Welcome to the Paradis Lab
Suzanne Paradis, Ph.D.
Department of Biology
415 South St.
Waltham MA 02454
E-mail | Faculty Profile | CV | Pubmed
Research in our laboratory seeks to bridge the gap between molecular and systems neuroscience by defining the genes that instruct neurons to establish and modify their synaptic connections and dendritic morphology. Neurons convey information by making synaptic connections onto other neurons, and receive information via synaptic inputs onto their dendritic arbor. Each type of neuron in the mammalian CNS has a distinctive dendritic arbor that is typically extensively branched, and this arbor influences the specific function of the neuron in part by instructing which synaptic connections it receives.
Another key aspect of neuronal circuit formation is achieving the proper balance of excitation and inhibition within the circuit. It is thought that this balance is required for normal cognitive development and function; disruptions to this balance can have pathological consequences for circuit function as demonstrated by the manifestation of devastating neurological impairments, including epilepsy (McNamara et al., 2006) and Autism Spectrum Disorders (ASD) (Fernandez and Garner, 2007; Rubenstein and Merzenich, 2003). There are two important obstacles to understanding the basic mechanisms underlying these types of developmental disorders: a lack of knowledge about which genes mediate experience-dependent construction of brain circuits, and a lack of ability to directly observe the influence of genes and experience on brain circuits in the living animal.Our research program aims to identify the function and examine the influence of genes and sensory experience on the development of neuronal circuits in living vertebrate animals. We pioneered an unbiased, forward genetic, RNAi-based screen in cultured primary neurons that revealed new genes which function to regulate synapse formation and dendritic morphology (Ghiretti and Paradis, 2011; Paradis et al., 2007).
Using this technique, our research uncovered a novel signaling mechanism that rapidly (within minutes) drives GABAergic synapse formation (Kuzirian et al., 2013). We also discovered that sensory experience concurrently activates signaling pathways that both promote and inhibit dendritic complexity (Ghiretti et al., 2014). Our work suggests that a key feature of structural plasticity is a balance of these opposing signals.
We are currently using gene knockdown and gene targeting approaches both in vitro and in vivo to elucidate the molecular mechanisms by which genes of interest regulate synapse and dendrite development. In addition, in collaboration with the lab of Dr. Steve Van Hooser at Brandeis (https://sites.google.com/site/vanhooserlab/), we utilize 2-photon in vivo imaging to examine the function of specific genes in regulating activity-dependent changes in neuronal morphology in an intact cortical circuit.
Back row, L-right: Suzanne Paradis, Amy Ghiretti, Marissa Kuzirian, Anna Moore, Katelyn Kenny, Jackie McDermott, Danielle DiTirro
Front row, L-right: Daniel Acker, Aram Raissi, Deborah Rothbard, Mugdha Deshpande