The formation and remodeling of mossy fiber-CA3 pyramidal cell synapses in the stratum lucidum of the hippocampus are implicated in the cellular basis of learning and memory. Afadin and its binding cell adhesion molecules, nectin-1 and nectin-3, together with N-cadherin, are concentrated at puncta adherentia junctions (PAJs) in these synapses. Here, we investigated the roles of afadin in PAJ formation and presynaptic differentiation in mossy fiber-CA3 pyramidal cell synapses. At these synapses in the mice in which the afadin gene was conditionally inactivated before synaptogenesis by using nestin-Cre mice, the immunofluorescence signals for the PAJ components, nectin-1, nectin-3 and N-cadherin, disappeared almost completely, while those for the presynaptic components, VGLUT1 and bassoon, were markedly decreased. In addition, these signals were significantly decreased in cultured afadin-deficient hippocampal neurons. Furthermore, the interevent interval of miniature excitatory postsynaptic currents was prolonged in the cultured afadin-deficient hippocampal neurons compared with control neurons, indicating that presynaptic functions were suppressed or a number of synapse was reduced in the afadin-deficient neurons. Analyses of presynaptic vesicle recycling and paired recordings revealed that the cultured afadin-deficient neurons showed impaired presynaptic functions. These results indicate that afadin regulates both PAJ formation and presynaptic differentiation in most mossy fiber-CA3 pyramidal cell synapses, while in a considerable population of these neurons, afadin regulates only PAJ formation but not presynaptic differentiation.

No abstract

Help seeking is predictor of prognosis in the first episode of psychotic disorders. Caregivers play a key role in deciding from whom to seek help. In Indonesia, caregivers often seek help from alternative healers first and health professionals later, which is believed to result in delayed psychiatric treatment and risk for poor prognosis. This study measured the duration of untreated psychosis (DUP) in a sample of 100 persons being treated for a first episode of psychosis in Yogyakarta, Indonesia. We attempted to measure and determine associations among caregivers’ explanatory models, help seeking behaviors and DUP in this sample. The data were then statistically analyzed. The DUP for this population was very short. Most caregivers were parents or spouses (72 and 12%, respectively) and at the time of being interviewed described medical explanatory models for the psychotic symptoms (60%). A majority described having visited traditional/alternative healers prior to their visit to health professionals (67%). Despite this, the DUP was not significantly different for these two groups. Thus, first resort to traditional/alternative healers did not predict prolonged DUP. Further study with a larger sample is needed to better understand the relationship between care seeking, use of alternative healers and DUP in Indonesia.