The Shepherd-Willhite Laboratory

Yale School of Medicine

Department of Neurobiology

Students and Postdoctoral fellows are encouraged to expand this list to wherever their science or their ideas take them.

While a general overview of the connectivity is known, we hypothesize that the fine details of the connections are responsible for the information processing properties of neural networks.  We are probing the connectivity relationships using transsynaptic tracing viruses.  This work has begun to shed light on how the olfactory network is wired to perform logic gating operations. Projects can include but are not limited to: anatomy, in vivo imaging and/or electrophysiology, and slice physiology in rodent model systems.

Deficits in the olfactory sense significantly precede other symptoms of Alzheimer’s disease (AD) in humans.  Using AD mouse models, we are testing if olfactory deficits are also observed in mice.  If these deficits occur, the olfactory circuit will be probed for differences in AD connectivity.

A key goal in neuroscience is to explain how the operations of a neuron emerge from sets of active channels with specific dendritic distributions. If general principles can be identified for these distributions, dendritic channels should reflect the computational role of a given cell type within its functional neural circuit. These modeling studies attempt to derive rules for how dendrites integrate information.

In vivo Neuronal Circuit Mapping

Computational modeling of dendritic function

Behavioral testing and circuit mapping of Alzheimer’s mouse models

Project List

We are engineering alphaherpesviruses to improve the specificity and utility of the circuit mapping.  These projects involve cloning, mammalian tissue culture, rodent surgery and other molecular techniques.

Genetic Engineering of Circuit Tracing  Viruses

Using a realistic modeling approach we have shown how backpropagating action potentials in the long lateral dendrites of mitral cells, together with granule cell actions on mitral cells within narrow columns forming glomerular units, can provide a mechanism to activate strong local inhibition between arbitrarily distant mitral cells. The simulations predict a new role for the dendrodendritic synapses in the multicolumnar organization  of the granule cells. This new paradigm suggests the olfactory bulb is an excellent model system to study cortical function, the principles of which may apply to neocortical columns as well.

Computational modeling of olfactory bulb circuits

Laboratory Projects

Computational Projects

Cutting edge database tools in neuroinformatics

The SenseLab Project is a long term effort to build integrated, multidisciplinary models of neurons and neural systems, using the olfactory pathway as a model. This is one of a number of projects funded as part of the  Human Brain Project whose aim is to develop neuroinformatics tools in support of neuroscience research. The project involves novel informatics approaches to constructing databases and database tools for collecting and analyzing neuroscience information, and providing for efficient interoperability with other neuroscience databases.