Timing and hippocampal information processing

Abstract

Timing is a key component in hippocampal encoding of space. I will discuss three lines of work related to this theme. First, I will describe the fine-timescale characteristics of single neurons in hippocampal subregion CAl, where theta oscillations organize groups of neurons into orderly sequences. While theta was once thought to be synchronized throughout CAl, it was recently shown instead to be offset in time along the long axis of the hippocampus. Considering distant pairs of neurons, our fundamental sequence spiking property may instead be systematically staggered by these offsets in the rhythms that pace them. I tested the impact of theta wave time offsets by recording place cell spike sequences from groups of neurons in distant parts of CAl, and found that place cell sequences more closely coordinate with each other than the underlying theta oscillations do. In regions that differ from one another by 13 milliseconds of theta delay, place cell sequences are typically aligned to within 5 milliseconds. This raises the possibility that theta wave offsets serve another purpose, perhaps timing the communication with brain areas connected to different parts of CAl, while compensatory mechanisms are in place to preserve the fine temporal alignment of place cell spatial information. Second, I will describe a tool for closed-loop experiments using information decoded from hippocampal ensembles. Place cell activity is typically extracted and analyzed only after an experiment has ended. But interrogating the timing of hippocampal information, enhancing or interfering with it, requires decoding that information immediately. I will discuss some of the difficulties and the eventual implementation of a system capable of sequence time-scale position decoding and then survey the future experimental applications.