Research

How do memories form? How do humans learn? These processes all involve plastic changes in neural circuits. The changes occur mostly at synapses – specialized points of contact between neurons. The Maricq lab is working towards a mechanistic understanding of synaptic development, function and plasticity. Much of the molecular machinery that is required for synaptic development and synaptic plasticity has not been identified. To learn more about how synapses work, we study the development and function of simple neural circuits in the nematode Caenorhabditis elegans. Our strategy begins with genetics. We first identify genes required for circuit function. We then continue with a multidisciplinary approach aimed at characterizing the function of the identified gene products.

C. elegans displaying light-activated control of motor activity

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The Maricq lab conducts research in three general areas: 

I. Analysis of synaptic signaling, network activity and behavior

Glutamate is the major excitatory neurotransmitter in the brain and exerts its actions by binding to several classes of glutamate-activated receptors. Since dysfunction of glutamate-receptor-mediated signaling is implicated in various mental health and neurological disorders, there is intense interest in gaining a greater understanding of the molecules required for the assembly, localization and function of ionotropic glutamate receptors (iGluRs). Our research has demonstrated that iGluRs function in the context of a signaling complex, which contains the auxiliary proteins SOL-1, STG-1 and STG-2. We have also discovered a specific toxin that enhances the activity of iGluRs. These new discoveries will help provide a mechanistic understanding of how different classes of iGluRs are distributed to and maintained at specific synapses, how they participate in synaptic communication, and how they contribute to the behavior of C. elegans.

II. Analysis of neuromuscular development and function in C. elegans

Nicotinic (cholinergic) neurotransmission plays a critical role in the vertebrate nervous system and underlies nicotine addiction, and nicotinic receptor dysfunction leads to neurological disorders. The C. elegans neuromuscular junction (NMJ) shares many characteristics with neuronal synapses, including multiple classes of post-synaptic currents.  We have identified two genes required for the major excitatory current found at the C. elegans NMJ: acr-16, which encodes a nicotinic AChR subunit homologous to the vertebrate a7 subunit, and cam-1, which encodes a Ror receptor tyrosine kinase. Future studies will focus on identifying the molecular machinery that is required for the development and function of the neuromuscular junction.

III. Studies of rhythmic behavior and Ca2+ oscillations in C. elegans

Rhythmic activities are ubiquitous biological phenomena and can be observed in cells, tissues and the behavior of most organisms. For example, heart and respiratory rate, intestinal peristalsis, circadian activity, and ovulation are all rhythmic behaviors and reflect the underlying activities of a diverse array of regulatory pathways. We have found that the C. elegans Rho/Rac family guanine nucleotide exchange factor, VAV-1, has a crucial role in three rhythmic behaviors. TheVAV-1 signaling pathway appears to controls rhythmic behaviors by dynamically regulating the concentration of intracellular Ca2+. Future studies will focus on identifying other gene products that contribute to the VAV signaling pathway, and the regulation and generation of rhythmic behaviors.