Mice as laboratory animals.

From locating a secure home, foraging for food, running away from predators,
spatial navigation is an integral part of everyday life. Multiple brain regions work
together to form a three-dimensional representation of our environment; specifically,
place cells, grid cells, border cells & head direction cells are thought to interact and
influence one another to form this cognitive map. Head direction (HD) cells fire as the
animal moves through space, according to directional orientation of the animal’s head
with respect to the laboratory reference frame, and are therefore considered to represent
the directional sense. Interestingly, inactivation of head direction cell-containing brain
regions has mixed consequences on spatial behavior. Current methods of identifying HD
cells are limited to in vivo electrophysiological recordings in a dry-land environment. We
first developed a dry-land version of the MWM in order to carry out behavioral-recording
paired studies. Additionally, to learn about HD cells function we quantified expression of neuronal activation marker (c-Fos), and L-amino acid transporter 4 (Lat4) in neurons
found within the HD cell dense anterodorsal thalamic nucleus (ADN) in mice after
exploratory behavior in an open field, or forward unidirectional movement on a treadmill.
We hypothesize that the degree to which ADN neurons are activated during exploratory
behavior is influenced by the range of heading directions sampled. Additionally, we
hypothesize that c-Fos and Lat4 are colocalized within ADN neurons following varying
amounts of head direction exposure. Results indicate that following free locomotion of
mice in an open field arena, which permitted access to 360° of heading, a greater number
of ADN neurons express c-Fos protein compared to those exposed to a limited range of
head directions during locomotion in a treadmill. These findings suggest that the degree
of ADN neuronal activation was dependent upon the range of head directions sampled.
We observed a high degree of colocalization of c-Fos and Lat4 within ADN suggesting
that Lat4 may be a useful tool to manipulate neuronal activity of HD cells. Identifying
genetic markers specific to ADN helps provide an essential understanding of the spatial
navigation system, and supports development of therapies for cognitive disorders
affecting navigation.

Establishing appropriate animal models for the study of human memory is
paramount to the development of memory disorder treatments. Damage to the
hippocampus, a medial temporal lobe brain structure, has been implicated in the memory
loss associated with Alzheimer’s disease and other dementias. In humans, the role of the
hippocampus is largely defined; yet, its role in rodents is much less clear due to
conflicting findings. To investigate these discrepancies, an extensive review of the rodent
literature was conducted, with a focus on studies that used the Novel Object Recognition
(NOR) paradigm for testing. The total amount of time the objects were explored during
training and the delay imposed between training and testing seemed to determine
hippocampal recruitment in rodents. Male C57BL/6J mice were implanted with bilateral
dorsal CA1 guide cannulae to allow for the inactivation of the hippocampus at discrete
time points in the task. The results suggest that the rodent hippocampus is crucial to the
encoding, consolidation and retrieval of object memory. Next, it was determined that there is a delay-dependent involvement of the hippocampus in object memory, implying
that other structures may be supporting the memory prior to the recruitment of
hippocampus. In addition, when the context memory and object memory could be further
dissociated, by altering the task design, the results imply a necessary role for the
hippocampus in the object memory, irrespective of context. Also, making the task more
perceptually demanding, by requiring the mice to perform a two-dimensional to three-dimensional
association between stimuli, engaged the hippocampus. Then, in the
traditional NOR task, long and short training exploration times were imposed to
determine brain region activity for weak and strong object memory. The inactivation and
immunohistochemistry findings imply weak object memory is perirhinal cortex
dependent, while strong object memory is hippocampal-dependent. Taken together, the
findings suggest that mice, like humans, process object memory on a continuum from
weak to strong, recruiting the hippocampus conditionally for strong familiarity.
Confirming this functional similarity between the rodent and human object memory
systems could be beneficial for future studies investigating memory disorders.