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.
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.
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.
Rall, Shepherd, Reese and Brightman (1966) identified dendrodendritic synaptic interactions between mitral and granule cells, recognized to provide for the basic function of lateral inhibition in the olfactory bulb (Rall and Shepherd, 1968). We were also the first to identify the generation by odor stimulation of activity patterns in the olfactory glomeruli (Sharp, Kauer and Shepherd, 1975), since confirmed by many different methods, and to show that these could be demonstrated by high-resolution functional MRI (Xu et al, 2003). We are continuing these studies in collaboration with Dr. Justus Verhagen at the Pierce Laboratories, and Dr. Fahmeed Hyder at the Yale Imaging Center.
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.
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.