Michael R. Hunsaker

The role of hippocampal subregions in detecting spatial novelty.

Previous literature suggests that the hippocampus subserves processes associated with the encoding of novel information. To investigate the role of different subregions of the hippocampus, the authors made neurotoxic lesions in different subregions of the dorsal hippocampus (i.e., CA1, dentate gyrus [DG], or CA3) of rats, followed by tests using a spontaneous object exploration paradigm. All lesion groups explored normally an object newly introduced in a familiar location. However, when some of the familiar objects were moved to novel locations, both DG and CA3 lesion groups were severely impaired in reexploring the displaced objects, whereas the CA1 lesion group was only mildly impaired in reexploration. The results suggest that the DG-CA3 network is essential in detecting novelty for spatial, but not for individual object, information.

The interactions and dissociations of the dorsal hippocampus subregions: How the dentate gyrus, CA3, and CA1 process spatial information.

Several studies have demonstrated the significance of a spatial cognitive map and its role for guided and accurate navigation through the environment. Learning and recalling spatial knowledge depends upon proper topological and metric spatial information processing. The present objectives are to better characterize the role of the hippocampus for processing topological and metric spatial information. Rats with dorsal hippocampal subregional lesions (dDG, dCA3, dCA1) were tested on a previously established metric task and topological task. The results of the present study suggest that dCA1, but not dDG or dCA3, mediates topological memory. Furthermore, dDG, dCA3, and dCA1 mediate metric memory. Dorsal DG is required for spatial information processing via pattern separation or orthogonalization of sensory inputs to generate metric representations. Dorsal CA3 and dCA1 then receive these metric representations transmitted from dDG along the trisynaptic loop. The present data add to a growing body of literature suggesting a diversity of function among the hippocampal subregions.

The role of the dentate gyrus, CA3a,b, and CA3c for detecting spatial and environmental novelty

It has been suggested that the dentate gyrus (DG) and CA3 cooperate to efficiently process spatial information. The DG has been proposed to be important for fine spatial discrimination, and the CA3 has been proposed to mediate larger scale spatial information processing. To evaluate the roles of the DG and CA3a,b for spatial processing, we developed a task that measures responses to either overall environmental novelty or a response to more subtle changes within the environment. Animals with lesions to the DG showed impaired novelty detection for both environment as well as smaller changes in the environment, whereas animals with lesions to CA3a,b showed no such deficits. A closer look at the lesions suggested that the CA3 lesions included only CA3a and CA3b, but spared CA3c. To test the role of the spared CA3c region, animals with selective lesions to CA3c that spared CA3a,b were run on the same task and showed an intermediate pattern of deficits. These results suggest that the DG is critical for spatial information processing. These data also suggest that CA3 is a heterogeneous structure, with CA3c lesioned animals showing greater spatial processing deficits than CA3a,b lesioned animals. These findings extend our knowledge of hippocampal function and need to be accounted for in future computational models.

The operation of pattern separation and pattern completion processes associated with different attributes or domains of memory

Pattern separation and pattern completion processes are central to how the brain processes information in an efficient manner. Research into these processes is escalating and deficient pattern separation is being implicated in a wide array of genetic disorders as well as in neurocognitive aging. Despite the quantity of research, there remains a controversy as to precisely which behavioral paradigms should be used to best tap into pattern separation and pattern completion processes, as well as to what constitute legitimate outcome measures reflecting impairments in pattern separation and pattern completion. This review will discuss a theory based on multiple memory systems that provides a framework upon which behavioral tasks can be designed and their results interpreted. Furthermore, this review will discuss the nature of pattern separation and pattern completion and extend these processes outside the hippocampus and across all domains of information processing. After these discussions, an optimal strategy for designing behavioral paradigms to evaluate pattern separation and pattern completion processes will be provided.

Dissociations Across the Dorsal-Ventral Axis of CA3 and CA1 for Encoding and Retrieval of Contextual and Auditory-Cued Fear

The present study was designed to dissociate the roles of dorsal CA3, dorsal CA1, ventral CA3, and ventral CA1 in contextual and auditory-cued classical fear conditioning. Rats received excitotoxic lesions of dorsal CA3, dorsal CA1, ventral CA3, or ventral CA3 prior to acquisition of classical fear conditioning. Dorsal CA3 and dorsal CA1, but not ventral CA3 or ventral CA1, lesions caused a deficit for the acquisition of contextual fear. Dorsal CA1, ventral CA3, and ventral CA1, but not dorsal CA3, lesions caused deficits for the retrieval/expression of contextual fear when tested either 24 or 48h after encoding. Ventral CA3, but not dorsal CA3, dorsal CA1, or ventral CA1, lesions caused a deficit for retrieval of auditory-cued fear when tested either 24 or 48h after encoding. The data suggest that dorsal CA3 mediates encoding of contextual fear, whereas ventral CA3 mediates retrieval of contextual fear. The data also suggest that dorsal CA1 mediates encoding and retrieval of contextual fear, whereas ventral CA1 mediates only the retrieval of contextual fear.

Dissociations of the medial and lateral perforant path projections into dorsal DG, CA3, and CA1 for spatial and nonspatial (visual object) information processing.

Medial perforant path plasticity can be attenuated by 2-amino-5-phosphonovaleric acid (APV) infusions, whereas lateral perforant path plasticity can be attenuated by naloxone infusions. The present experiment was designed to evaluate the role of each entorhinal efferent pathway into the dorsal hippocampus for detection of spatial and nonspatial (visual object) changes in the overall configuration of environmental stimuli. Dorsal dentate gyrus infusions of either APV or naloxone attenuated detection of a spatial change, whereas only naloxone infusions disrupted novel object detection. Either APV or naloxone infusions into dorsal CA3 disrupted both spatial and novel object detection. APV infusions into dorsal CA1 attenuated detection of a spatial change, whereas naloxone infusions into dorsal CA1 disrupted novel object detection. These data suggest that each dorsal hippocampal subregion processes spatial and nonspatial (visual object) information from perforant path efferents in a unique manner that is consistent with the intrinsic properties of each subregion.

The role of CA1 in the acquisition of an object-trace-odor paired associate task.

This experiment was designed to determine whether adding a temporal component to an object-odor association task would recruit the hippocampus. The rats were given CA1, CA3, or control lesions prior to learning the object-trace-odor task. Rats were presented with an object for 10 s, after which the object was removed, followed by a 10-s trace period, followed by the presentation of an odor 50 cm away. If the odor and the object were paired, rats were to dig in the odor cup for a reward. If unpaired, rats were to refrain from digging. Rats that had CA1 lesions were unable to make the association, whereas rats that had CA3 lesions performed as well as controls. These results support the idea that the hippocampus is involved in forming arbitrary associations that do not necessarily involve space as long as they involve a temporal component.

Effects of ventral and dorsal CA1 subregional lesions on trace fear conditioning.

Recent lines of research have focused on dissociating function between the dorsal and ventral hippocampus along space and anxiety dimensions. In the dorsal hippocampus, the CA1 subregion has been implicated in the acquisition of contextual fear as well as in the trace interval in trace fear conditioning. The present study was designed to test the relative contributions of dorsal (dCA1) and ventral CA1 (vCA1) in trace fear conditioning. Long-Evans rats received ibotenate lesions of the ventral CA1 (n=7), dorsal CA1 (n=9), or vehicle control lesions (n=8) prior to trace fear conditioning acquisition. Results suggest dCA1 and vCA1 groups show no significant deficits during acquisition when compared to control groups. dCA1 and vCA1 both show deficits in the retention of contextual fear when tested 24 h post-acquisition (P<.05 and P<.01, respectively), and vCA1 was impaired relative to dCA1 (P<.05). This is suggestive of a graded involvement in contextual retention between the dorsal and ventral aspects of CA1. dCA1 showed no deficit for retention of conditioned fear to the tone or the trace when tested 48 h post-acquisition, whereas vCA1 did show a significant deficit for the trace interval and a slight, non-significant reduction in freezing to the tone, when compared to the control group (p<.05). Overall the data are suggestive of a graded involvement in retention of fear conditioning between the dorsal and ventral aspects of CA1, but it is likely that vCA1 may be critically involved in retention of trace fear conditioning.

Evaluating the differential roles of the dorsal dentate gyrus, dorsal CA3, and dorsal CA1 during a temporal ordering for spatial locations task.

It has been demonstrated that the dorsal CA1 subregion of the hippocampus mediates temporal processing of information, that dorsal CA3 participates in the spatiotemporal processing of memory, and the dorsal dentate gyrus (DG) mediates spatial pattern separation. A temporal ordering of spatial locations task was developed to test the role of the dorsal DG, CA3, and CA1 for the temporal processing of spatial information with either high or low levels of spatial interference. The results indicate that animals with DG lesions showed difficulty performing the task at high levels of spatial interference, but were able to perform the task well when there was low spatial interference. Animals with lesions to CA3 did not show a preference for either spatial location presented during the study phase during the preference test, suggesting impaired spatiotemporal processing. Animals with lesions to CA1 showed a preference for a later presented spatial location over the earlier, the opposite preference to that shown by control animals.

The CA3 Subregion of the Hippocampus Is Critical for Episodic Memory Processing by Means of Relational Encoding in Rats

This experiment tested the theory that the CA3 subregion of the hippocampus mediates episodic learning of arbitrary associations. The authors developed 2 tasks based on the episodic flavor-place paired-associate task described by M. Day, R. Langston, and R. G. Morris (2003): an object-cued spatial location recall task and a spatial location-cued object recall task. After rats were trained to a criterion of 80% correct on 1 of the 2 tasks, they received either a dorsal CA3 lesion or a vehicle control lesion. Control animals continued performing well on both tasks. Rats with lesions to dorsal CA3 were impaired on both tasks and performed at chance but were able to perform a nonepisodic version of the task as a control. These data suggest that CA3 mediates episodic learning of arbitrary associations as tested in the 1-trial object-cued spatial location recall and spatial location-cued object recall tasks.