Synaptic function

Throughout development, the brain dynamically regulates the composition of its extracellular fluid compartments. Proteins secreted into these compartments, defined collectively as the brain secretome, have been shown to influence key neurodevelopmental processes from cell migration to synaptogenesis. Nonetheless, only a fraction of the brain secretome has been comprehensively characterized, leaving the developmental contribution of many disorder-associated secreted proteins unexplored. A growing body of literature highlights the dysregulation of extracellular fluids in the brain as a common fe

Transcranial focused ultrasound (tFUS) targets deep brain areas by non-invasively administering low intensity ultrasound through the brain with a high spatial resolution (Zhang et al., 2021). Previous results indicate that stimulating neural cells at specific pulsing frequencies is neuroprotective (Manippa et al., 2022). We were therefore interested in determining whether a similar approach could be taken with focused ultrasound stimulation. To this end, we prepared acute rat hippocampal slices and exposed them to 40Hz pulsing ultrasound for 1hr. Following a proteomics screen, we noted an incr

Dementia with Lewy Bodies (DLB) is the second most common neurocognitive pathology characterized by pathogenic deposition of α-synuclein-laden Lewy bodies within vulnerable neurons, including those of the hippocampus (HC). The strongest risk factor for sporadic Alzheimer’s disease (AD), and recently demonstrated for DLB, is the ε4 allele of apolipoprotein (APOE4) that is a major lipoprotein in the central nervous system playing a leading role in maintaining lipid homeostasis. Our group recently demonstrated that the APOE4 aggravates cognitive deficits in a mouse model of prodromal DLB – corrob

…vital role in governing RNA's fate and function. N6-methyladenosine (m6A) is the most abundant and functionally relevant RNA modification, affecting mRNA splicing, transport, storage, stability, translation, and decay. The Fat Mass and Obesity-related protein (FTO) is an m6A eraser that plays a role in memory formation in the brain. Our study aimed to investigate FTO's role in neurons and the modulation of its expression. We found that FTO is widely expressed in the mouse brain and increases d

…integrating, and responding to synaptic transmission. Astrocytes were shown to sense glutamate, the most abundant excitatory neurotransmitter in the brain, which occurs by acti

…of XPO7 in neuronal development and function, XPO7 knock-down (KD) was induced in

Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting 1% of over 65's; there is currently no effective treatment. Dopaminergic neuronal loss is hallmark in PD and yet despite decades of intensive research there is still no known therapeutic which will completely halt the disorder. As a result, identification of interventive therapies to reverse or prevent PD are essential. Using genetically faithful models (induced pluripotent stem cells and knock-in mice) of familial late onset PD (LRRK2 G2019S and GBA N370S) we have contributed to the literature that neur

Microglia are implicated in a variety of functions in the central nervous system, ranging from shaping neural circuits during early brain development, to surveying the brain parenchyma, and providing trophic support to neurons across the entire lifespan. In neurodegeneration, microglia have been considered for long time mere bystanders, accompanying and worsening neuronal damage. However, recent evidence indicates that microglia can causally contribute to neurodegenerative diseases, and that their dysfunction can even be at the origin of the pathology. In fact, the broad range of physiological

…and store that information amongst the synaptic connections between the neurons that both comprise the network and govern its function. The strength and organization of synaptic connections adjust during learning, but many cognitive neural systems are multifunctional, making it unclear how continuous activity alternates between the transient and discrete cognitive functions like encoding current information and recollecting past information, without changing the connections amongst the

…and store that information amongst the synaptic connections between the neurons that both comprise the network and govern its function. The strength and organization of synaptic connections adjust during learning, but many cognitive neural systems are multifunctional, making it unclear how continuous activity alternates between the transient and discrete cognitive functions like encoding current information and recollecting past information, without changing the connections amongst the

Christophe Mulle is a cellular neurobiologist with expertise in electrophysiology of synaptic transmission and an international leader in studies on glutamate receptors and hippocampal synaptic plasticity. He was among the first to identify and characterize functional nicotinic receptors in the mammalian brain while working in the laboratory of Jean-Pierre Changeux at the Pasteur Institute. He then generated knock-out mice for KAR subunits at the Salk Institute in the laboratory of Steve Heinemann, which have proven to be instrumental for understanding the function of these elusive glutamate r