The ventral subiculum is a critical structure in the brain's reward and memory circuitry providing integrated information from the hippocampal formation to the terminal regions of the mesolimbic dopamine system. Cannabinoid, CB1 receptors are known to be present within the pyramidal neurons of the ventral subiculum (vSub). Furthermore, I have obtained preliminary data indicating that vSub bursting pyramidal neurons respond to CB1 agonists with an enhancement in burst-induced Ca++spikes (broad low amplitude spikes). We hypothesize these Ca++ spikes to result from CB 1 receptor modulation of outward currents in the soma and apical dendrites. Dendrites have voltage-activated conductances which allows there o propagate axon or soma initiated bursts into their distal regions. I plan to first examine burst backpropagation into the dendrites using dual whole-cell somatic/dendritic recordings initiating a burst with the somatic electrode arid comparing the strength of the burst at different proximal and distal points along the dendrite. This will be combined with dendritic Ca++ imaging. Our hypothesis Is that if more transient (A-type) K+ currents exist in the distal compartments of the dendrite we should see a decrease in burst strength and then determine if a nonuniform distribution of outward K+ currents is involved in shaping the backpropagation. I will then measure CB1 modulation of the burst backpropagation and the K+ currents. Our lab has reported that sustained outward K+ currents (D-type) control the dendritic initiation of Ca++ spikes in CA1 pyramidal neurons. An increasing proximal-to- distal gradient of dendritic A-type K+ channels has been reported in CA1 pyramidal neurons and I will test for this in the vSub pyramidal neurons. Finally, I will repeatedly treat mice with cannabinoids to determine if this changes dendritic excitability using both patch-clamp and Ca++ imaging at different withdrawal time points.
| Cooper, Donald C; Moore, Shannon J; Staff, Nathan P et al. (2003) Psychostimulant-induced plasticity of intrinsic neuronal excitability in ventral subiculum. J Neurosci 23:9937-46 |
| Cooper, Donald C (2002) The significance of action potential bursting in the brain reward circuit. Neurochem Int 41:333-40 |
