|dc.contributor.author||Allison, Elizabeth Anastasia Margaret Alice||en
|dc.description.abstract||Place cells in the hippocampus fire in specific locations within an environment. The
aim of this thesis is to investigate the different inputs to the hippocampus and what
they contribute to place cell activity and performance of hippocampus-dependent
tasks. Place cell activity can also be modulated by relevant features of a task such as a
future destination or trajectory. Initial experiments investigated the origin and function
of this trajectory-dependent activity and later experiments targeted the medial
entorhinal cortex inputs to the hippocampal formation and investigated what they
contributed to place cell activity and behaviour.
The purpose of the first study was to determine whether trajectory dependent activity
occurs in CA3 in a hippocampus-dependent serial-reversal task on the double-Y-maze
and to compare it with that seen in CA1. Place cells in both CA3 and CA1 were
recorded in rats trained on a serial-reversal task on a double-Y-maze. Rats were trained
to run from a start box through two Y-junctions to one of four goal locations. After 10
trials the reward was moved to a new location, until all the boxes had been rewarded.
Previous research has found that 44% of CA1 place cells with fields in the start areas
of the maze show trajectory-dependent activity in rats trained on the task. This study
found that a similar proportion of CA3 place cells also show trajectory-dependent
activity in rats trained on this task and that this activity develops at the same time point
as the task is learned. This result suggests that trajectory-dependent activity may be
generated earlier in the circuit than CA1.
Secondly, the contribution of the nucleus reuniens (N.Re) to spatial tasks was
investigated. Previously, trajectory-dependent activity has been found to reach the
hippocampus via N.Re, however this was shown in a hippocampus-independent task.
To investigate the possible role that this input may play in behaviour, N.Re was
lesioned and animals were tested on acquisition and performance of the double-Y-maze
serial-reversal task described previously. Surprisingly, lesions had no effects on
either learning or performance. Taken together with previous data from other studies,
this suggests that trajectory dependent activity is not one unique phenomenon but is
rather multiple similar phenomena which may originate in different brain regions and
fulfil different roles in navigation depending on the demands of the task. In addition,
animals were tested on tasks involving allocentric or egocentric navigation. Results
suggest that N.Re may have a role in the selection or performance of allocentric
navigation but not egocentric navigation.
Thirdly, the role of inputs from the medial entorhinal cortex (MEC) to place cells was
investigated. Consistent with previous research, MEC lesions resulted in larger, less
precise place fields in CA1 place cells. By performing cue-rotation experiments using
either distal or proximal cues it was observed that place fields in the MEC lesion
animals were not anchored to distal cues but were either stable or anchored to other
aspects of the environment. However, place cells in the MEC lesion group still
followed proximal cues suggesting that the deficit is restricted to distal landmarks.
This suggests that the MEC may process distal landmark information allowing the use
of distal landmarks for orientation and self-location within an environment.
This thesis contributes a better understanding of the role and origins of trajectory
dependent activity as well as a novel finding that the MEC contributes information
about distal landmarks to the hippocampus.||en
|dc.contributor.sponsor||Biotechnology and Biological Sciences Research Council (BBSRC)||en
|dc.publisher||The University of Edinburgh||en
|dc.subject||medial entorhinal cortex||en
|dc.title||Exploring the roles of inputs to hippocampal area CA1||en
|dc.type||Thesis or Dissertation||en
|dc.type.qualificationname||PhD Doctor of Philosophy||en