Thesis Format
Integrated Article
Degree
Doctor of Philosophy
Program
Neuroscience
Supervisor
Martinez-Trujillo, Julio C.
Abstract
The lateral prefrontal cortex (LPFC) and the hippocampus (HPC) are two brain regions that receive inputs from association cortices, and are involved in different types of memory, short- and long-term respectively. In an attempt to discover how these regions encode visual information in a virtual environment task, I recorded neural activity from the right mid-posterior HPC of two male macaques (Macaca mulatta) and from the left LPFC of two other male macaques. Then they carried out a learning task in a virtual environment, using a joystick to navigate. I compared selectivity for specific views of task-relevant parts of the maze and found view-selective cells in both regions. Notably, during this, I was intrigued by the bursting behaviour of the HPC neurons. To investigate whether the HPC might be using a burst code, I compared task period decoding using a burst rate or a firing rate code in both regions in the same task. I found that while firing rate codes performed better in both regions, this difference was much smaller in the HPC. A contributing factor to bursting is the intrinsic property of spike frequency adaptation (SFA), and I was able to assess this property in LPFC neurons, comparing between a minimalist saccade task and our virtual environment task, as well as measuring the property directly using in vitro patch-clamp methods. I found that SFA was similar across tasks, but more pronounced in vivo than in vitro for both broad and narrow, putative pyramidal and parvalbumin-positive interneurons (which largely did not adapt in vitro). Summed up, I was able to acquire interpretable signals from the macaque brain during complex virtual navigation tasks that I was able to analyse at a variety of scales. From neurons that encode specific views, to differences in the responses that do that encoding, and finally adaptation response properties of different types of neurons.
Summary for Lay Audience
I recorded from individual neurons in two regions of the brain of macaque monkeys, the lateral prefrontal cortex (LPFC) and the hippocampus (HPC). Both these regions receive highly processed visual information and are involved in different types of memory. The monkeys used a joystick to navigate in a virtual environment presented on a screen to complete a context-object association learning task while we tracked their eye movements. I analyzed the neural activity to find neurons that increased their firing rate when they looked at a certain region of the virtual environment, but not others, which have been previously described in the HPC. I found these neurons in both areas, and there were more in the LPFC, a new discovery. Many of these neurons maintained their selectivity when task-relevant objects were changed. During analysis, I noticed that the HPC neurons fired in bursts, and wanted to see how much information I could detect if I used the burst as the event rather than individual spikes. There was much more information in HPC bursts than LPFC bursts, which I suggest is related to the critical role that the HPC plays in long-term memory. Bursts can change the strength of connections between neurons (synapses), which is critical for maintaining a memory over long periods of time. The LPFC is critical for working memory, which stores information for a short time. It is believed that it stores the information in persistent activity, carried by groups of neurons. LPFC neurons need to be flexible enough to rapidly switch to new information if a new problem presents itself. This would suggest that synaptic changes are not beneficial for this region, and indeed we found little bursting there. Finally, I explored the spike frequency adaptation (SFA) of the LPFC neurons, the decrease in activity of a neuron to a steady stimulus. This occurs in pyramidal neurons, and not fast spiking PV interneurons. We compared SFA between two different tasks, with different stimuli, and found no difference, and then compared this to SFA in brain slices, where we only found an overlap in SFA for putative pyramidal neurons, not interneurons. This thesis is a testament to the variety of analyses that can be applied to neural responses in a complex virtual environment task, with important findings on the function of neurons in both the HPC and LPFC.
Recommended Citation
Corrigan, Benjamin W., "Neural responses in the lateral prefrontal cortex and hippocampus of macaques navigating virtual environments" (2023). Electronic Thesis and Dissertation Repository. 9728.
https://ir.lib.uwo.ca/etd/9728
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