Regents Professor

Arizona Research Laboratories Division of Neurobiology

Ph.D. 1968, University College, London

Four areas of research are being pursued in my laboratory. We also administer, with international collaborators in Japan and Germany, the NSF-supported Drosophila nervous system database FLYBRAIN (http://www.flybrain.org/)

Higher brain centers for learning and memory. The brains of insects are equipped with paired mushroom bodies– centers that, like the hippocampus, play a role in spatial learning and memory and in context-dependent sensory integration. We are studying the organization of mushroom bodies in the cockroach, Periplaneta americana, recording from identified neurons during multisensory stimulation. We are also investigating neuronal modification using paired stimuli that condition motor actions. Mushroom bodies are being investigated anatomically, with particular attention to ensembles of peptidergic neurons that subdivide the honey bee mushroom bodies into discrete parallel microprocessors that may play crucial roles in sensory association. Comparisons between mushroom body organization in advanced and primitive Hymenoptera suggest interesting parallels with the evolutionary elaboration of the vertebrate forebrain.

Comparative studies amongst taxa reveal common principles of organization. Information derived from one species can be confidently integrated with information derived from another. For example, although it is not feasible to obtain long-term intracellular recordings from neurons in Drosophila mushroom bodies, there are obvious similarities between their cellular arrangements and those in cockroaches.

Development of learning and memory neuropils. Regions of the brain specialized for learning and memory comprise intricate yet modifiable neural circuits. Studying how such circuits develop will provide insights into how neurons are arranged to provide substrates for sensory association and subsequent modifications of efferent neuron responses. Although not yet manipulatable using gene technology, the cockroach has certain advantages over Drosophila. It is an evolutionary basal taxon with many primitive features. Cockroaches develop through many instars (hemimetaboly), each being differently challenged by the sensory environment. The following are a few of the many questions that can be asked of this system. How does the internal network of the mushroom bodies develop, and which connections are necessary and sufficient for learning to occur? What roles do hormones play in the proliferation and differentiation of the many hundreds of thousands of intrinsic neurons in the mushroom bodies? To what sensory combinations are mushroom body output neurons tuned at different developmental stages, and are differences of stimulus selectivity associated with specific age-related alterations of intrinsic neuron circuits?

Brain evolution. Brain organization is remarkably consistent among closely related taxa. For example, the brains of lepidopterous insects share numerous structural similarities, but are distinct from the brains of coleopterans. Because neural architectures are so conserved, they can serve as diagnostics for deriving possible phylogenetic relationships amongst the invertebrates. Defined structural features (characters) of brain architectures are scored as present or absent in representatives across the two protostome clades– the ecdysozoans and lophotrochozoans– thereby determining relatedness among taxa. Phylogenies derived from cladistic analysis demonstrate that archaeognathan insects (which are primitive) are more closely related to primitive crustaceans (branchiopods) than to myriapods (e.g. centipedes). This supports results from other laboratories using molecular techniques to derive phylogenies.

Such comparisons are invaluable for investigating the significance of neuronal arrangements. For example, in the fly visual system, a specialized achromatic neuropil called the lobula plate contains systems of wide-field neurons that collate information about visual flow fields over the retina. These neurons supply pathways involved in visual balance. An agile and highly visual isopod species (a crustacean) also has a lobula plate equipped with wide-field neurons. Because isopods are separated from flies by at least 400 million years, it would appear that these similar centers have evolved independently. We are presently investigating whether the two lobula plates have identical neural arrangements, transmitter substances, and connections. Related to this work is an ongoing study on ancient arthropods of the Burgess Shale fauna, certain of which show well-preserved compound eyes and traces of optic lobes and brain.

Functional organization in visual systems. Research on the organization of the insect visual system focuses on the functional dissection of neural circuits that compute directional motion, and the organization of neurons that are tuned to small-field orientation and hence form discrimination. Research employs intracellular recording from extremely small retinotopic neurons that respond to motion and direction cues with non-spiking (graded) potentials. Immunocytology and cell marking are used to elucidate the distribution of transmitter substances in the system with the aim of determining what transmitters are used by identified neurons and how these are interconnected. We are collaborating with Professor Charles Higgins in the Department of Electrical and Computer Engineering to design printed circuits on silicon chips based on insect visual system organization. These circuits will be able to resolve directional motion across a range of velocities and ambient light intensities.

Selected Recent Publications