A Role for Dorsal and Ventral Hippocampus in Inter-Temporal Choice Cost-Benefit Decision Making

model: Group₄ × (Barrier Height₆ × S₃₇)]. The ANOVA revealed a main effect of barrier height, F(5, 165) = 10.88; p < .001, but no effect of lesion group, F(3, 33) = 0.83; p = .49, and no group × barrier height interaction, F(15, 165) = 0.85; p = .62.

In summary, without the barrier in the HR arm there were no differences in HR choices between the groups. In contrast, when the 15 cm barrier was first introduced, the sham and vHPC groups significantly reduced their choice of the HR arm compared to the cHPC and dHPC groups. In subsequent blocks the vHPC and sham groups increased their HR choices and after the 20 forced trials the groups did not differ at any of the barrier heights.

Discussion

Complete (cHPC), dorsal (dHPC), and ventral (vHPC) cytotoxic hippocampal lesions all led to reduced choice of a delayed high reward (HR) in favor of an immediately available low reward (LR) (Expt 1). The combined results of postoperative stages 1 and 3 suggest deficits in the complete and both partial lesion groups. The deficits were not due to a complete inability to remember which reward size was associated with which arm of the maze. When an equivalent 10s delay was introduced in both goal arms, all rats chose the HR arm on nearly all trials (stage 2). The deficit was, however, reinstated when the inequality was reintroduced (stage 3). In contrast, when the HR-cost was in terms of physical effort required to climb a barrier, the HPC lesioned animals' HR choices, for the most part, resembled controls, although initially both cHPC and dHPC lesioned rats were in fact more inclined to climb the barrier for the HR.

This study extends the findings of Rawlins et al. (1985) in demonstrating hippocampal lesion effects on a delay based, cost-benefit decision making T maze task, using more selective, fiber sparing, cytotoxic lesions. These effects are therefore clearly hippocampal in origin and are not due to damage to fibers of passage. Furthermore, the present study used the same experimental paradigm that has previously revealed effects with OFC lesions (Rudebeck et al., 2006). The impulsivity displayed by the hippocampal lesioned animals in postoperative stage 1 appeared similar, at least in some respects, to that seen with orbitofrontal lesions (Rudebeck et al., 2006). The present results also extend the findings of Rawlins et al. (1985) in showing that when an equivalent delay was associated with both the high and low rewards, then all the lesioned rats chose the larger reward on the majority of trials. Therefore, the effect of hippocampal damage was not due to a complete inability to use short- or intermediate-term memory to bridge the spatiotemporal discontiguity between what the animal did at the choice point and the size of the reward obtained.

Furthermore, the present results suggest that the HPC is involved in delay but not effort-based decision making tasks. However, they should be interpreted cautiously as training for the delay task was carried out preoperatively whereas all training for the effort task was postoperative, and occurred after postoperative testing on the delay task. Further experiments, in which separate groups of rats are trained preoperatively on the effort task and then given hippocampal lesions, are required to fully resolve this issue (Rudebeck et al., 2006; Walton et al., 2002). Furthermore, it is interesting to note that both the cHPC and dHPC groups were in fact initially more willing to climb the barrier than controls and vHPC lesioned rats. In fact, rats in the cHPC group chose to climb the barrier on 97% of trials during the first three blocks after the barrier was first introduced compared to 53% in the sham group. The reason for this effect is not immediately obvious. One possible account is that rats exhibit a neophobia toward the barrier when it is first introduced, and that this neophobia is reduced in animals with hippocampal lesions (Bannerman, Deacon, Offen, Friswell, Grubb, & Rawlins, 2002). However, reduced neophobia is associated with ventral but not dorsal hippocampal damage, and therefore this explanation seems unlikely. Alternatively, it is possible that the initial barrier performance of the cHPC and dHPC rats was due to perseveration. Both of these groups of rats continued to choose the HR arm, as in the previous, no-barrier condition, whereas both sham and vHPC rats shifted their behavior and increased their number of LR arm choices. However, a general increase in perseveration in HPC lesioned animals cannot account for the dataset as a whole; for example, in the delay task it is the lesioned animals (cHPC, dHPC and vHPC) and not the shams that shift their behavior (Expt 1, stages 1 and 3). Therefore, an account based on increased perseveration also seems unlikely. Interestingly, there is previous evidence that rats with HPC lesions are willing to work harder for food reward (Schmelzeis & Mittleman, 1996). HPC lesioned rats showed a profound increase in the breakpoint when trained on an operant progressive ratio 10 schedule of reinforcement, in which they were required to exert progressively more effort (increased number of lever presses) to obtain successive reinforcers. The present results suggest that this effect may be attributable to cell loss in the dorsal subregion of the HPC.

The present results also suggest an important role for both dorsal and ventral hippocampus in the neural circuitry that underlies decision making on the intertemporal choice (delay) task. This result is consistent with our prediction that the vHPC is a critical subregion for performance on the delay based, cost-benefit decision making task. However, the effect of dHPC lesions on this task was not necessarily as predicted on the basis of the anatomical segregation of HPC-OFC connections.

Previous studies have suggested a preferential role for dHPC in spatial memory tasks, whereas the vHPC has been implicated in aspects of fear and/or anxiety (Bannerman et al., 2004). Both of those findings are entirely consistent with the anatomical connections of the hippocampus along the septotemporal axis (Witter & Amaral, 2004). The present demonstration that vHPC lesions disrupt performance on an intertemporal choice task, is also consistent with the anatomical connectivity between vHPC and OFC (Jay & Witter, 1991), and the recent demonstration that OFC lesioned rats also choose impulsively on the same T maze task (Rudebeck et al., 2006). However, the present results also suggest a role for the dorsal hippocampus, which although possibly less pronounced initially (Expt 1, stage 1), is clearly apparent when the original reward contingencies were later reinstated in Expt 1, stage 3. Collectively, these results suggest that the OFC and HPC contribute to an extended neural circuitry underlying intertemporal choice, cost-benefit decision making, which presumably also includes brain areas such as the nucleus accumbens and basolateral amygdala (Cardinal, Pennicott, Sugathapala, Robbins, & Everitt, 2001; Pothuizen, Jongen-Relo, Feldon, & Yee, 2005; Winstanley, Theobald, Cardinal, & Robbins, 2004).

Importantly, the effects of vHPC lesions on the intertemporal choice T maze task in the present study are in contrast to the lack of effects on classical spatial memory tests, such as the Morris watermaze (Moser et al., 1995), and also the spatial working memory version of the T maze paradigm (Bannerman et al., 1999; Hock & Bunsey, 1998). We have argued previously for a preferential role for vHPC on tasks which have a potential defensive component (Bannerman et al., 2004). For example, vHPC lesions reduce freezing during fear conditioning (Maren & Holt, 2004; Richmond et al., 1999) and have anxiolytic effects on unconditioned tests of anxiety (Bannerman et al., 2002; Kjelstrup et al., 2002; McHugh et al., 2004). The present results suggest that the effects of ventral lesions go beyond tasks with a defensive component. However, it is still possible that the vHPC lesion effect on the present task reflects an aversive component associated with the frustration of the delay to reinforcement in the HR arm. Normal animals might form an association between the aversiveness of the delay period and the larger reward (“counterconditioning”). If the vHPC lesioned rats do not perceive the delay as aversive in the same way as controls then this counterconditioning may not occur.

Alternatively, the effects of complete and partial HPC lesions on the delay task could still be explained by a subtle memory deficit. As pointed out previously, HPC lesioned rats were not completely unable to remember which reward size was associated with which arm of the maze: in the second stage of postoperative testing in Experiment 1, all groups preferred the HR arm when the 10s delay was present on both the HR and LR arms. Nevertheless, an account in which the memory trace is merely attenuated in HPC lesions rats might still suffice. It is thus possible that the failure of HPC lesioned animals to choose the delayed HR option during stage 1 and stage 3 reflects a reduced (rather than completely impaired) ability to bridge the delay and associate the HR outcome with the appropriate memory of what happened at the choice point. Such an account might still be consistent with the view that the hippocampus acts as a temporary or intermediate memory store for information, allowing animals to form associations across temporal discontiguities (Rawlins, 1985; Schmitt et al., 2004). Furthermore, this might also explain why HPC lesioned rats shift to choosing the HR when the 10s delay is present on both arms (Expt 1, stage 2): the memory trace attenuation then applies equally to either choice but is associated with rewards of different sizes.

A further alternative explanation is that the change in responding in HPC lesioned rats could reflect a specific impairment in the processing of temporal information associated with the delay to reinforcement following the response choice. In this respect, the performance of the vHPC rats on the classical, rewarded alternation T maze paradigm might be informative. Ventral HPC lesioned rats display absolutely no impairment on this spatial working memory task (Hock & Bunsey, 1998; Bannerman et al., 1999), even when there is a substantial delay (600s) between the sample run and the choice run of each trial (Bannerman et al., 2002). This suggests intact short term memory in the vHPC rats. In contrast, there is a clear ventral HPC lesion effect in the present intertemporal choice T maze task. Consequently, it may be that an impairment in processing information about the delay to reinforcement is the crucial factor in revealing a ventral HPC lesion effect. A proposed role for the hippocampus in temporal information processing has been suggested previously. For example, studies using the peak interval procedure suggest that HPC lesions lead to an inconsistency in time estimation (Buhusi, Mocanu, & Meck, 2005; Meck, Church, & Olton, 1984). Furthermore, in many respects, the pattern of results obtained with complete and partial HPC lesions in the present study resembles the effects seen during the differential reinforcement of low rates of responding (DRL) task (Bannerman et al., 1999). Performance on the DRL task requires the animal to withhold from responding until some minimum period of time (the DRL requirement) has elapsed. As in the present study, complete, dorsal, and ventral HPC lesioned rats were impulsive, in that they were less able to withhold from lever-pressing until the prescribed delay period had passed. Interestingly, similar parallels between a delay-based decision making task and the operant DRL task have also been observed for lesions of the nucleus accumbens (Pothuizen et al., 2005). It is possible, therefore, that the effects of vHPC lesions, at least, are due to deficits in temporal information processing.

In view of our original hypothesis, and the segregation of anatomical connections between the HPC and OFC along the septo-temporal axis, the effect of dHPC lesions on the intertemporal choice T maze task might be considered surprising, although it is worth pointing out that during postoperative stage 1, the performance of the dHPC group did appear to recover to control levels by the fourth block of testing. Nevertheless, there is a clear and lasting change in behavior in the dHPC group during postoperative stage 3 in which the animals are again choosing between a delayed HR and an immediate LR, suggesting that the dHPC does make an important contribution to intertemporal choice behavior on this T maze task. One possible explanation for the dHPC lesion effects is that the task might involve integrating spatial information about the two goal arms with information about the different delays and reward sizes, and that the deficit with dHPC lesions therefore reflects the role of this subregion in spatial memory (e.g., Bannerman et al., 1999). Against this, there is no actual requirement for the animals to use an allocentric spatial solution. It is sufficient for the animals to use an egocentric strategy (turn left or turn right) when choosing a particular goal arm. Indeed, both the dHPC and cHPC lesioned rats were perfectly capable of choosing the HR when there was an equivalent delay to reinforcement in both arms (postoperative stage 2), and when there was no delay in either arm (Expt 2, no barrier condition). An alternative explanation is that both the dorsal and ventral hippocampus contribute to temporal information processing, a suggestion which is also consistent with the effects of both dHPC and vHPC lesions on the nonspatial, DRL task. It would therefore be of interest to examine the effects of lesions of both hippocampal subregions on a definitively nonspatial, intertemporal choice task (Cheung & Cardinal, 2005).

Of course, it is possible that both dHPC and vHPC lesions affect performance on the intertemporal choice task, but for different reasons. For example, there is the intriguing possibility that both lesions result in impulsivity, but that dHPC lesions do so through an inability to withhold from executing an inappropriate response (behavioral disinhibition), whereas vHPC lesioned animals are unable to properly value delayed rewards, possibly as a consequence of disrupting HPC-OFC connections. A lack of behavioral inhibition and thus an inability to withhold from responding might also of course explain the initial increased preference of dHPC and cHPC rats to climb the barrier, and is also consistent with the observation that dHPC but not vHPC lesioned rats display locomotor hyperactivity (e.g., McHugh et al., 2004). It has been suggested previously that the impulsivity construct can be fractionated into (i) impulsive action, an increase in action production and/or a failure to inhibit action execution (behavioral inhibition), and (ii) impulsive choice or decision making, which may be the result of being unable to properly value delayed rewards (Evenden, 1999; Winstanley et al., 2004). However, it is important to note that an increase in impulsive action does not necessarily lead to an increase in impulsive choice (Winstanley et al., 2004). For example, whereas OFC but not ACC lesioned rats display impulsive choice or decision making, as exemplified by their impaired performance on the T maze intertemporal choice task, ACC but not OFC lesioned rats exhibit impulsive action (Rudebeck et al., 2006). ACC rats exhibit premature motor responses (Passetti, Chudasama, & Robbins, 2002) and display locomotor hyperactivity (Rudebeck et al., 2006), but importantly they do not demonstrate impulsive choice during testing on the intertemporal choice, T maze task (Rudebeck et al., 2006). It remains uncertain, therefore, whether the effects of dHPC lesions in the present study can be fully explained by an increase in impulsive action.

Conclusions

To conclude, any account of HPC function has to explain the effects on spatial memory, anxiety, impulsive choice, and behavioral disinhibition observed after HPC damage. The present results argue that both the dorsal and ventral HPC are involved in intertemporal choice, delayed-based decision making tasks, and also support the hypothesis that the HPC plays a fundamental role in the integration of different aspects of contextual information to guide response selection (Gray & McNaughton, 2000).

Acknowledgments

This work was supported by the Wellcome Trust (Grant No. 065298). We thank Greg Daubney for his assistance with preparation of the histological material.

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