PRV has been found to have about 43% efficacy for the first two years in this population. It is possible that the vaccine therefore does not reduce the overall burden of diarrheal illness sufficiently CCI-779 ic50 to affect indicators of malnutrition. Alternatively, it is possible that rotavirus illness does not result in long-term deficits in child growth. Shigella and ETEC are the pathogens for which there is the most evidence of an impact on long-term growth [7] and [16]. It is interesting that there appears to be reduced odds of being severely malnourished at the

March 2009 visit among the vaccine recipients, but with such small numbers it is difficult to inhibitors determine if this is a true effect of the vaccine or simply a random finding. It is possible that rotavirus impacts short-term growth during the period of peak rotavirus incidence

in the under-24 month age group, but by two to three years of age the children who were sick with an episode of rotavirus gastroenteritis have had catch-up growth. This malnutrition assessment was conducted among a cohort of children enrolled in a vaccine trial. A wealth of additional information is available on the population residing in the Matlab field site due to its Panobinostat research buy participation in the HDSS for over 44 years, making it an ideal place to conduct this type of post hoc analysis of a trial data set. However, birth weight was only available for about one third of the children, and weight was only assessed after the full vaccine series at two time points and height at only one time point. For the children enrolled earliest in the trial there were no weight measurements between approximately four months and 26 months of age, which misses an important period of both growth and diarrhea 17-DMAG (Alvespimycin) HCl incidence. It would have been interesting to examine growth patterns in vaccine versus placebo recipients more frequently, such as each month, to gain a better understanding of how the vaccine or episodes of rotavirus gastroenteritis may affect short-term growth. Another potential limitation of this study is that by virtue of being a highly studied population the children

enrolled in the trial may have had improved access to care in both the vaccine and placebo groups, thereby improving malnutrition outcomes in both groups and possibly diluting any apparent impact of the vaccine on growth. Additionally, children residing in Matlab may not be entirely representative of children in Bangladesh or other developing country settings. In general, these children have a higher EPI vaccination coverage rate, a lower rate of severe malnutrition, and better access to health care with a subsequently higher health care utilization rate than children in many other developing country settings. However, the children in this population are still malnourished by any international standard, and the findings from this study should be broadly applicable to similar settings.

With the launch of the GAVI Alliance in 2000, Libraries Vaccine uptake improved and has continued to improve in developing Akt signaling pathway countries. Vaccination rates against the

six key diseases have increased from around 20% in 1980 to approximately 80% in 2009, and the burden of vaccine-preventable diseases has dropped dramatically [2]. However, beyond the six diseases targeted initially, are a range of infectious diseases that continue to cause high levels of morbidity and mortality in several parts of the world for which vaccines exist or can be developed, if resources are available. Particularly for countries like India, where respiratory infection and diarrhoea each contribute >10% to the mortality burden in young children [3], there is a need for safe, effective and affordable

vaccines for use in the public health system. Investments in vaccine development require an appetite for risk taking and long term investment, given that failures are to be expected in translating academic success to marketable products. An outstanding example of the new world paradigm in affordable, safe and effective vaccine development is the Rotavac vaccine. As with most vaccine candidates, the story began with an academic institution, the All India institute of Medical CHIR-99021 nmr Sciences (AIIMS), where in the 1980s, M.K. Bhan noticed that a strain of rotavirus produced asymptomatic infections in neonates in the nursery and protected them from subsequent disease. He started an informal joint research program with Roger Glass, who worked initially in Bangladesh and later at the Centers for Disease Control and Prevention (CDC) in Atlanta and at the National Institutes of Health (NIH). In 1989–1990, they attracted research support from the Department of Biotechnology (DBT), Ministry of Science and Technology, Government of India and NIH, under the joint Indo-US Vaccine Action Program (VAP),

and went to work on further characterization of this unusual neonatal strain, now known as 116E. The isothipendyl 116E strain was identified to be a human bovine reassortant, with a bovine derived surface protein. Almost in parallel, another bovine-human reassortant infecting neonates, I321, was described from Bangalore, by Durga Rao of the Indian Institute of Science (IISc) working with Harry Greenberg from Stanford University [4]. The NIH contracted with DynCorp to produce clinical-grade pilot lots of the vaccines in 1997 and evaluate those lots in American adults and children prior to shipping them to India. In 1998, the Indo-US VAP solicited commercial partners in India for the next stage of development and identified Bharat Biotech International Ltd. (BBIL), a Hyderabad-based vaccine manufacturing company, to develop both vaccine candidates.

Drugs of abuse are thought to produce this aberrant and maladaptive behavioral state by hijacking normal neuronal processes involved in motivated behavior, reinforcement, and plasticity.79 From the perspective of multiple memory systems, there may be multiple pathways to the addicted state. Maladaptive drug-associated

patterns of behavior may derive, for example, Inhibitors,research,lifescience,medical from enhanced motivational power of the drug or reduced motivational power of other, naturalistic rewards, or from an increased reliance on inflexible habitual patterns of learned behavior or a reduced capacity of more flexible control systems. This view has recently been developed at length in an enumeration Inhibitors,research,lifescience,medical of 10 major vulnerabilities in the mechanisms underlying normal decision-making, exploitation of any one of which by a drug may lead to an addicted state.6 Addiction is characterized by enhanced use of rigid habit-like patterns of drug-associated behavior. One can envision such a pattern deriving from enhancement of the habit learning system

described above, through repeated drug BKM120 chemical structure exposure and reinforcement of acquisition and consumption-related behaviors.80 However, in light of the multiple memory systems model, one can also envision over-reliance Inhibitors,research,lifescience,medical on habitual modes of learned behavior deriving from impairment or inhibition of potentially competing learning systems and behaviors. A shift from habits to more flexible forms of behavior is thought to require top-down regulation of action selection by prefrontal cortex (eg, Inhibitors,research,lifescience,medical ref 81). Inhibition or dysfunction of this cortical capacity may inappropriately leave

behavior in a habit-guided mode, predisposing towards the inflexible behavior patterns that characterize the addicted state.6 There is evidence that alcohol, amphetamine, and cocaine can all induce such a bias towards habitual control of behavior and a reduced capacity to recruit the prefrontal cortex to regulate it.82,83 OCD is also characterized Inhibitors,research,lifescience,medical by maladaptive inflexible patterns of behavior.84 Increased activation of the basal ganglia circuitry is well established in this condition, as is pathology of the prefrontal cortex.85 This raises the question of whether dysregulation of striatum-dependent habit learning, MTMR9 or the balance between habit learning and more flexible forms of behavioral regulation, may contribute to OCD, as well as to drug addiction. Recent work suggests just such a dysregulation. Subjects were trained in behavioral paradigms in which their choices could be guided by an outcome-dependent strategy or a more automatic, habitual strategy. With overtraining, individuals with OCD showed a greater tendency to rely on inflexible habit-like behavioral routines.

The results of this study confirm some previous studies but stand in contrast to others. Some studies on coherence (e.g., Besthorn et al. 1994) have demonstrated that the δ band could not reflect the difference between elderly people and MCI patience, but the other research (Huang et al. 2000) obtained adverse findings. In this study, we found no significant difference in the CMI data of the δ band between elderly and MCI

groups, which supports the results found in the previous study (Kowalski et al. 2001). Additionally, past studies have suggested that the δ band of the frontal lobe could discriminate between MCI patients Inhibitors,research,lifescience,medical and healthy elders (Penttilä et al. 1985; Coben et al. 1990; Schreiter-Gasser et al. 1993); however, the topographic map generated from this study showed that only the electrodes near the parietal and occipital lobes displayed significant differences between the elderly and MCI groups in the δ band. These inconsistent findings might be caused by the different conditions under which the data were collected Inhibitors,research,lifescience,medical and the authors’ definition of the δ band. First, in this study, we analyzed

task-related brain oscillations by using mutual information while a resting awake condition was applied in the previous studies. The greater attention paid to respond to the task may cause the different oscillatory activity in the brain Inhibitors,research,lifescience,medical of the selleck chemical participant (Phillips and Andrés 2010). In the previous study under resting conditions, Stam et al. (2003) showed that loss of β-band synchronization Inhibitors,research,lifescience,medical occurs early in mildly affected AD patients and correlates with cognitive impairment. In our study, the older group with mild AD had significantly decreased functional connectivity of the brain when attempting to respond to the target stimuli, especially in θ band, providing further evidence that as disease progresses there is less efficient processing (Grady 1998). These Inhibitors,research,lifescience,medical disease-related deficits in efficiency correlated with the reduced connections in our study, suggesting severe impairment in the information processing ability. This would explain this group’s longer mean reaction time and a lower correct response. Furthermore,

many studies have suggested the importance GPX6 of the θ band for discriminating among normal elders, MCI, and AD patients (Kowalski et al. 2001; Osipova 2003; Pijnenburga et al. 2004), and this was supported by the results of this study. Additionally, this study suggested that θ band reflects not only the difference in disease-related changes but also the difference in age-related changes, especially in the parietal and occipital lobe. Some studies have also indicated that the α band was significantly different between normal elderly and AD patients in power (Hogan et al. 2003; Moretti 2004) and in connectivity (Pijnenburga et al. 2004). Unexpectedly, we did not find any statistically significant differences in the α band between the elderly group and the MCI group.

The bathing solution was then switched back to ASW and a third application of agonist was made to study washout of the antagonist. When L-Glu and D-Asp currents were studied in the same cell, the agonist pipette was changed after washout and this protocol was repeated. Agonist order was alternated with each cell studied. For Gly and D-Ser experiments, the agonist pipette was changed from one containing D-Asp to one containing D-Asp + Gly or D-Asp + D-Ser after control currents for D-Asp were recorded. Because the noncompetitive antagonists

memantine and MK-801 require Inhibitors,research,lifescience,medical channel opening for block to occur, two applications of agonist were made during antagonist exposure before washout, and each application was compared to the control. For analysis, D-Asp and L-Glu current amplitudes in pharmacological agents Inhibitors,research,lifescience,medical were normalized to the initial control current. Unless otherwise noted, pharmacological experiments were performed at −30 mV, approximately the resting potential for cultured BSC neurons (Fieber et al. 2010). Cyclothiazide (CTZ) experiments were performed both under the conditions described above and under conditions designed to investigate

block of desensitization. For desensitization Inhibitors,research,lifescience,medical experiments, cells were exposed to repeated applications of D-Asp both in ASW and in ASW + CTZ. Three applications of D-Asp were made: an initial, control application (t0), an application at t10=t0+ 10 sec, and a final application at t20=t0+ 20 sec. Currents were normalized to the control current for each condition. Solutions Unless noted, all reagents were from Sigma-Aldrich (St. Louis, MO). Control extracellular solution consisted of ASW. Inhibitors,research,lifescience,medical Control intracellular solutions contained (mM) 458 KCl, 2.9 CaCl2 (2 H2O), 2.5 MgCl2 (6 H2O), 5 Na2ATP, 1 EGTA, and 40 HEPES-KOH, pH 7.4. For pharmacological experiments, competitive and noncompetitive Inhibitors,research,lifescience,medical antagonists of L-Glu receptors or Cl− channel blocker were

diluted in ASW from frozen stocks. The protocol entailed application of blocker to cells after control records Casein kinase 1 in response to D-Asp or L-Glu were made, then washout of any blocker effects. Blocker concentrations were selected based on prior experiments in Aplysia (Dale and Rapamycin order Kandel 1993; Armitage and Siegelbaum 1998; Klein et al. 2000; Chitwood et al. 2001; Antzoulatos et al. 2003; Jin and Hawkins 2003; Collado et al. 2007). Stocks of the following drugs were made in water, then diluted in ASW at 1:50 or greater, for their working concentrations shown in parentheses: 4-acetamido-4′-isothiocyanato-2,2′-stilbenedisulfonic acid disodium (SITS; 100 μM), DL-kynurenic acid (kynurenate; 1 mM), DL-2-amino-5-phosphonopentanoic acid (APV; 100 μM), memantine hydrochloride (Tocris, St.

By 2004, the number of cases increased 30% (4). In the HIV positive population the rate of anal cancer increased from 19 to 78.2 per 100,000 person-years (4). 80% of anal cancers involve the anal canal with the majority being squamous cell carcinomas (5). One major factor implicated in the increase in anal cancer from the 1990’s to now is the HIV virus. It is known that the incidence of anal cancer is 40 to 80 times higher in the HIV+ population. HIV+ patients tend to get anal cancer at a younger age, are more frequently men, and more Inhibitors,research,lifescience,medical frequently homosexual men who practice RAI (6). Cancer has been

associated with HIV since the first reports of AIDS in the 1980s. Three different cancers are AIDS defining: Kaposi’s sarcoma, Non-Hodgkin’s Temsirolimus research buy lymphoma (B cell), and invasive cervical cancer. Anal cancer is part of a group of non-AIDS defining cancers which include Hodgkin’s lymphoma, lung adenocarcinoma, hepatocellular carcinoma, oropharyngeal carcinoma, kidney carcinoma, Inhibitors,research,lifescience,medical melanoma, and conjunctival carcinoma (primarily sub-Saharan Africa) (4). These non AIDS defining cancers have a two to three fold higher incidence in the HIV+ population (7). There are other factors implicated in the etiology of anal cancer in addition to HIV. Anal cancer, similar to cervical cancer, is known to be associated with the HPV virus, sexual behavior, and tobacco use. HPV-16 is the most prevalent subtype

associated Inhibitors,research,lifescience,medical with anal cancer and precancerous lesions followed by HPV-33 and HPV-39 (8). HPV is known to play a definitive role in the development of anal and cervical squamous cell cancer. HIV+ Inhibitors,research,lifescience,medical patients

are more likely to be co-infected with HPV, approximately 2 to 6 fold higher probably secondary to similar risk factors Inhibitors,research,lifescience,medical such as sexual behavior. In the HIV+ population, men have an increased relative risk of developing anal cancer compared to women (37.9 versus 6.8) (9). That risk increases depending on sexual practices. Men who has sex with men (MSM) is associated with a higher incidence of anal cancer. HIV+ MSM have doubled the rate of anal cancer as compared to HIV- MSM (70-100 per 100,000 versus 35 per 100,000) (10). HPV infection persists in HIV+ patients compared to immunocompetent patients. HIV+ patients are seven times more likely to have persistent HPV infection. There is a suggestion that immunosuppression in HIV+ patients prevents clearance of HPV and subsequent higher risk of developing anal cancer. else The discovery and subsequent use of antiretroviral drugs (HAART) in the late 1990’s has led to a significant decrease in AIDS defining cancers. In the U.S, recommendations set forth by the United States Department of Health and Human Services for initiating HAART treatment include: all HIV positive patients who present with AIDS defining illness, and HIV positive patients with CD4<200 (cluster of differentiation 4) (11).

To prevent the physiological rise in plasma FFA levels that accompany fasting in the control arm, nicotinic acid (NA) was given as Acipimox 250-mg tablets (Olbetam™, Pharmacia, U.K.) (Chen et al. 1999); one dose following the baseline scan, and a further dose 2 h later. Cognitive tests Executive function, cognitive speed and attention were tested using the Trail making A+B test, the dual tasks test (Baddeley Inhibitors,research,lifescience,medical et al. 1997), including the Wechsler Adult Intelligence Scale – Revised (WAIS-R) digit span forwards and backwards (Wechsler 1981), Stroop color word and interference test (Trenerry et al. 1989), and the pattern and letter comparison speed test (Salthouse and Babcock 1991). Visual recall

was tested using the Doors B test from the Doors and People test (Thames Valley Testing Company). Verbal recall was tested using the Hopkins Verbal Learning Inhibitors,research,lifescience,medical Test – Revised (forms 1, 3, 4, and 6) with delayed recall (Brandt 1991) and the Paragraph Recall Test (Rivermead Behavioral test, Versions A, B, C, and D) (Wilson et al. 1985). The delayed recall parts for both verbal recall tests were performed while the subjects were in the scanner. Standardized

meal To prevent the influence of postprandial pulses of insulin, subjects were required to fast for the duration of the visit. In order to limit the physiological responses to prolonged fasting including lipolysis and mild ketosis, a small standardized meal was given following the baseline MRS scan. This was Inhibitors,research,lifescience,medical to provide Inhibitors,research,lifescience,medical enough carbohydrate to stimulate a small pulse of circulating insulin to prevent ketosis. This small amount of insulin would have dissipated within 2 h, and therefore not interfere with assessments 4 h later. Based on data from Juntunen et al. (2002) in healthy MK-2206 price volunteers, a 50-g carbohydrate load, in the form of a slice of bread, stimulated a rise in plasma insulin that returned to fasting levels within 3 h. For this study, a smaller carbohydrate load was given. Subjects were given a waffle, a low-fat yogurt, and Inhibitors,research,lifescience,medical a low-sugar fruit juice drink (total carbohydrate 16.3 g, fat 7.3 g, protein 6.2 g). Following

this meal, the intervention was started and subjects were kept fasting for the remainder of the study, but were allowed to drink water freely. Energetics The neuropsychological tasks used in this study stimulate hippocampal activation so 31P MRS data were acquired to assess hippocampal energetics. Scans were performed using a 3 Tesla system (Siemens Trio, Erlangen, Germany) using a dedicated dual tuned 1H/31P quadrature Tolmetin birdcage head coil (Rapid Biomedical GmbH, Germany). Proton images for localization and anatomical structural images were obtained using a standard Magnetization Prepared-Rapid Gradient Echo (MP-RAGE) sequence. Spectral data were acquired using a multivoxel acquisition-weighted chemical shift imaging (3D AW-CSI) sequence (Pohmann and von Kienlin 2001). Nuclear overhauser enhancement was employed on all acquisitions to increase signal strength (Li et al.

86 Reported lifetime gambling increased for both males and females from 1975 to 1998; however, the increase was much larger for women, from 61 % to 83%, than for men, from 75% to 88%, resulting in a decrease in the sex

MLN2238 concentration difference in gambling.84 Yet, past-year gambling remains unchanged for men, 68% versus 67%, while it increased slightly for women from 55% to 60%, resulting in only a slight decrease in the sex difference.84 Legalized gambling has led to more gambling opportunities and new forms87; the explosion seems likely to account for the decrease in the sex difference in social gambling, yet the sex difference in PG has remained. This sex difference in PG, with males predominating Inhibitors,research,lifescience,medical in both clinical and population samples, is in contrast to the sex parity often found in OCD and BDD. Gender differences have also been reported in the onset and course of PG. In males, PG usually begins in adolescence88-90 or young adulthood,90 and may remain undiagnosed Inhibitors,research,lifescience,medical for years. When male PG patients are first diagnosed, they often present with a 20- to 30-year gambling history, with gradual development of PG. In some cases, PG suddenly

occurs in male social Inhibitors,research,lifescience,medical gamblers following a significant loss, stressor, or increased exposure.91 In contrast, PG in females is more likely to occur later in life and delay in seeking treatment is approximately Inhibitors,research,lifescience,medical 3 years. Thus, as a result of the differences in onset and duration, female PG patients generally have a better prognosis than male PG patients.91 Male and female gamblers

differ in the types of gambling they prefer, with men more likely to bet on sporting events, cards, and at the track, while women prefer slot machines and bingo.90 It is unknown whether males and females with PG represent truly different sub-groups with differences in Inhibitors,research,lifescience,medical pathophysiology and treatment response. We recently completed an FDG (fluorodeoxyglucose) positron emission tomography (PET) study in PG. The scans were acquired while the patients were engaged in a computerized gambling task either for a monetary reward GBA3 or for computer points only. Gambling for monetary reward blackjack was associated with significantly higher relative metabolic rate in the primary visual cortex, the cingulate gyrus, the putamen, and prefrontal areas. We would expect normal subjects to show activation in both monetary and pure gambling conditions, but a study including both PG and social gamblers has not yet been done. In addition to demonstrating that the unique aspects of monetary reward compared with pure gambling are reflected in the activation patterns similarly to past imaging studies of reward strategy planning,92 the results arc generally consistent with symptom-provocation studies in OCD. A possible selective efficacy of SRIs has been demonstrated in PG.

Besides, CHAT-labeled processes were sharper and shorter from 2 months of age (data not shown). We performed Western blot analysis and quantitative PCR to

analyze the expression level of ChAT protein and transcript, respectively, in lumbar sections from 1 and 3 month of age animals. We observed no significant differences at protein level at any time point between transgenic and Inhibitors,research,lifescience,medical control littermate animals; however, it was a marked reduction in the transcript of ChAT in the 1-month-age SOD1G93A mice (Fig. 1D and E). Figure 1 Early transient ChAT reduction in spinal MNs of transgenic SOD1 mice. (A) PI3K assay immunofluorescent microphotographs showing ChAT content in MNs at the L4–L5 spinal cord ventral horn of nontransgenic wild-type (WT) littermates or transgenic SOD1 mice … In order to investigate whether it was a general effect affecting the production of ChAT independently of the type of neuron or it was specific for MNs, we analyzed also the cholinergic interneurons present in Inhibitors,research,lifescience,medical lamina X that innervate MNs at the lumbar level. We observed that cholinergic interneurons presented also a reduction in ChAT content within their soma (61 ± 8%, n = 13) at 1 month of age, which increased at 2 months but it was still significantly lower than in WT mice (Fig.

Inhibitors,research,lifescience,medical 2). Figure 2 Cholinergic interneurons have early decrease of ChAT in the ALS mouse model. (A) Representative immunofluorescent microphotographs showing ChAT labeling in cholinergic interneurons (green) contrasted with cellular Inhibitors,research,lifescience,medical nuclear staining with DAPI (blue), near … These results indicated that there is a generalized, early, and transient reduction in ChAT

content in the soma and Inhibitors,research,lifescience,medical processes of cholinergic neurons, both MNs and interneurons of the spinal cord, in SOD1G93A mice at 30 days of age. This decline persists in the processes but not in the soma of MNs in older transgenic mice. Quantitation of ChAT-positive boutons As mentioned, ChAT was also observed in cholinergic terminals that contact onto spinal Dichloromethane dehalogenase MNs, which belong to either recurrent axonal collaterals of interconnections between MNs (Cullheim et al. 1977) (Lagerback et al. 1981) or innervation by cholinergic interneurons. These inputs influence the MN excitatory and inhibitory balance, which is altered in ALS. Those terminals apposing MN somata are named C-boutons and represent one of the largest terminals around their perimeter (3–7 μm in cat) (Arvidsson et al. 1997). In order to analyze the ChAT content in these terminals, we counted ChAT-labeled boutons apposed to MNs at L4–L5 in WT and SOD1G93A mice at 1 and 2 months of age. We found a marked decrease (76%) in SOD1G93A mice already from 1 month of age (Fig. 3). No statistical differences were found between nontransgenic animals of 1 or 2 months of age.

Evidence supporting this schema comes from both humans and nonhuman primates.203,208-210 Due to maintained segregation along each of these corticobasal ganglia-thalamocortical circuits, there is limited direct communication among the separate functional domains, except by way of GSK1120212 cell line corticocortical interactions. While essentially the entire cortical mantle is mapped topographically onto the striatum210 – which is often considered the ”input“ portion

Inhibitors,research,lifescience,medical of the basal ganglia – the cortically directed signals from the basal ganglia, output nuclei (internal pallidum and SNr) are returned exclusively to foci within the frontal lobe (after first passing through the corresponding portions of the thalamus.) Because of the parallel organization of these circuits, the operations performed at corresponding stations (eg, striatum, Inhibitors,research,lifescience,medical pallidum, thalamus) are predicted to be similar. Accordingly, clarification of how the motor circuit, operates may be relevant to our understanding of how the other circuits might, function. On the basis of what, is already known or suspected about the functions subserved by each circuit in the normal state, multiple studies have begun to address predictions that some of those

functions may be lost in PD due to impaired information processing Inhibitors,research,lifescience,medical caused by depletion of striatal DA (Table III).193,209,211-223 The pathophysiology of motor dysfunction in PD has been clarified recently by advances on several fronts, including physiological studies in animal models of parkinsonism, neuronal recordings and DBS in humans with PD, functional brain imaging in PD patients, and computational modeling Inhibitors,research,lifescience,medical of neuronal

circuitry. To understand these developments, it is useful to consider the functional Inhibitors,research,lifescience,medical organization of basal ganglia motor circuitry in some detail. Role of DA in basal ganglia circuitry DA has a pivotal and extremely complex role in controlling the flow of information through the basal ganglia. SNc provides dopaminergic innervation to the entire neostriatum, including the motor territory within the putamen. Through an intricate web of presynaptic and postsynaptic connections, nigrostriatal neurons modulate the responsiveness of striatal projection neurons – medium spiny neurons (MSNs) – to converging glutamatergic inputs from cortex and thalamus and local Parvulin GABAergic feedback from neighboring MSNs. The nigrostriatal pathway provides an extraordinarily dense dopaminergic input, to each MSN, comparable in magnitude to the 5000 or so corticostriatal synapses that individual MSNs receive.224-226 Dopaminergic terminals from SNc form postsynaptic axospinous and axodendritic synapses with MSNs, and presynaptic axoaxonic synapses with the terminal boutons of corticostriatal fibers, which synapse mainly on the spines of MSNs.