Project Summary:
The encoding and consolidation of hippocampus-dependent memories requires temporal coordination of
pyramidal neurons in the CA1 region. Specifically, populations of pyramidal neurons organize into sequences
representing experience during theta and sharp-wave ripple oscillations. Disruption of the temporal coordination
of pyramidal neuron spikes during SWRs, as occurs in pathologies such as epilepsy, results in memory deficits.
The cellular and synaptic mechanisms underlying pyramidal neuron spike timing during SWRs with mnemonic
functions are largely unknown.
Local interneurons, via GABAergic inhibition, are known to regulate CA1 pyramidal neuron spike timing
in SWRs. However, there are approximately twenty types of such interneurons, each with distinct anatomy and
physiology. How each of these interneurons contributes to spiking activity and memory is unknown. The
interneurons hypothesized to have the most precise control over pyramidal neuron spike timing are the axo-
axonic (or chandelier) cell, which exclusively synapses directly onto the axon initial segment (AIS), and basket
cells which densely synapse on the soma. The functions of these cells in SWR dynamics, replay and spatial
memory formation have remained poorly understood, as there have been no reliable markers to genetically
access these neurons. In vivo investigations into the effects of axo-axonic and basket cells on pyramidal neuron
dynamics in SWRs, replay and their role in spatial memory formation is thus needed.
In this proposal, we aim to investigate the role of axo-axonic and basket cells in mnemonic functions of
hippocampal circuits, specifically SWRs and replay, and spatial memory formation. Cre drive lines combined
with viruses encoding Cre-dependent opsins enable us to manipulate specific interneuron activity in behaving
animals. The overarching goal of this proposal is to understand how the unique physiology of axo-axonic and
basket cells controls hippocampal circuit activity and pyramidal neuron coordination in network oscillations in
support of spatial memory formation.