{"id":2672,"date":"2010-11-04T12:05:51","date_gmt":"2010-11-04T16:05:51","guid":{"rendered":"https:\/\/www.bumc.bu.edu\/ppb\/?page_id=2672"},"modified":"2025-11-18T13:59:37","modified_gmt":"2025-11-18T18:59:37","slug":"lmn","status":"publish","type":"page","link":"https:\/\/www.bumc.bu.edu\/ppb\/education\/pharmacology\/training-program\/laboratories\/lmn\/","title":{"rendered":"Laboratory of Molecular Neurobiology"},"content":{"rendered":"\n\n\n
\"Electrophysiological<\/p>\n

Welcome to the Laboratory of Molecular Neurobiology<\/em> at the Boston University School of Medicine. The members of the laboratory are working together as a team under the direction of David H. Farb, PhD<\/a>, to elucidate the mechanisms by which receptors are regulated, how activation of these receptors modulates neural network activity in vivo<\/i> and, how this in turn\u00a0contributes to the onset and progression of memory deficits in age-related neurodegenerative diseases.\u00a0The laboratory uses a systems neuroscience approach to understanding the functional interactions within neural networks implicated in neurological and psychiatric diseases. Drs. David Farb and Marcia Ratner<\/a> of the Laboratory of Molecular Neurobiology were one of the first teams of investigators to successfully use in vivo<\/em> electrophysiological techniques\u00a0to advance our understanding of how systemically administered drugs\u00a0modulate neural\u00a0network\u00a0activities implicated in memory\u00a0deficits associated with\u00a0age-related amnestic mild cognitive impairment (Hippocampus,<\/span>\u00a02015<\/a>), Alzheimer’s disease (AD) (Heliyon, 2021<\/a>) and age-related hypertension (Geoscience 2025<\/a>). <\/span>The Laboratory was the first to identify baseline ripple band hyperactivity as measured by increased average peak ripple amplitude (a core component of local field potential power in the ripple band) during periods of quiet wakefulness in the TgF344-AD rat model of AD (see panels F and G from our 2021 Heliyon paper). \u00a0The Laboratory was also the first to demonstrate that activity in this high frequency band which, is implicated in memory function in animals and humans, does not increase further when the neural circuitry is challenged with an investigational therapeutic (i.e., \u03b15IA) designed to improve memory by decreasing tonic inhibition mediated by \u03b15 subunit containing GABA-A receptors which are highly expressed in the hippocampus. \u00a0Drs. Farb and Ratner<\/a> are also collaborating to\u00a0advance the use of in vivo<\/em> electrophysiology as an applied science in preclinical neurotoxicology<\/a> research (<\/span>Frontiers in Toxicology, 2022<\/a>). \u00a0<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n\n
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Silicon Probe Microelectrodes<\/h2>\n

The\u00a0Laboratory is currently using ultra fine silicon microelectrode arrays<\/em>\u00a0(see figures and video below) to identify subregion specific changes in local field potentials and single unit activity that underlie cognitive deficits associated with aging and disease and, to assess for the functional neural network correlates associated with effective therapeutics for Alzheimer’s disease. \u00a0Due to their unique design and flexible electrode layouts, silicon microelectrode\u00a0arrays\u00a0permit for recording across strata within a hippocampal subregion and, from more than one subregion (e.g. dentate gyrus, CA3 and CA1). Long single shank silicon probes such as the one pictured below permit recording from multiple hippocampal subregions with different current sources and sinks.<\/p>\n

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The figures below demonstrate how local field potentials <\/strong>are<\/em>\u00a0recorded and visualized for analysis. Single unit activity associated with high frequency (140 to 200 Hz) sharp wave ripples in the CA1 hippocampal subregion are shown inside box in lower figure. \u00a0Real-time recordings of ripples with associate action potential “spikes” are shown in the video below titled “Recording of Ripples and Action Potential Spikes in Real-Tim<\/em>e<\/strong>“. \u00a0The data shown in this video were acquired using a 4 shank 32 electrode silicon microlectrode array while the animal was awake and immobile in a familiar environment as reported in our paper published in Cell Press Heliyon, 2021<\/a>. This\u00a0research is funded in part by the National Institute on Aging. \u00a0The Laboratory of Molecular Neurobiology is part of the\u00a0Boston University Center for Systems Neuroscience<\/a>.<\/p>\n

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Sharp Wave Ripple with Associated Multiple Unit Activity<\/h3>\n

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Silicon Probe Microelectrode Arrays<\/h3>\n
\n\/ppb\/files\/2020\/01\/SiliconProbesforweb.mp4<\/a><\/video><\/div>\n

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Recording of Ripples and Action Potential Spikes in Real-Time<\/h3>\n
\/ppb\/files\/2021\/12\/Ripples-for-lab-website.mp4<\/a><\/video><\/div>\n\n\n\n
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Place Cells<\/h2>\n

In vivo<\/em> electrophysiological recordings have been used to study neuronal activity and hippocampal dependent learning and memory function since the Nobel Prize winning discovery of “Place Cells<\/strong>” by O’Keefe\u00a0and Dostrovsky in 1971<\/a>. \u00a0Place cells, are hippocampal pyramidal cells that fire with a greater frequency when an animal is in a specific location. \u00a0This activity pattern can be visualized in the video below of the Dancing Place Cells<\/strong><\/em>\u00a0which was made from actual data recordings of hippocampal place cells.<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

The Dancing Place Cells Video<\/h3>\n
\/ppb\/files\/2020\/01\/thedancingplacecellsforweb.mp4<\/a><\/video><\/div>\n\n\n\n
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Place Fields<\/h2>\n

Place cells establish stable “place fields<\/strong><\/em>” within a given environment and change their firing patterns (“remap”) when the animal is moved to a novel location in a classic remapping paradigm such as that shown in the remapping video below.<\/p>\n

The place fields of a rat “remapping<\/strong>” when the animal is moved from a familiar square environment to a novel cylindrical one is shown in the\u00a0figure below. \u00a0The activity of these place cells is altered by aging and diseases. \u00a0Place cell activity can also be modulated with drugs (e.g., cognitive enhancers). \u00a0In recent years, advances\u00a0in vivo<\/em>\u00a0electrophysiology coupled with increased understanding of place cell firing dynamics has opened the door to the use of this technology as a research tool in the preclinical drug discovery process.\u00a0Pyramidal cells with defined place fields in at least one environment are subsequently analyzed for drug-induced effects on firing rates, spatial correlations across environments, and spatial information content per spike.<\/p>\n

Place Fields<\/h3>\n

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Remapping Paradigm<\/h3>\n