Investigating the role of the hippocampal formation in episodic and spatial memory
View/ Open
Date
27/06/2011Author
Stevenson, Cassie Hayley
Metadata
Abstract
This thesis aims to explore the two dominant functional roles of the hippocampal formation, in the
relational encoding of episodic memory and the neural representation of allocentric space, using
a combination of pharmaceutical manipulations and single-unit recording techniques in rodents.
The first part of this thesis focuses on episodic-like memory, defined by the original episodic memory
triad: ‘what-where-when’ (Tulving 1972), which enables the behavioural aspects of episodic
memory to be tested in non-human animals. Permanent neurotoxic lesions of the hippocampus
and it’s subregions were induced to assess their role in a putative episodic-like memory task developed
by Eacott and Norman (2004). In view of the difficulties encountered in successfully
demonstrating the temporal component of episodic-like memory in rats, this task tested integrated
memory for ‘what-where-which’, where the temporal component (when) was replaced with another
event specifier: context (on ‘which’ occasion). Disruption of the hippocampal circuitry led
to a specific impairment in the integration of all three event components, whereas the associative
recognition of any combination of these features in isolation was left intact. These results confirm
the hippocampal dependence of this episodic-like memory task and further reveals the necessity
of both CA3 and CA1, hypothetically due to the underlying autoassociative role of CA3 with CA1
functioning as the vital output pathway for this associated information and/or as a mismatch detector.
There has been much debate over the inclusion of the temporal component and sceptics
may argue that any such interpretations of task-dependence on episodic-like memory processing
are invalid considering the requirement for temporal processing is absent. Due to the proposal that
a temporal framework necessarily provides the foundation on which episodic memories are built,
the second chapter focuses on the development of a suitable protocol in which integrated memory
for the original ‘what-where-when’ episodic memory triad can be reliably tested.
The other main function attributed to the hippocampus was brought to light by the fascinating
revelation that it’s neurons selectively fire in different regions of an environment, termed ‘place
cells’ (O’Keefe and Dostrovsky 1971). From the numerous publications resulting from this discovery
it has emerged that place cells not only respond to the spatial features of the environment
but are also sensitive to a multitude of non-spatial features. These characteristics support the
logical assumption that the primary firing patterns of the hippocampus should underlie it’s main
purported roles, leading to speculations that they reflect episodic memory processes. The second
part of this thesis aims to examine the relationship between hippocampal cells and behaviour by
extending the work of Ainge et al. (2007a), in which a subset of hippocampal place cells were
found to encode both current and intended destination in a double Y-maze ‘win-stay’ task. The
development of these ‘goal-sensitive’ cells were initially investigated during the learning phase of
this task. An exciting pattern of results showed a strong positive correlation between the emergence
of goal-sensitive firing and behavioural performance on the task, tempting speculations that
these firing patterns may underlie spatial learning and future planning, necessary to support performance. To ensure these firing patterns were not a mere reflection of greater experience on the
maze, a second study was conducted in which the task demands changed over set periods of days.
A significant increase in the proportion of cells demonstrating goal-sensitive firing was revealed
when the protocol shifted to incorporate the spatial memory demands of the ‘win-stay’ task, with
all other parameters of the protocol remaining constant. These results support the theory that
goal-sensitive firing patterns are specifically related to the learning and memory demands of the
spatial task, not a result of increased exploration of the maze. The last of this series of studies
assessed hippocampal-dependence of this task and revealed that bilateral hippocampal lesions
induced an impairment in spatial ‘win-stay’ performance. Collectively, these experiments demonstrate
that goal-sensitive firing of hippocampal cells emerge in line with behavioural performance
in a hippocampal-dependent task and the emergence of these firing patterns are specific to the
learning and memory demands of a spatial ‘win-stay’ protocol.
The functional role of the hippocampus in allocentric spatial processing may thus underpin
it’s function in episodic memory and potentially in the imagining and planning of future events,
whereby the hippocampus provides a ‘space’ in which retrieved information can be integrated in
a coherent context to support the fluent and flexible use of information. This hippocampal function
would necessarily require visual information to be accessed, concerning the arrangement of
landmarks and cues within the environment, in association with information regarding internal
orientation and direction and this leads to the question assessed in the final part of this thesis of
where this integration occurs. Based on anatomical evidence and the current literature, the postsubiculum,
an input structure to the hippocampus, emerged as a potential site for the convergence
of sensory cues into the internally generated head direction cell and place cell networks to enable
hippocampal-dependent spatial processing. Thus, the effects of temporary pharmacological
blockade of AMPARs and NMDARs in the postsubiculum were assessed on the encoding of spatial
memory in an object recognition paradigm. The impairment revealed in the ability to recognise
novel object-place configurations demonstrates a key role for NMDAR-dependent plasticity within
the postsubiculum itself in the formation of allocentric spatial memory.
In summary, the experimental results reported in this thesis further elucidate the critical role the
hippocampal formation plays in spatial and episodic memory by combining evidence from cellular
physiology and neuroanatomy to the behaving animal and extends these findings to discuss a more
general role for the hippocampus in imagining both past and future events, in order to successfully
navigate, learn and enable past experience to influence our intended future plans and decisions.