Rapid Feedback Regulation of Synaptic Efficacy During High-Frequency Activity at the Drosophila Larval Neuromuscular Junction.

Rapid feedback regulation of synaptic efficacy during high-frequency activity at the Drosophila larval neuromuscular junction.

Proc Natl Acad Sci U S A. 2013 May 14;
Kauwe G, Isacoff EY

High-frequency firing of neurons depresses transmitter release at many synapses. At the glutamatergic synapse of the Drosophila larval neuromuscular junction, we find that presynaptic depression is modulated by postsynaptic ionotropic glutamate receptor (iGluR) activity. Although basal release at low frequency was insensitive to postsynaptic iGluR activity, recovery from depression elicited by high-frequency presynaptic trains decreased with partial block of native iGluRs. Moreover, recovery from depression increased with optical activation of the light-gated mammalian iGluR6 (LiGluR) expressed postsynaptically. The enhancement of recovery from depression occurred within 2 min of optical activation of LiGluR and persisted for minutes after optical deactivation. This effect depended on cAMP-dependent presynaptic recruitment of vesicles from the reserve pool. Our findings reveal a unique dimension to postsynaptic iGluR activity: fast retrograde signaling that preserves transmission efficacy during high-frequency presynaptic firing. HubMed – depression

Attachment styles and affect regulation among outpatients with schizophrenia: Relationships to symptomatology and emotional distress.

Psychol Psychother. 2013 Jun; 86(2): 164-182
Ponizovsky AM, Vitenberg E, Baumgarten-Katz I, Grinshpoon A

Objectives.?Using the model of activation and dynamics of the attachment system (Shaver & Mikulincer, 2002) and dynamic stress-vulnerability models of psychosis (Ingmar & Luxton, 2005) as the analytical frameworks, the authors tested the hypothesis that the insecure attachment styles are differentially associated with the severity of psychopathological symptoms and emotional distress among outpatients with International Classification of Diseases, Tenth edition (ICD-10) diagnosis of schizophrenia. Methods.?Attachment styles were identified using the Relationship Questionnaire (Bartholomew & Horowitz, 1991) among 100 outpatients with an ICD-10 schizophrenia diagnosis. Current symptom severity was measured by the Positive and Negative Syndromes Scale (Kay, Fiszbein, & Opler, 1987) and emotional distress by the General Health Questionnaire (Goldberg & Williams, 1988). Univariate and multivariate analyses were performed to test the hypotheses. Results.?The preoccupied and fearful-avoidant attachment patterns were associated with higher scores of psychotic (delusions, suspiciousness/persecution, and hallucinatory behaviour) and affective (anxiety, tension, guilt feeling, and depression) symptoms, whereas the dismissing-avoidant style was associated with only anxiety. All the insecure attachment styles were associated with elevated emotional distress. Conclusions.?The findings support the hypothesis of a predisposing role of the preoccupied and fearful-avoidant styles in psychotic symptom formation and call for cognitive interpersonal interventions geared to reduce symptom and emotional distress severity. PRACTITIONER POINTS: •? Knowledge of certain attachment style would be valuable for: -? individual prognosis predicting to what extent the patient with particular attachment style would be amenable to different forms of treatment; -? enhancement of the therapeutic alliance and anticipating the types of alliance ruptures that might be diverse in different attachment styles; -? prediction of recovery style, engagement with services, and hence therapeutic outcome. •? Cognitive-behavioural techniques aimed at reducing sensitivity to interpersonal stress, alleviating emotional distress, and promoting well-being could be beneficiary, in particular, for patients with the preoccupied and fearful-avoidant attachment patterns that showed themselves most symptomatic and distressed. HubMed – depression

The many faces of alpha-synuclein mutations.

Mov Disord. 2013 May 14;
Kasten M, Klein C

Since the first description of alpha-synuclein (SNCA) mutations in 1997, this gene has probably become the most intensely investigated one associated with monogenic Parkinson disease (PD). Prompted by the finding of a novel SNCA mutation, H50Q, we systematically explored the 145 published SNCA mutation carriers for a possible mutation (type)-specific clinical expression, which appears to be rather unique to SNCA mutations compared with other PD genes. The A53T mutation is associated with an approximately 10-year earlier age at onset than the other 3 known missense mutations, including the new H50Q mutation. Similarly, SNCA triplication carriers have an approximately 10-year earlier onset and a more rapid disease course than duplication carriers, who, overall closely resemble patients with idiopathic PD. Furthermore, higher order SNCA multiplications are associated with additional neurologic features, such as myoclonus. For the nonmotor features, their mere frequency appears less striking than their severity, with an early age of onset of depression or dementia, suicidal ideation, and multimodal hallucinations. We conclude that, (1) although SNCA mutations are a rare cause of PD, it remains worth testing for new mutations in this gene; (2) a differential view of SNCA mutations and variants may allow important pathophysiologic inferences even beyond monogenic PD and is warranted in the context of clinical counseling. © 2013 Movement Disorder Society. HubMed – depression

Blockade of BDNF signaling turns chemically-induced long-term potentiation into long-term depression.

Hippocampus. 2013 May 15;
Montalbano A, Baj G, Papadia D, Tongiorgi E, Sciancalepore M

Long-term potentiation (LTP) is accompanied by increased spine density and dimensions triggered by signaling cascades involving activation of the neurotrophin brain-derived neurotrophic factor (BDNF) and cytoskeleton remodelling. Chemically-induced long-term potentiation (c-LTP) is a widely used cellular model of plasticity whose effects on spines have been poorly investigated. We induced c-LTP by bath-application of the N-methyl-D-aspartate receptor (NMDAR) co-agonist glycine or by the K(+) channel blocker tetraethylammonium (TEA) chloride in cultured hippocampal neurons and compared the changes in dendritic spines induced by the two models of c-LTP and determined if they depend on BDNF/TrkB signaling. We found that both TEA and glycine induced a significant increase in stubby spine density in primary and secondary apical dendrites, whereas a specific increase in mushroom spine density was observed upon TEA application only in primary dendrites. Both TEA and glycine increased BDNF levels and the blockade of tropomyosin-receptor-kinase receptors (TrkRs) by the non selective tyrosine kinase inhibitor K-252a or the selective allosteric TrkB receptor (TrkBR) inhibitor ANA-12, abolished the c-LTP-induced increase in spine density. Surprisingly, a blockade of TrkBRs did not change basal spontaneous glutamatergic transmission but completely changed the synaptic plasticity induced by c-LTP, provoking a shift from a long-term increase to a long-term depression (LTD) in miniature excitatory postsynaptic current (mEPSC) frequency. In conclusion, these results suggest that BDNF/TrkB signaling is necessary for c-LTP-induced plasticity in hippocampal neurons and its blockade leads to a switch of c-LTP into chemical-LTD (c-LTD). © 2013 Wiley Periodicals, Inc. HubMed – depression