Fornix Transection Impairs Learning of Randomly Changing Object Discriminations

Abstract

The hippocampus has a well established role in spatial memory, but increasing evidence points to a role in nonspatial aspects of memory. To investigate such a role, six macaque monkeys received a bilateral transection of the fornix to disconnect subcortical inputs and outputs of the hippocampus. An additional six macaque monkeys constituted an unoperated control group. To test the involvement of the hippocampus in nonspatial aspects of memory, both groups were trained postoperatively on four concurrent visual object discrimination problems, each problem having one rewarded object and one unrewarded. After acquisition to criterion of these discriminations, the monkeys learned five subsequent stages of discriminations using the same objects. In each of these stages, both the pairings of objects one with another, and the reward assignments for the objects, were randomly reassigned. In the initial acquisition stage, control and fornix animals were equally proficient in learning the discriminations. In the five reassigned stages, however, monkeys with fornix transection made on average three times as many errors as the controls in learning the discriminations. This impairment was noted even in trials where the reward assignments from the previous stage were maintained in the new stage. These findings are consistent with other recent evidence for a role beyond the spatial domain for the fornix in monkeys.

Adaptability to changes in temporal structure is fornix-dependent

“…1 and were exposed to five different delay lengths intermixed throughout the session) was not trivial because it required animals to learn about the changing temporal structure of trials, for example, in distinguishing intrafrom intertrial intervals, and in adjusting the maintenance duration from one trial to the next (e.g., from 1 sec 16 sec). Previous studies have shown that fornix transection impairs learning and memory in the temporal domain Brasted et al 2005) and the deficit here may similarly reflect an impairment in learning about temporal structure (Wilson et al 2007). Here, our findings confirmed such a prediction and provided causal evidence for previous studies which suggested that the hippocampus is involved in integrating interval duration information contained within a sequence (Barnett et al 2014).…”

Fornix transection selectively impairs fast learning of conditional visuospatial discriminations

“…This leads us to propose that the impairments in our study should be attributable to a deficit in encoding the spatio-temporal context in which associations were learned. This is consistent with other recent studies that have argued that the deficits after fornix transection in reversal learning paradigms may also be attributed to deficits in learning about temporal context (Wilson et al, 2007).…”

“…However the FNX group was less able to remember incorrect responses from further back in time than the preceding trial, as evidenced by their greater likelihood than the CON group to return back to previously unrewarded places from responses made more than one trial ago, thereby generating more nonperseverative errors. Although FNX monkeys' abilities in monitoring the most recent action remained intact, their deficits in remembering multiple stimuli chosen over extended periods of time and in monitoring earlier errors is consistent with an impairment in the processing of temporal order/context Wilson et al, 2007). It is unlikely that the impairments observed in the present study may be attributable solely to deficits in remembering information over longer periods of time because a previous study showed that fornix transected monkeys were as good as controls at recognizing stimuli irrespective of when the item was presented (i.e., early or late) in an extended list of samples .…”

“…At the conclusion of this experiment and a series of following experiments (Kwok and Buckley, 2006;Wilson et al, 2007) the animals with fornix transection were deeply anesthetized, then perfused through the heart with saline followed by formol-saline solution. The brains were blocked in the coronal stereotaxic plane posterior to the lunate sulcus, removed from the skull, and allowed to sink in sucrose-formalin solution.…”

How the primate fornix is affected by age

“…It can be assumed, however, that a loss of nerve fibers from the fornix interferes with the efferent connections from the hippocampus and it is not surprising that studies of the effects of damage to the fornix in both humans (e.g. D’Esposito et al, 1995; Gaffan 1974; Gaffan et al, 1991) and in monkeys (Gaffan et al 2001, Owen and Butler, 1981, Wilson et al 2007) have emphasized that the fornix has a role in memory, and have described amnesia as the major consequence of lesions.…”