Neuromodulator release in neurons requires two functionally redundant calcium sensors.

Neuropeptides and neurotrophic factors secreted from dense core vesicles (DCVs) control many brain functions, but the calcium sensors that trigger their secretion remain unknown. Here, we show that in mouse hippocampal neurons, DCV fusion is strongly and equally reduced in synaptotagmin-1 (Syt1)- or Syt7-deficient neurons, but combined Syt1/Syt7 deficiency did not reduce fusion further. Cross-rescue, expression of Syt1 in Syt7-deficient neurons, or vice versa, completely restored fusion.

Dysregulated Prefrontal Cortex Inhibition in Prepubescent and Adolescent Fragile X Mouse Model.

Changes in excitation and inhibition are associated with the pathobiology of neurodevelopmental disorders of intellectual disability and autism and are widely described in Fragile X syndrome (FXS). In the prefrontal cortex (PFC), essential for cognitive processing, excitatory connectivity and plasticity are found altered in the FXS mouse model, however, little is known about the state of inhibition. To that end, we investigated GABAergic signaling in the Fragile X Mental Retardation 1 (FMR1) knock out (Fmr1-KO) mouse medial PFC (mPFC).

Munc13-1 and Munc18-1 together prevent NSF-dependent de-priming of synaptic vesicles.

Synaptic transmission requires a stable pool of release-ready (primed) vesicles. Here we show that two molecules involved in SNARE-complex assembly, Munc13-1 and Munc18-1, together stabilize release-ready vesicles by preventing de-priming. Replacing neuronal Munc18-1 by a non-neuronal isoform Munc18-2 (Munc18-1/2SWAP) supports activity-dependent priming, but primed vesicles fall back into a non-releasable state (de-prime) within seconds.

The role of chromatin repressive marks in cognition and disease: A focus on the repressive complex GLP/G9a.

Histone post-translational modifications are key epigenetic processes controlling the regulation of gene transcription. In recent years it has become apparent that chromatin modifications contribute to cognition through the modulation of gene expression required for the expression and consolidation of memories. In this review, we focus on the role of histone methylation in the nervous system.