Barry A. Trimmer, Ph.D.
Professor
Depts. Biology, Pharmacology and Neuroscience
Tufts University
Dana Hall
Medford, MA 02155
Phone: 617-627-3924
Email: Barry.Trimmer@Tufts.edu
Please visit the Trimmer Lab Page

Research interests

My laboratory is interested in the neural processes that organize sensory and motor information particularly the way that receptors and transmitters coordinate electrical and chemical signals. We use an insect (the tobacco hornworm, Manduca sexta) as our model system because it has a brain with fewer neurons, many of which can be identified and kept alive outside the animal. Currently we are pursuing three major projects:

The range and specificity of nitric oxide signaling in the brain

Some neurons signal by producing an unstable soluble gas named nitric oxide (NO). This unusual messenger was discovered only recently and comparatively little is known about its role in the brain. We have identified individual NO-producing and responding neurons in the living nervous system and our goal is to establish how they communicate.

The structure and function of neuronal acetylcholine receptors

Nicotinic acetylcholine receptors. The nAChRs mediate very fast electrical responses but can also generate large and comparatively long-lasting changes in intracellular calcium. We are studying the function of this calcium signal in populations of neurons in culture and in specific neurons that control reflex movements. At least one of the actions of nAChR stimulation is to activate nitric oxide synthase and produce cGMP in a subset of abdominal neurons.

An additional goal is to understand how information from these receptors is used during normal behavior. We have used injections of double stranded RNA (RNAi) block the production of individual gene products (such as subunits of the nAChR) and plan to use this to "knock out" specific receptors in fully grown animals. The behavior of these animals can then be analyzed (see soft-bodied locomotion link) and compared to animals with the normal compliment of gene products.

Muscarinic acetylcholine receptors. In addition to rapid synaptic signaling ACh also elicits slower, long-lasting effects via muscarinic acetylcholine receptors (mAChRs). In Manduca, one of these effects is to increase the excitability of a specific motoneuron (PPR) so that it fires action potentials in response to inputs that were previously ineffective. This change outlasts the sensory stimulation and therefore modulates subsequent behavior. The biochemical changes evoked by Manduca mAChRs include an increased turnover of signaling phospholipids in the membrane (PIP2), the mobilization of calcium, and an increase in the production of cGMP.

Significance of these studies. Many of these research findings have biomedical significance: in particular, Manduca's nicotine-resistance is of interest commercially (in developing pesticides), ecologically (in insect-plant interactions), and medically (in treating nicotine addiction). Changes in neuronal biochemistry and excitability such as those mediated by mAChRs are likely to be critical in the etiology of epilepsy and in alterations in behavior caused by drugs or experience. By focusing on identified neurons with known functions, we are hopeful that our research will help identify the mechanisms and define the roles of particular receptors in the central nervous system.

The neural control of soft-bodied locomotion

Unlike animals with hard skeletons, caterpillars do not have joints to restrict movements. They can crumple, compress and rotate body parts with virtually unlimited freedom. We are trying to understand how the nervous system controls these complex movements. These studies have potential applications in the design and control of a new type of flexible robot. Such robots could be used to navigate through pipelines or intricate structures such as blood vessels and air tubes.

Selected Recent Publications

Vermehren, A., and Trimmer, B.A. (2005) The expression and function of two nicotinic subunits in insect neurons. J. Neurobiol. 62, 289-298.

Metzoff, S., Papastathis, N., Takesian, A. and Trimmer, B.A. (2004) The biomechanical and neural control of hydrostatic limb movements in Manduca sexta. J. Exp. Biol. 207, 3043-53.

Qazi, S., Beltukov, A. and Trimmer, B.A. (2004) Simulation modeling of ligand receptor interactions at non-equilibrium conditions: Processing of noisy inputs by ionotropic receptors. Math. Biosciences. 187. 93-110.

Trimmer, B.A., Aprille, J. R., Modica Napolitano, J.S. (2004) Nitric oxide signalling: Insect brains and photocytes Biochemical Society Annual Symposium vol. 71. Free Radicals: Enzymology, Signalling and Disease. Portland Press, London. ISBN 1855781611

Fickbohm, D. and Trimmer, B.A. (2003) Antisense inhibition of neuronal nicotinic receptors in the tobacco-feeding insect, Manduca sexta. Arch Insect Biochem Physiol, 53: 172-85.

Issberner, J.I. Shauer, C. Trimmer, B.A and. Walt, D (2002) Combined imaging and chemical sensing of L-glutamate release from the foregut plexus of the Lepidopteran, Manduca sexta J. Neurosc. Methods. 120, 1-10

Zayas, R.M. Qazi, S. Morton, D.B. and Trimmer, B.A. (2002) Nicotinic-acetylcholine receptors are functionally coupled to the NO/cGMP- pathway in insect neurons. J. Neurochemistry. 83:421-431.

Vermehren, A., Qazi, S. and Trimmer, B. A (2001) The nicotinic a subunit MARA1 is necessary for cholinergic evoked calcium transients in Manduca neurons. Neuroscience Letters 313, 113-116.

Trimmer, B. A., Aprille, J. R., Dudzinski, D.M., Lagace, C.J., Lewis, S.M., Michel, T., Qazi, S., Zayas, R.M.(2001). Nitric oxide and the control of firefly flashing. Science Volume 292, 2486-2488.

Belanger, J. H., Bender, K., J. and Trimmer, B. A. (2000). Context-dependency of a limb-withdrawal reflex in the caterpillar Manduca sexta. J. Comp. Physiol. A. 186, 1041-1048