. RESULTS: Approximately 12.6% of cases and 14.3% of controls were marijuana users. The meta-analysis found no association between exposure and disease (OR=1.021; IC 95%=0.912-1.14; p=0.718). CONCLUSION: No association between lifetime marijuana use and the development of head and neck cancer was found. The different methods of collection/presentation of results in the selected articles prevented other analyzes from being conducted. Additional studies are needed to assess for long-term effects.

Antioxidant enzymes activities of Burkholderia spp. strains-oxidative responses to Ni toxicity.

Increased agriculture production associated with intense application of herbicides, pesticides, and fungicides leads to soil contamination worldwide. Nickel (Ni), due to its high mobility in soils and groundwater, constitutes one of the greatest problems in terms of environmental pollution. Metals, including Ni, in high concentrations are toxic to cells by imposing a condition of oxidative stress due to the induction of reactive oxygen species (ROS), which damage lipids, proteins, and DNA. This study aimed to characterize the Ni antioxidant response of two tolerant Burkholderia strains (one isolated from noncontaminated soil, SNMS32, and the other from contaminated soil, SCMS54), by measuring superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione S-transferase (GST) activities. Ni accumulation and bacterial growth in the presence of the metal were also analyzed. The results showed that both strains exhibited different trends of Ni accumulation and distinct antioxidant enzymes responses. The strain from contaminated soil (SCMS54) exhibited a higher Ni biosorption and exhibited an increase in SOD and GST activities after 5 and 12 h of Ni exposure. The analysis of SOD, CAT, and GR by nondenaturing PAGE revealed the appearance of an extra isoenzyme in strain SCMS54 for each enzyme. The results suggest that the strain SCMS54 isolated from contaminated soil present more plasticity with potential to be used in soil and water bioremediation.

Association between executive/attentional functions and caries in children with cerebral palsy.

The aim of the present study was to evaluate the existence of an association between attention/executive functions and the development of dental caries in individuals with cerebral palsy (CP). Seventy-six children with CP were selected from a physical rehabilitation center and a school serving children with disabilities. The control group was made up of 89 children without neurological impairment. Socioeconomic status, presence of teeth with cavities due to caries, degree of motor impairment and intellectual, executive and attentional functions were assessed. Mean age of participants was 8.9 years (SD=3.56). The CP group had a significantly lower performance (p<0.05, Mann-Whitney test) on the intelligence, attentional function and executive function tests in comparison to the control group. Controlling for the clinical diagnosis (CP or control group), motor impairment and intellectual function, the significant explanatory variables for the presence of teeth with cavities were performance on the Complex Rey figure test (OR=0.941) and the Digit Span subtest of the Wechsler Intelligence Scale for Children in backward order (OR=0.581). After controlling for intellectual function, clinical diagnosis and motor impairment, deficits in executive and attentional functions increased the odds of developing dental caries in children with cerebral palsy.

Apoptosis deregulation influences chemoresistance to azaguanine in human leukemic cell lines.

The involvement of apoptosis in the cytotoxicity mediated by nucleoside analogues, namely azaguanine, and its implication in resistance are not well understood. Using human T-cell acute lymphoblastic leukemia cell lines, sensitive (CEM cells) and resistant to azaguanine (CM3 cells), we observe a decrease in the expression of proapoptotic proteins in CM3 cells, which may be related to the resistance to cell death induced by azaguanine. On the other hand, CM3 cells lack cross resistance with other anticarcinogenic drugs, suggesting that azaguanine may be used alternatively in the presence of chemoresistance. A better knowledge of the apoptotic pathways involved in leukemic cell death resistance may contribute to the development of therapeutic strategies, aimed to prevent chemotherapy resistance.

Clinical characteristics of Guillain-Barré syndrome in a tropical country: a Brazilian experience.

OBJECTIVE: To analyze the clinical variants, outcomes, and prognosis of Guillain-Barré syndrome (GBS) in a Brazilian population. MATERIALS AND METHODS: Clinical and laboratory data of 149 cases of GBS diagnosed from 1994 to 2007 were analyzed. RESULTS: Acute inflammatory demyelinating polyneuropathy (AIDP) was the most frequent variant (81.8%) of GBS, followed by acute motor axonal neuropathy (AMAN) (14.7%) and acute motor and sensory axonal neuropathy (AMSAN) (3.3%). The incidence of GBS was 0.3/100,000 for the state of Rio Grande do Norte and cases occurred at a younger age. GBS was preceded by infections, with the axonal variant associated with episodes of diarrheas (P = 0.025). Proximal weakness was more frequent in AIDP, and distal weakness predominant in the axonal variant. Compared to 42.4% of cases with AIDP (P < 0.0001), 84.6% of cases with the axonal variant had nadir in <10 days. Individuals with the axonal variant took longer to recover deambulation (P < 0.0001). The mortality of GBS was 5.3%. CONCLUSION: A predominance of the AIDP variant was seen, and the incidence of the disease decreased with age. As expected, the distribution of weakness correlated with the clinical variants, and individuals with the axonal variant had a poorer prognosis.

Are adverse effects of antiepileptic drugs different in symptomatic partial and idiopathic generalized epilepsies? The Portuguese-Brazilian validation of the Liverpool Adverse Events Profile.

We report the results of administration of the Portuguese-Brazilian translation of the Liverpool Adverse Events Profile (LAEP) to 100 patients (mean age=34.5, SD=12.12; 56 females), 61 with symptomatic partial epilepsy (SPE) and 39 with idiopathic generalized epilepsy (IGE) (ILAE, 1989) who were on a stable antiepileptic drug (AED) regimen and being treated in a Brazilian tertiary epilepsy center. Carbamazepine was the most commonly used AED (43.0%), followed by valproic acid (32.0%). Two or more AEDs were used by 69.0% of patients. The mean LAEP score (19 questions) was 37.6 (SD=13.35). The most common adverse effects were sleepiness (35.0%), memory problems (35.0%), and difficulty in concentrating (25.0%). Higher LAEP scores were associated with polytherapy with three or more AEDs (P=0.005), female gender (P<0.001), older age (P<0.001), and uncontrolled seizures (P=0.045). The intraclass coefficient (test-retest reliability) for LAEP overall score was 0.848 (95% CI=0.782-0.895), with a range from 0.370 (unsteadiness) to 0.750 (memory problems). Cronbach's α coefficient (internal consistency) was 0.903. The LAEP was highly correlated with Quality of Life in Epilepsy-31 inventory (r=-0.804, P>0.001) and Hospital Anxiety and Depression Scale (Depression: r=0.637, P<0.001; Anxiety: r=0.621, P<0.001) dimensions. LAEP overall scores were similar in people with SPE and IGE and were not helpful in differentiating adverse effects in these two groups. Clinical variables that influenced global LAEP were seizure frequency (P=0.050) and generalized tonic-clonic seizures in the last month (P=0.031) in the IGE group, and polytherapy with three or more AEDs (P=0.003 and P=0.003) in both IGE and SPE groups.

Respiratory muscle strength and quality of life in myotonic dystrophy patients.

INTRODUCTION: Studies on quality of life in myotonic dystrophy (MD) are scarce and the relationship between respiratory muscle strength and health-related quality of life (HRQoL) has yet to be determined. The present study aims to investigate respiratory muscle strength and HRQoL and their relationship in MD patients. METHODS: Twenty-three patients (13 men, aged 40 ± 16 years) with MD were evaluated for pulmonary function, maximal inspiratory and expiratory pressure (MIP and MEP, respectively), sniff nasal inspiratory pressure (SNIP) and HRQoL using the Short Form (SF-36) quality of life questionnaire. RESULTS: Respiratory muscle strength values were 71 ± 20 cmH2O (64 % predicted), 76 ± 32 cmH2O (70 % predicted), and 79 ± 28 cmH2O (80 % predicted) for MEP, MIP, and SNIP respectively. Significant differences were found in the SF-36 domains of physical functioning 58.7 ± 31.4 vs. 84.5 ± 23 (p < 0.01, 95 % CI = 1.6-39.9) and physical problems 43.4 ± 35.2 vs. 81.2 ± 34 (p < 0.001, 95 % CI = 19.4-6.1) when compared with the reference values. According to single linear regression analysis, MIP explains 29 % of the variance in physical functioning, 18 % of physical problems and 20 % of vitality. CONCLUSIONS: Individuals with MD have reduced expiratory muscle strength. HRQoL may be more impaired in some physical domains, which might be influenced by variations in inspiratory muscle strength.

A doença de Alzheimer e o impacto nos cuidadores / Alzheimer's diseases and the impact on the caregivers

A doença de Alzheimer (DA) caracteriza-se por um declínio progressivo e inexorável cognitivo, funcional e comportamental dos pacientes atingidos. À medida que o comprometimento ocorre surge a demanda de ajuda, que aumenta com a progressão da doença. Os cuidadores (parentes ou profissionais) vêm para prover os cuidados necessários. Estes desempenham um papel essencial no manejo da vida diária de pacientes com DA, envolvendo-se em praticamente todos os aspectos que dizem respeito aos cuidados da demência. O declínio dos pacientes (cognitivo, dependência nas atividades de vida diária e transtornos de comportamento) e suas demandas representam importantes estressores para os cuidadores levando a tensões como conflitos familiares e problemas econômicos. A carga gerada pela administração de cuidados expressa-se de maneiras mútiplas (emocionais, sociais, econômicas e físicas), que frequentemente se manifestam por altos níveis de problemas de saúde psicológica (ansiedade, depressão, insônia) e física (hipertensão arterial, propensão a infecções). Assim a carga de administrar cuidados é um conceito que integra o nível dos cuidados que o paciente requer com os sentimentos e as dificuldades dos cuidadores em provê-los. Algumas opções terapêuticas atuais para pacientes com DA mostram sucesso, principalmente a utilização de estratégias colinérgica e glutamatérgica, com indicação e utilidade que variam com o estágio da doença, com benefício (melhora, estabilização ou lentificação do declínio) em relação à cognição, função e comportamento. A eficácia do tratamento se relaciona com estabilização ou redução da carga dos cuidadores, oferecendo-lhes a possibilidade de uma melhora de qualidade de vida.

Alzheimer's disease (AD) is characterized by a progressive and relentless cognitive, functional and behavioral decline of the affected patients. As the impairment occurs a demand for help arises, and increases with the progression of the disease. The caregivers (relatives or professionals) come to participative in order to provide the needed assistance or care. They play an essential role in managing the daily life of AD patients under treatment, and are involved in virtually every aspect of dementia care. The patients' decline (cognitive, dependence in activities of daily living and behavioral disturbances) and their demands represent important stressors to the caregivers leading to strains like family conflicts and economic problems. The burden generated by caregiving is expressed in multiple ways (emotional, social, economical and physical), which frequently manifest themselves by high rates of psychological (anxiety, depression, insomnia) and physical (arterial hypertension, propensity to infections) health problems. Thus, caregiving burden is a concept that integrates the level of care the patients require with the caregivers's subjective and objective difficulties about providing it. Several present therapeutic options for patients with AD show some success, mainly the use of cholinergic and glutamatergic strategies, the indciation and utility depending on the stage of the disease, with benefit (improvement, stabilization or slowing of the decline) in relation to cognition, function and behavior. The efficacy of the treatment is related to stabilization or reduction of the burden, offering the caregivers the possibility of a better quality of life.

Anti-ganglioside antibodies and clinical outcome of patients with Guillain-Barré Syndrome in northeast Brazil.

OBJECTIVES: The goal of this study was to investigate the frequency of GM1 antibodies and to assess whether exposure to Campylobacter jejuni was associated with a distinct clinical variant of Guillain-Barré Syndrome (GBS) or disease outcome in Rio Grande do Norte, Brazil. MATERIAL AND METHODS: Forty-one patients with a presumed diagnosis of GBS were enrolled and prospectively studied between June 1994 and November 1999. RESULTS: Anti-GM1 was present in 51.2% (n = 21) of patients. The presence of anti-GM1 was significantly associated with acute axonal motor neuropathy when compared to acute inflammatory demyelinating polyneuropathy (P = 0.01). Patients with anti-GM1 antibodies presented distal muscle involvement and fewer sensory deficits. Age, time to nadir and ventilatory assistance were not associated with anti-GM1 antibodies. Eight out of 21 patients (32%) presented with anti-C. jejuni antibodies. Clinical features were similar for patients with GBS with positive and negative C. jejuni antibodies. Anti-GM1 antibodies were associated with C. jejuni infection (P = 0.0005). Presence of anti-GM1 and C. jejuni antibodies did not indicate a worse prognosis. CONCLUSION: Patients with GBS and anti-GM1 antibodies had more distal muscle weakness, fewer sensory deficits, more axonal degeneration and C. jejuni infection, but these findings were not associated with a worse prognosis.

SLO-2, a K+ channel with an unusual Cl- dependence.

The gating of different potassium channels depends on many diverse factors. We now report a unique example of a K+ channel with a Cl - dependence. The slo-2 gene was cloned from Caenorhabditis elegans and is widely expressed in both neurons and muscles; it was highly abundant, as suggested by its high representation in the C. elegans EST database. SLO-2, like its paralogue, SLO-1, was also dependent on Ca 2+. We show by site-directed mutagenesis that its requirements for both Cl- and Ca2+ are synergistic and associated with the same functional domain. SLO-2's dependence on Cl - implies that intracellular Cl- homeostasis may be important in regulating cellular excitability through this unusual K+ channel.

Expression of a functional Kir4 family inward rectifier K+ channel from a gene cloned from mouse liver.

1. A low stringency polymerase chain reaction (PCR) homology screening procedure was used to probe a mouse liver cDNA library to identify novel inward rectifier K+ channel genes. A single gene (mLV1) was identified that exhibited extensive sequence homology with previously cloned inward rectifier K+ channel genes. The mLV1 gene showed greatest sequence identity with genes belonging to the Kir4 subfamily. The amino acid sequence of mLV1 was 96 % identical to a Kir channel cloned from human kidney (hKir4.2), and approximately 60 % identical to the Kir4.1 channel cloned from human and rat, so that mLV1 was classified as mKir4.2. 2. Xenopus oocytes injected with cRNA encoding mKir4.2 displayed a large inwardly rectifying K+ current, while control oocytes injected with H2O displayed no similar K+ current. The current was blocked by Ba2+ and Cs+ in a voltage-dependent fashion and displayed inward rectification that was intermediate between that of the strong inward rectifier Kir2.1 and the weak inward rectifier Kir1.1. The current was weakly blocked by TEA in a voltage-independent fashion. 3. mKir4.2 current was subject to modulation by several distinct mechanisms. Intracellular acidification decreased mKir4.2 current in a reversible fashion, while activation of protein kinase C decreased mKir4.2 current in a manner that was not rapidly reversible. Incubation of oocytes in elevated [K+] produced a slowly developing enhancement of current. 4. Oocytes co-injected with cRNA for mKir4.2 and Kir5.1, a protein that does not form functional homomeric channels, displayed membrane currents with properties distinct from those expressing mKir4.2 alone. Co-injected oocytes displayed larger currents than mKir4.2, with novel kinetic properties and an increased sensitivity to Ba2+ block at negative potentials, suggesting that mKir4.2 forms functional heteromultimeric channels with Kir5.1, as has been shown for Kir4.1 5. These results demonstrate for the first time that a Kir4.2 channel gene product forms functional channels in Xenopus oocytes, that these Kir channels display novel properties, and that Kir4.2 subunits may be responsible for physiological modulation of functional Kir channels.

[Fluctuations in Guillain-Barré syndrome related with intravenous human immunoglobulin (triphasic course): case report]. / Síndrome de Guillain-Barré com flutuações relacionadas ao tratamento com imunoglobulina humana endovenosa. Curso trifásico. Relato de caso.

The authors report the case of a patient with severe Guillain-Barré syndrome (tetraplegic and on mechanical ventilation), that was treated with intravenous immunoglobulin (IVIg), 2 g/Kg. At first, there was clinical improvement, followed by clinical deterioration two weeks later. On the second course of IVIg there was, again, clinical improvement and then deterioration, 65 days after treatment. Finally, on the third course of treatment definitive recovery was achieved and no more relapses happened so far (three years after the treatment). The authors review the literature about fluctuations related to treatment with IVIg. Conclusions are that these patients should be closely observed during the first weeks after IVIg treatment, and that further studies are still necessary to elaborate alternative protocols on the prevention of these cases.

Respiratory function deterioration is not time-linked with upper-limb onset in amyotrophic lateral sclerosis.

INTRODUCTION: In amyotrophic lateral sclerosis (ALS), symptoms apparently spread following regional rules, and depending on the site of onset. We examined if respiratory function deterioration appears earlier or is more severe in patients with upper-limb onset. MATERIAL & METHODS: We compared the results of various pulmonary function tests (PFT) obtained at diagnosis depending on the site of onset in 49 ALS patients. In a longitudinal study, we compared the deterioration of forced vital capacity (FVC) in relation to the site of onset, and analyzed the time elapsed to reach values below 80% of predicted according to site of onset, and we compared the survival depending on the site of onset. RESULTS: No significant differences in PFT were found in the upper-limb onset group in any of the analysis performed. No differences in survival were detected in any disease onset group. CONCLUSION: Pulmonary function deterioration does not appear to be time-linked to arm onset in ALS.

[Sensory polyneuropathy and neural conduction block as an initial manifestation of polyarteritis nodosa]. / Polineuropatía sensitiva y bloqueo de conducción como primera manifestación de una poliarteritis nodosa.

Polyarteritis nodosa (PAN) is a systemic necrotising vasculitis which affects middle calibre arteries and which has a tendency to form aneurysms. It may appear as one of a great variety of clinical forms depending on the vascular territory afflicted. Almost any organ may be involved although the lung is usually unaffected. Neurological manifestations are very frequent in this disease (global incidence being around 80%), especially at the peripheral nervous system level. Multiple mononeuritis is the most usual manifestation classically associated with this type of vasculitis, but it may also appear as distal sensorimotor polyneuropathy, this being its most infrequent form of presentation. The presence of nerve conduction blocks has also been recently described, usually associated with demyelinating processes. However peripheral nerve affectation in vasculitis has its origins in small ischaemic infarcts in the sensorimotor conduction fibres. It may well be that segmentary demyelination and axonal degeneration reflect different levels of ischaemic damage.

Target tissues and innervation regulate the characteristics of K+ currents in chick ciliary ganglion neurons developing in situ.

The expression of appropriate ensembles of ionic channels is necessary for the differentiation and normal function of vertebrate neurons. Cell-cell interactions may regulate the expression and properties of ionic channels in embryonic neurons. Previous studies have shown that the expression of A-type K+ channels (IA) and Ca2+-activated K+ channels (lK[Ca]) is abnormal in chick ciliary ganglion neurons developing in vitro in the absence of normal cell-cell interactions. Other voltage-activated currents develop normally under these conditions. The present studies were designed to establish the role of the target tissues and the preganglionic innervation in regulating the expression of these currents in embryonic chick ciliary ganglion neurons developing in situ. Surgical manipulations were used to remove the developing optic vesicle, which contains the target tissues, the mid-dorsal region of the midbrain primordium, which contains the preganglionic nucleus, or both, all prior to the formation of the ciliary ganglion. IA and IK[Ca] were then examined in acutely isolated neurons that developed in ovo in the presence (OV+) or absence (OV-) of the normal target tissues, in the presence (MB+) or absence (MB-) of preganglionic innervation, and in the absence of both preganglionic innervation and target tissues (OV-/MB-). The amplitude of IA was unaffected by the operations. However, the activation and inactivation kinetics of IA were two- to threefold faster in OV- or OV-/MB- cells compared to neurons isolated from control OV+ ganglia at embryonic days 11-14 (E11-E14). There were no changes in the voltage dependence of activation or steady-state inactivation, or in the time course of recovery from inactivation. By contrast, neurons isolated from MB- ganglia expressed an IA with amplitude, voltage dependence, and kinetics that were indistinguishable from those of control MB+ and OV+ ganglia. Therefore, interactions with target tissues in the eye play a role in determining the characteristics of IA in developing ciliary ganglion neurons, whereas preganglionic innervation does not. Furthermore, the amplitude of IK[Ca] was reduced by 90-100% in OV-, MB-, and OV-/MB- neurons isolated at E12-E14 as compared to MB+ and OV+ controls. Voltage-activated Ca2+ currents were present at normal amplitudes in all of these neurons. Thus, the expression of IK[Ca] in chick ciliary ganglion neurons is regulated by both target tissue interactions and preganglionic innervation. Therefore, cell-cell interactions are necessary for the expression of a normal ensemble of ionic channels in chick ciliary ganglion neurons developing in situ.