Lora, Joan C.

We recently reported that male C57BL/6J mice navigate in spatial tasks, such as the
Morris water maze MWM, by swimming in a particular direction to a location relative to poolbased
cues, rather than to an absolute location defined by room-based cues. Neural mechanisms
supporting this bias in rodents for relative responding rather than absolute responding in spatial
tasks are not yet understood. Anterior thalamic neurons discharge according to the current
directional heading of the animal. The contribution of head direction HD cell activity to
navigation has been difficult to elucidate. Selective inactivation of anterior thalamic nuclei ATN
by microinfusion of muscimol or fluorophore-conjugated muscimol caused a near complete shift
in preference from relative to absolute responding. Interestingly, inactivation of the dorsal CA1
region of the hippocampus did not affect relative responding. A land based version of the MWM
has been developed to permit the recording of anterior thalamic HD cells during spatial search
behavior. These experiments have been conducted to further examine the contribution of the HD
cell activity to relative responding during spatial navigation.

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.