Research Questions and Methods

 

 
 

Outstanding questions we seek to address

  • How does the activity across the hippocampus lead to the formation of a new memory?

  • How do active dendritic signals participate in the formation of a new memory and shape memory representations throughout experience?

  • Are changes in synaptic strength the physical substrate of memory storage and what are the specific plasticity rules that are engaged during learning?

  • How does inhibition, neuromodulation and glial cell activity contribute to memory formation?

  • How do the above mechanisms contribute to memory recall?

  • How do neural circuits change as memories are altered following memory recall and which circuits modulate them?

  • How does time and experience effect the underlying neural circuitry of a memory (drift dynamics) and what controls these dynamics?

  • How do rewarding and aversive experiences influence memory representations and through which circuits?

  • How does the hippocampus, particularly the dentate gyrus (DG), separate similar experiences o form distinct memories?

  • Does the DG perform pattern separation in its conical inputs and if so under what conditions?

 Research Methods We Employ

  • Behavior in immersive virtual reality worlds

  • DREADD technology for specific circuit manipulations (inhibition and excitation)

  • Computational modeling to further understand the neural data we collect, which generates new, testable hypotheses

  • A VR-Contextual fear conditioning (CFC) method developed in the lab to perform CFC in headfixed mice navigating virtual contexts

  • In vivo 2-photon functional imaging of large populations of neurons in CA1, CA3, and DG. 

  • In vivo 2-photon functional imaging of dendrites, spines and axonal inputs from intra- and extra-hippocampal circuits such as contralateral CA3, VTA, LC, and thalamus.

  • 1-photon optogenetic stimulation and inhibition of genetically defined neurons and circuits.

  • 2-photon optogenetic stimulation and inhibition of experimenter defined neurons and dendrites