Laboratory of Molecular Neurobiology
Welcome to the Laboratory of Molecular Neurobiology at the Boston University School of Medicine. Under the direction of David H. Farb, PhD, the laboratory is involved in basic research on neurotransmitter receptor pharmacology, the mechanisms by which receptors are regulated and how activation of these receptors translates into modulation of neural network activity in vivo. The laboratory uses in vitro and in vivo techniques to investigate drug targets. Activities can broadly be divided into the following areas:
The Dancing Place Cells
Double click the image to see Place Cells Dance
The laboratory uses in vitro and in vivo electrophysiological techniques to investigate how drugs modulate neuronal activity. The Dancing Place Cells above were created from in vivo recordings of actual hippocampal neurons in the brains of freely behaving rodents. The Laboratory is working to identify changes in hippocampal function that underlie cognitive deficits associated with aging and disease and, to assess for the functional neural network correlates associated with effective therapeutics.
In vivo electrophysiological studies are conducted in freely behaving animal models using indwelling micro-electrode arrays to record drug-induced changes in neural network activity during performance of relevant behavioral tasks of learning and memory function. The laboratory has three temperature controlled recording rooms, each with its own Plexon MAP system dedicated to this exciting research. The Laboratory of Molecular Neurobiology is part of the Boston University Center for Systems Neuroscience. Our research in this area is funded in part by the National Institute on Aging.
In vitro electrophysiological research is carried out in dedicated workrooms. Whole-cell patch clamp and two-electrode voltage clamp techniques are presently being used to study the modulation of GABA and glutamate receptors in both cultured neurons and in Xenopus oocytes that have been injected with mRNA coding for neurotransmitter receptors. A high-throughput electrophysiology (HTEP) station, developed in our laboratory, is used for rapid screening of chemical libraries.
Studies of drug-induced changes in post synaptic potentials and long-term potentiation are carried out using electrophysiological techniques in brain slice preparations.
In addition to the various in vitro and in vivo electrophysiology approaches described above, the laboratory also uses molecular biological techniques to study neurotransmitter receptors implicated in disease state dependent responses to drugs. Regulation of the subunit composition, and hence pharmacological specificity, of the receptors under investigation can take place at the genomic level. Examination of the promoter and coding sequences yields valuable information that complements the other approaches used in the laboratory.
Drug delivery via nanoparticles encapsulating hydrophilic or hydrophobic molecules are being engineered for delivery across the blood brain barrier. Nanoparticle composition is being tailored to better deliver drug to specific target sites. Neuroactive drugs and proteins, biomarkers for novel diagnostics, sensitive dyes for neural mapping, and many other applications are envisioned. The major advantage of this technique is the noninvasive delivery of molecules to the CNS via a peripheral injection.
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