1612693714603.jpeg

Publications

Selected Publications from my work in the field of Neuroscience

Imaginary_Cover_Art_OK2018_edited.jpg

Reactivation of recall-induced neurons contributes to remote fear memory attenuation

Ossama Khalaf, Siegfried Resch, Lucie Dixsaut, Victoire Gorden, Liliane Glauser, Johannes Gräff

Surprisingly little is known about how remote fearful memories are stored and attenuated. Khalaf et al. used independent fear memory attenuation paradigms, engram-based tagging techniques, and chemogenetic tools to alter neuronal activity (see the Perspective by Frankland and Josselyn). They found that a discrete subset of neurons within an ensemble is engaged during recall after memory attenuation, which correlated with fear reduction. Memory updating and extinction mechanisms thus likely coexist to make this happen. These findings support the notion that effective memory attenuation is mediated by a rewriting of the original memory trace of fear toward one of safety.

Reactivation of Recall-Induced Neurons in the Infralimbic Cortex and the Basolateral Amygdala After Remote Fear Memory Attenuation

Ossama Khalaf, Johannes Gräff

Here, we show—by cellular compartment analysis of temporal activity using fluorescence in situ hybridization—that such reactivation also occurs in the basolateral amygdala and the infralimbic cortex, two brain areas known to be involved in fear memory attenuation. These results provide further experimental support for effective traumatic memory attenuation likely being mediated by an updating of the original fear trace towards safety.

fnmol-12-00070-g001.jpg
Review_Fig..png

Structural, Synaptic, and Epigenetic Dynamics of Enduring Memories

Ossama Khalaf, Johannes Gräff

The H50Q Mutation Enhances α-Synuclein Aggregation, Secretion, and Toxicity

Ossama Khalaf, Bruno Fauvet, Abid Oueslati,..., Hilal Lashuel

Over the last two decades, the identification of missense mutations in the α-synuclein (α-Syn) gene SNCA in families with inherited Parkinson disease (PD) has reinforced the central role of α-Syn in PD pathogenesis. Recently, a new missense mutation (H50Q) in α-Syn was described in patients with a familial form of PD and dementia. Here we investigated the effects of this novel mutation on the biophysical properties of α-Syn and the consequences for its cellular function.

H50Q.png

Ca2+–Calmodulin regulates SNARE assembly and spontaneous neurotransmitter release via v-ATPase subunit V0a1

Dong Wang, Daniel Epstein, Ossama Khalaf, ..., P. Robin Hiesinger

Most chemical neurotransmission occurs through Ca2+-dependent evoked or spontaneous vesicle exocytosis. In both cases, Ca2+ sensing is thought to occur shortly before exocytosis. In this paper, we provide evidence that the Ca2+ dependence of spontaneous vesicle release may partly result from an earlier requirement of Ca2+ for the assembly of soluble N-ethylmaleimide–sensitive fusion attachment protein receptor (SNARE) complexes. We show that the neuronal vacuolar-type H+-adenosine triphosphatase V0 subunit a1 (V100) can regulate the formation of SNARE complexes in a Ca2+–Calmodulin (CaM)-dependent manner. Ca2+–CaM regulation of V100 is not required for vesicle acidification. Specific disruption of the Ca2+-dependent regulation of V100 by CaM led to a >90% loss of spontaneous release but only had a mild effect on evoked release at Drosophila melanogaster embryo neuromuscular junctions. Our data suggest that Ca2+–CaM regulation of V100 may control SNARE complex assembly for a subset of synaptic vesicles that sustain spontaneous release.

JCB_edited.jpg

Our memories are the records of the experiences we gain in our everyday life. Over time, they slowly transform from an initially unstable state into a long-lasting form. Many studies have been investigating from different aspects how a memory could persist for sometimes up to decades. In this review, we highlight three of the greatly addressed mechanisms that play a central role for a given memory to endure: the allocation of the memory to a given neuronal population and what brain areas are recruited for its storage; the structural changes that underlie memory persistence; and finally the epigenetic control of gene expression that might regulate and support memory perseverance. Examining such key properties of a memory is essential towards a finer understanding of its capacity to last.