Neurotransmission

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by reduction or absence of neurofibromin due to mutations in the NF1 gene that result in multiple behavioral defects among other aberrant phenotypes. To directly assess the consequences of Nf1 deficiency on evoked neuronal activity, potentially underlying neuroplasticity defects, we utilized null mutations, point mutations, and RNA interference to manipulate Nf1 levels in Drosophila melanogaster. Our study focused on assessing the functional alterations in the giant fiber system, a well-established electrophysiological model to study

…treatment with antiepileptic drugs on neurotransmission and functional properties of layer 2/3 pyramidal cells in th

PKA, influenced by retrograde signalling from muscle contraction, enhances neurotransmission at the neuromuscular junction (NMJ). This occurs through the phosphorylation of key molecules in synaptic vesicle exocytosis, SNAP-25 and Synapsin-1. The BDNF/TrkB pathway, augmented by muscle contraction, is a known regulator of retrograde control in ACh exocytosis at the NMJ. This modulation, including muscarinic receptors M1 and M2 (mAChRs) linked with both PKA and BDNF/TrkB signalling, has not been studied until now. Here, we investigate how synaptic activity and muscle contraction regulate PKA sub

The endoplasmic reticulum (ER) is a network of membranes that regulates different cellular processes such as protein and lipid biogenesis, Ca2+ homeostasis and transport. Within neurons, the ER surface is huge and forms distinct structures depending on its cellular localization. Dense stacks of ER membranes, known as cisterna, have been identified in neurons, notably within the axonal initial segment (AIS, cisternal organelle) and dendritic spines (spine apparatus). While the specific functions of these cisternal structures are not fully understood, their role in spines is associated with calc

Genomic medicine provides potential for novel diagnostic targets and therapeutic solutions. As mutations in human genes are identified and associated with neurodevelopmental disorders, the need to create personalized treatment protocol has increased. We have previously reported the first mutation in type 2 vesicular monoamine transporter (VMAT2), causing an infantile Parkinsonism phenotype Parkinsonism-dystonia-2 (PKDYS2) (OMIM 618049)( Rilstone et al., NEJM, 2013). Over the past decade, several additional mutations have been identified in VMAT2, giving rise to a broad phenotype spectrum and v

…and established-epilepsy, such as neurotransmission, synaptic homeostasis, inflammation, blood-brain

The advent of next generation sequencing ushered in a ten-year period of exuberant technology development, enabling the quantification of gene expression and epigenetic features within individual cells, and within intact tissue sections. In this seminar, I will outline our technological contributions, beginning with the development of Drop-seq, a method for high-throughput single cell analysis, followed by the development of Slide-seq, a technique for measuring genome-wide expression at 10 micron spatial resolution. Using a combination of these techniques, we recently constructed a compreh

John DowlingJohn E. Dowling received his AB and PhD from Harvard University. He taught in the Biology Department at Harvard from 1961 to 1964, first as an Instructor, then as assistant professor. In 1964 he moved to Johns Hopkins University, where he held an appointment as associate professor of Ophthalmology and Biophysics. He returned to Harvard as professor of Biology in 1971, was the Maria Moors Cabot Professor of Natural Sciences from 1971-2001, Harvard College professor from 1999-2004 and is presently the Gordon and Llura Gund Professor of Neurosciences. Dowling was chairman of the Biolo

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

…has shown that the dlPFC has unique neurotransmission and neuromodulation compared to the classic actions found in the primary visual cortex, including mechanisms to rapidly weaken PFC connections during uncontrollable stress. Reduced regulation of these st