Integrated Calendar

Denise Cai:
Linking memories across time
The compilation of memories, collected and aggregated across a lifetime defines our human experience. My lab is interested in dissecting how memories are stored, updated, integrated and retrieved across a lifetime. Recent studies suggest that a shared neural ensemble may link distinct memories encoded close in time. Using in vivo calcium imaging (with open-source Miniscopes in freely behaving mice), TetTag transgenic system, chemogenetics, electrophysiology and novel behavioral designs, we tested how hippocampal networks temporally link memories. Multiple convergent findings suggest that contextual memories encoded close in time are linked by directing storage into overlapping hippocampal ensembles, such that the recall of one memory can trigger the recall of another temporally-related memory. Alteration of this process (e.g. during aging, PTSD, etc) affect the temporal structure of memories, thus impairing efficient recall of related information.

Tristan Shuman:
Breakdown of spatial coding and interneuron synchronization in epileptic mice
Temporal lobe epilepsy causes severe cognitive deficits yet the circuit mechanisms that alter cognition remain unknown. We hypothesized that the death and reorganization of inhibitory connections during epileptogenesis may disrupt synchrony of hippocampal inhibition. To test this, we simultaneously recorded from CA1 and dentate gyrus (DG) in pilocarpine-treated epileptic mice with silicon probes during head-fixed virtual navigation. We found desynchronized interneuron firing between CA1 and DG in epileptic mice. Since hippocampal interneurons control information processing, we tested whether CA1 spatial coding was altered in this desynchronized circuit using a novel wire-free Miniscope. We found that CA1 place cells in epileptic mice were unstable and completely remapped across a week. This place cell instability emerged ~6 weeks after status epilepticus, well after the onset of chronic spontaneous seizures and interneuron death. Finally, our CA1 network model showed that desynchronized inputs can impair information content and stability of CA1 place cells. Together, these results demonstrate that temporally precise intra-hippocampal communication is critical for spatial processing and hippocampal desynchronization contributes to spatial coding deficits in epileptic mice.