Anterior thalamic-retrosplenial pathways for memory: uncovering a network for theta, head direction and position processing

Many studies have examined head direction (HD) cells along the main circuitry comprising the anterodorsal thalamus (AD) and retrosplenial cortex (RSC). However, little is known about how another region directly upstream of RSC, the anteroventral thalamus (AV), encodes directional information and contributes to RSC processing. By virtue of their anatomical connections and neurophysiological properties, AD and AV are considered to mediate a HD and a theta propagating system to hippocampal formation. In collaboration with University College London (UCL), I recorded single units and oscillatory local field potentials (LFP) from the RSC and AV of freely moving rats as a step towards understanding the function of this thalamocortical pathway.
The work done in this thesis is divided into three experiments. Experiment 1 investigated how the two RSC subregions, granular and dysgranular (gRSC; dRSC), differ with respect to their electrophysiology and thalamic connectivity. The gRSC is more closely connected to the hippocampal formation, in which theta-band LFP oscillations are prominent. The main finding is that there is functional and anatomical segregation within the AV-RSC circuit, whereby only gRSC contains a subpopulation of non-directional cells with spiking activity strongly entrained by theta oscillations. Results suggest the existence of two distinct but interacting RSC subcircuits: one connecting dorsomedial AV (AVDM) to gRSC that may comprise part of the hippocampal cognitive system, and the other connecting ventrolateral AV (AVVL) to both RSC subregions that may link hippocampal and perceptual regions.
Experiment 2 recorded from the two AV subfields to investigate what information is encoded in the firing of AV neurons and whether anatomically-segregated AV projections to RSC could help to explain differences in theta coding between gRSC and dRSC. The main finding is that AV contains multiple functional cell types distributed differentially across the two AV subfields and showing differential responses to theta, orientation and spatial locational, namely place cells, non-rhythmic HD cells and Theta-by-HD cells. A subset of these cells additionally encodes the speed of rotational and translational head movements.
Experiment 3 evaluated the firing of AV cells across trials in light and darkness, showing that most HD and place cells maintained their selectivity of firing in both conditions. However, there was an increase in drift in darkness, which was stronger for Theta-by-HD than non-rhythmic HD cells. Theta-by-HD cells did not show coherence of firing during drifting, in contrast to the high rotational coherence expressed by non-rhythmic HD cells. This indicates the presence in AV of two separate HD networks: a global continuous HD network attractor, centered in AVDM, and a theta-modulated HD network, centered in AVVL, that does not necessitate attractor connectivity to generate directional tuning.
A topographical organization of HD and place cells within AVDM and AVVL reinforces the notion that the AV-RSC circuitry comprises two anatomically and functionally distinct subcircuits that are differentially involved in the exchange of HD information (via AVDM-gRSC) and in the integration, within a theta frequency range, of HD information with other spatial and sensory representations (via AVVL-dRSC): a convergence that provides foundations for downstream spatial representations in cortical regions. Overall, results emphasize a new, crucial role of AV within the broader neuronal circuitry supporting memory and navigation.

Advisor: Jeffery, K
Mitchell, A
Murphy, R