Removal of the hippocampus and transection of the fornix produce comparable deficits on delayed non-matching to position by rats

Aggleton, John Patrick; Keith, A.B.; Rawlins, J. N. P.; Hunt, P. R.; Sahgal, Arjun

doi:10.1016/s0166-4328(05)80325-0

Cited by 157 publications

(70 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We chose to investigate the current task using fornix transection, rather than selective hippocampal lesions. Fornix transection interrupts the subcortical inputs and outputs of the hippocampus, and has previously been shown to have equivalent effects in a number of tasks to direct lesions to the hippocampus (Aggleton et al, 1992;Wible et al, 1992;Whishaw and Jarrard, 1995), although their effects are not always identical (McDonald et al, 1997). Importantly, transection of the fornix avoids damage to any of the cortical areas surrounding the hippocampus, particularly areas of rhinal cortex, and so may be a better way to produce selective hippocampal dysfunction than direct lesions.…”

Section: Discussionmentioning

confidence: 99%

Fornix Transection Impairs Learning of Randomly Changing Object Discriminations

Wilson

Charles²,

Buckley³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

Fornix Transection Impairs Learning of Randomly Changing Object Discriminations

Wilson

Charles²,

Buckley³

et al. 2007

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…This design has also been adopted previously in delayed non-matching-tosample tests (e.g. Aggleton et al 1986, 1992, Yee and Rawlins 1994. Here, the use of a correction trial (see below) further ensured that correct choice behaviour would also be consistently guided by a win-shift strategy.…”

Section: Baseline Delayed Alternation Trainingmentioning

confidence: 99%

The glycine transporter 1 inhibitor SSR504734 enhances working memory performance in a continuous delayed alternation task in C57BL/6 mice

2008

View full text Add to dashboard Cite

Rationale Inhibition of the glycine transporter 1 (GlyT1) activity increases extra-cellular glycine availability in the CNS. At glutamatergic synapses, increased binding to the glycine-B site located in the N-methyl-D-aspartate receptor (NMDAR) can enhance neurotransmission via NMDARs. Systemic treatment of 2-chloro-N-[(S)-phenyl [(2S)-piperidin-2-yl] methyl]-3-trifluoromethyl benzamide, monohydrochloride (SSR504734), a selective GlyT1 inhibitor, is effective against social recognition impairment induced by neonatal phencyclidine treatment and enhances pre-pulse inhibition in a mouse strain (DBA/2) with intrinsic sensorimotor gating deficiency, suggesting that SSR504734 may be an effective cognitive enhancer. Objective The objective of the study was to examine if SSR504734 exhibits a promnesic effect on working memory function in wild-type C57BL/6 mice using an automatic continuous alternation task. Materials and methods Hungry mice were trained to alternate their nose pokes between two food magazines across successive discrete trials in an operant chamber in order to obtain food reward. Correct choice on a given trial thus followed a non-matching or win-shift rule in relation to the preceding trial, with manipulation of the demand on memory retention, by varying the delay between successive trials. Results Pre-treatment with SSR504734 (30 mg/kg, i.p.) improved choice accuracy when the delay from the previous trial was extended to 12-16 s. Furthermore, a dose-response analysis (3, 10, 30 mg/kg) revealed a clear dose-dependent efficacy of the drug: 3 mg/kg was without effect, whilst 10 mg/kg led to an intermediate enhancement in performance. Conclusion The present findings represent the first demonstration of the promnesic effects of SSR504734 under normal physiological conditions, lending further support to the suggestion of its potential as a cognitive enhancer.

show abstract

“…Whereas hippocampal neurotoxic lesions often leave a relatively large proportion of hippocampal neurons intact (.25% on average; see Table 1 in Murray and Mishkin 1998), fornix transection can be assured of sectioning 100% of fornical fibers in every animal so this intervention is advantageous in its consistency despite its indirect effect upon hippocampal function. Certainly, fornix transection can be as effective as hippocampal lesions in producing deficits in some tasks such as delayed nonmatching-to-position tasks (Aggleton et al 1992;Whishaw and Jarrard 1995). All licensed procedures were carried out in compliance with the United Kingdom Animals (Scientific Procedures) Act of 1986.…”

mentioning

confidence: 99%

Adaptability to changes in temporal structure is fornix-dependent

2015

View full text Add to dashboard Cite

Recognition memory deficits, even after short delays, are sometimes observed following hippocampal damage. One hypothesis links the hippocampus with processes in updating contextual memory representation. Here, we used fornix transection, which partially disconnects the hippocampal system, and compares the performance of fornix-transected monkeys with normal monkeys on two versions of a delayed-matching-to-position task with short delays. Spatial recognition memory was affected by fornix transection only when the temporal structure of the task changed across trials, while differences in motor control, motivation, perception, or short-term memory were not critical. We attributed the deficit to a compromised ability in tracking changes in task temporal structure.Fornix transection disconnects one of the major input/output pathways of the hippocampus (Saunders and Aggleton 2007). In humans, fornix damage may result in long-term memory loss in recognition (Gaffan and Gaffan 1991;Poreh et al. 2006) and recall (McMackin et al. 1995;Aggleton et al. 2000) whereas short-term/ working memory (STM) is sometimes spared (Scoville and Milner 1957;Cave and Squire 1992;Ryan and Cohen 2004). Similarly, monkeys with lesions of the hippocampal formation performed normally on a delayed nonmatching-to-sample task when the delays were short (≤15 sec) but were impaired at longer delays (.30 sec) (Alvarez et al. 1994), in keeping with the notion that the hippocampal system contributes to the recovery of contextual details in long-term memory (Tsivilis et al. 2008;Vann et al. 2009). However, other evidence has challenged this dissociation (Ranganath and Blumenfeld 2005;Kwok and Macaluso 2015). For example, lesions in the medial temporal lobe (MTL) can impair retention of information across short delays (Jeneson et al. 2012) and the hippocampus exhibits persistent activity during STM maintenance (Chein et al. 2011), indicative of a hippocampal role in STM too. Indeed, some recent neuropsychological studies associate hippocampal disruption with deficits in spatial tasks placing high demands on spatial configural processes even in the absence of any delay (Lee et al. 2005(Lee et al. , 2006, further refuting delaydependent theories.Recent studies have provided one possible account to reconcile these seemingly contradictory results. On the one hand, empirical data from animal studies link temporal order processing to an extended diencephalic-hippocampal system in both rodents and primates (Fortin et al. 2002;Charles et al. 2004), suggesting the hypothesis that hippocampal networks mediate associations between sequential events. On the other hand, human neuroimaging studies have indicated that multivoxel patterns in the hippocampus contain temporal information (Hsieh et al. 2011;Ezzyat and Davachi 2014) and that interevent associative encoding and retrieval is mediated by the hippocampus (DuBrow and Davachi 2014), suggesting that hippocampal processes may play an important role in establishing temporal relationships among events. Pertinently,...

show abstract

Removal of the hippocampus and transection of the fornix produce comparable deficits on delayed non-matching to position by rats

Cited by 157 publications

References 35 publications

Fornix Transection Impairs Learning of Randomly Changing Object Discriminations

Fornix Transection Impairs Learning of Randomly Changing Object Discriminations

The glycine transporter 1 inhibitor SSR504734 enhances working memory performance in a continuous delayed alternation task in C57BL/6 mice

Adaptability to changes in temporal structure is fornix-dependent

Contact Info

Product

Resources

About