Asgeirsdottir, Herborg Nanna

Considerable research has been carried out to establish a rodent model for the
study of human memory, yet functional similarities between the species remain up for
debate. The hippocampus, a region deep within the medial temporal lobe of the
mammalian CNS, is critical for long-term episodic memory. Projections from the medial
entorhinal cortex convey spatial/contextual information, while projections from the
lateral entorhinal cortex convey item/object information to the hippocampus. The
functional significance of these parallel projections to the rodent hippocampus has been
suggested to support spatial processing, while the same projections to the human
hippocampus support spatial and non-spatial memory. Discharging in a location-specific
manner, hippocampal place cells contribute to spatial memory; however, evidence for
neuronal correlates of non-spatial object memory has not been fully defined. The current
experiments were designed to address the following questions, while utilizing
electrophysiology, functional inactivation during a novel behavioral task, and immunohistochemistry. Is the memory for objects hippocampal-dependent, solely due to
the location of the object, or are objects represented within hippocampal activity
independent of location? To tease apart spatial and non-spatial processing by the
hippocampus, the spatial aspects of 3D objects were enhanced by utilizing movement. A
novel discriminatory avoidance task, Knowing Your Enemy, was adapted from an Enemy
Avoidance task to test true object memory in mice. Current findings support the notion
that object-associations acquisition depends upon a specific context. Retrieval of such
object-associations is not context-dependent, yet remains sensitive to temporary
inactivation of the CA1 region of the dorsal hippocampus. The avoidance impairments
observed following hippocampal inactivation were shown to not be a result of reduced
anxiety. Immunohistochemical marker expression suggests that the CA1 region was
highly active during object exposures, yet the hippocampal system responded
differentially to moving and to stationary objects. Recordings of CA1 neurons yielded
non-bursting object-related activity during object exploration, and place cell activity
remained unaffected in the presence of moving objects; supporting independent, yet
simultaneous processing of spatial and non-spatial information within the hippocampus.
Together, the current findings support the notion that the CA1 region of the rodent
hippocampus processes object-related information, independent of spatial information.

The rodent hippocampus is an essential neural substrate for spatial memory. This
functional capacity is considered to rely upon a cognitive map that represents the location where
relevant non-spatial items or objects are encountered and where specific events occur within a
contextual or spatial reference frame. Place cell activity recorded from CA1 pyramidal neurons
of the dorsal hippocampus of freely moving rodents is influenced by distal and proximal cues or
items within an environment, and increases when objects are placed into a familiar arena.
Recently, the CA1 region of the rodent dorsal hippocampus was shown to play a vital role in
object-in-context memory, and object memory independent of context; findings consistent with
the cognitive map view. Here, we tested the influence of 3D objects on the spatial firing
properties of CA1 neurons, since object-specific neuronal activity has not yet been fully
established in mouse hippocampus. In vivo extracellular recordings from intermediate dorsal
CA1 yielded simultaneous recordings of place cells and a pyramidal neuron demonstrating
object-specific activity over two consecutive sessions with objects present. Higher frequency
object-specific activity was recorded from the same mouse again 3 weeks later during a
comparable task. Object-specific activity was observed only when the mouse explored objects in
the arena, and was independent of spatial location or object identity. Recordings from more distal
region of dorsal CA1, which receives input from proximal CA3, yielded two additional neurons
that demonstrated comparable object-related activity. These results further support the
involvement of the rodent hippocampus in non-spatial object memory.

The rodent hippocampus is critical for processing spatial memory but its contribution to non-spatial, specifically object memory is debated. The cognitive map theory of hippocampal function states that the hippocampus stores relationships of goal locations (places) to discrete items (objects) encountered within environments. Dorsal CA1 place cells were recorded in male C57BL/6J mice performing three variations of the novel object recognition paradigm to define "object-in-context" representation of hippocampal neuronal activity that may support object memory. Results indicate, (i) that place field stability is higher when polarizing environmental cues are provided during object recognition; (ii) hippocampal place fields remain stable throughout the novel object recognition testing without a polarizing cue; and (iii) time dependent effects on stability when objects were dissociated from the context. These data indirectly support that the rodent hippocampus processes object memory, and challenge the view that "object-in-context" representations are formed when mice perform novel object recognition task.