CUNY School of Medicine






Left: Expression of glt-3 in the canal cell    Right: Expression of glt-1 around the nerve ring
PostDoc Position in the Mano Lab, City College, New York City:

Novel strategies for glutamate clearance in a glia- deprived synaptic hub: Lessons from C. elegans

We study normal and pathological signaling by the neurotransmitter glutamate. The job opening is to study the physiology of functional neuronal circiut isolation and glutamate transporters. In addition to standard C. elegans methods (such as genetics, cell and molecular biology) we will study transporter function using electrophysiology in Xenopus oocytes expressing nematode cRNA, and by imaging neuronal activity in intact worms using Ca2+-sensitive GFP and microfluidic chips.


Our lab is at the department of Physiology, Pharmacology, & Neuroscience, the CUNY School of Medicine at City College, the City University of New York (CUNY). Our campus is growing, with the recent addition of two new science buildings: the Advanced Science Research Center (ASRC, a facility that hosts top research groups from the CUNY system and includes a new Neuroscience center), and the City College Neuroscience Cluster at the new Center for Discovery & Innovation (CDI) building (where our lab is located). City College is located in western Harlem in uptown Manhattan, in close proximity to many leading academic institutes, placing us at the heart of an exciting and collaborative academic atmosphere, a hub of neuroscience research, and vibrant city life. Good housing options are available close to campus, and we are in commuting distance from suburban areas in NY, NJ, and CT.


If you are a motivated, multitasking neurophysiologist interested in exploring new approaches in molecular neuroscience and genetics, this project will be an excellent fit for you. Applicant should have a PhD in a relevant field of biology and a record of excellence in neurophysiology. Please e-mail a brief cover letter describing your research experience, CV, and contact information for 2-3 references to:

Project Abstract

Novel strategies for glutamate clearance in a glia- deprived synaptic hub: Lessons from C. elegans

The widespread use of Glutamate (Glu) as the major excitatory neurotransmitter (NT) in the mammalian brain is both critical for normal physiology and a source of predicaments: a) As seen in stroke and a range of neurodegenerative diseases, any disruption in Glu clearance causes its accumulation, leading to over- excitation of postsynaptic cells and excitotoxic neurodegeneration. b) The use of the same NT in so many adjacent synapses can cause signaling to “bleed over” between neuronal circuits, and the loss of processing fidelity. An idealized view of the brain describes synapses as well insulated from each other, enveloped by glia that expresses high levels of Glu clearing transporters (GluTs). However, a more realistic examination reveals that some particularly-important brain areas (e.g., hippocampus) show severely deficient glial isolation, with estimated 2/3 of released Glu seeping out of the original synapse. How sufficient Glu clearance is achieved in glia-deficient brain areas remains unclear. To overcome the limitation of current techniques we will study Glu clearance in the glia-deficient synaptic hub of the C. elegans nerve ring. We are aided by the availability of information on the precise identification of individual neurons, the exact location of their synapses, the circuits that they participate in, and the sensory inputs and behavioral outputs of these circuits. Together with animal transparency and the wide availability of optogenetic tools, this is an ideal system to study Glu clearance without perturbing interstitial fluids. In our recent studies we have discovered that specific synapses fall into watershed territories of Glu clearance, and that synapses might be affected by the agitation of body fluids. We therefore propose a novel concept, where Glu clearance in a glia-deficient synaptic hub can be robust enough to allow functional synaptic isolation. Such robust clearance depends on division of labor between proximal and distal GluTs, and is facilitated by agitation and perfusion of interstitial fluids. To provide further support to this model we will use genetically-encoded florescent Ca2+ reporters (GCaMP) to follow synaptic activity and assign additional synapses and circuits to GluT drainage territories; we will stimulate one circuit and record responses from an adjacent one to detect spillover; we will use genetically-encoded fluorescent detectors to study the flow of Glu in the interstitial space; we will study the effect of paralysis on neuronal responses and Glu flow; We will correlated the differences between the structure of proximal and distal GluTs to potential differences transport in affinity and capacity. These studies will provide novel insights to mechanisms of robust Glu clearance in the absence of glia, and highlight the significance of agitation of interstitial fluids in synaptic areas that are deficient in glia insulation, a feature shared between nematodes and some areas of the mammalian brain. These insights will aid in the design of future therapeutic interventions to prevent excitotoxicity (seen in stroke and a range of neurodegenerative diseases), and highlight the significance of vascular pulsatility in CNS physiology. 

Supported by NIH grant # 1R21NS098350-01



Physiol. Pharm. & Neurosci, City College, C. elegans@CUNY



The Mano Lab

Department of Physiology, Pharmacology, & Neuroscience

Sophie Davis Biomedical School, City College, The City University of New York.