Elsevier

Behavioural Brain Research

Volume 269, 1 August 2014, Pages 37-43
Behavioural Brain Research

Research report
Dorsal hippocampus inactivation impairs spontaneous recovery of Pavlovian magazine approach responding in rats

https://doi.org/10.1016/j.bbr.2014.04.014Get rights and content

Highlights

  • Spontaneous recovery was observed for a distally but not recently extinguished cue.

  • Dorsal hippocampal inactivation with muscimol eliminated spontaneous recovery.

  • Dorsal hippocampus appears involved in controlling extinction by temporal context.

Abstract

Destruction or inactivation of the dorsal hippocampus (DH) has been shown to eliminate the renewal of extinguished fear [1], [2], [3], [4]. However, it has recently been reported that the contextual control of responding to extinguished appetitive stimuli is not disrupted when the DH is destroyed or inactivated prior to tests for renewal of Pavlovian conditioned magazine approach [5]. In the present study we extend the analysis of DH control of appetitive extinction learning to the spontaneous recovery of Pavlovian conditioned magazine approach responding. Subjects were trained to associate two separate stimuli with the delivery of food and had muscimol or vehicle infused into the DH prior to a single test-session for spontaneous recovery occurring immediately following extinction of one of these stimuli, but one week following extinction of the other. While vehicle treated subjects showed more recovery to the distally extinguished stimulus than the proximal one, muscimol treated subjects failed to show spontaneous recovery to either stimulus. This result suggests that, while the DH is not involved in the control of extinction by physical contexts [5], it may be involved when time is the gating factor controlling recovery of extinguished responding.

Introduction

When the rat is given repeated temporal pairings of a conditioned stimulus (CS) and an unconditioned stimulus (US), for example a tone and food, presentations of the CS elicit conditioned responding (CR), such as magazine approach. The learning that CS–US pairings produces is commonly understood in terms of new associative connections developing between neural representations of the CS and US. During an extinction phase, repeated nonreinforced presentations of the CS attenuate the propensity of CSs to elicit CRs. However, subjects tested following a delay between extinction and the test session (e.g., 1 week) show a reemergence of CRs in response to the CS – an effect referred to as spontaneous recovery [6], [7]. Some theoretical approaches to Pavlovian learning (e.g., [8]) assume that extinction only partially weakens the CS–US association, and the presence of spontaneous recovery confirms that the original learning was not completely abolished [9]. However, other findings suggest that under some circumstances associations can survive extinction treatments fully intact [10], [11] and this result challenges the assumption that extinction results in at least partial weakening of the underlying CS–US association. Given such findings together with other key results reported in the literature (e.g., [12]), other mechanisms (e.g., contextual occasion setting, acquired context inhibition, attention decrements to the CS, inhibitory stimulus-response associations) are also currently thought to play a critical role in explaining extinction [9], [13], [14], [15].

While the study of extinction has exploded in recent years, much of this work has focused on the molecular mechanisms involved in response loss. Consequently, not as much attention has been devoted to the study of the neural mechanisms of related phenomena, like spontaneous recovery. To account for spontaneous recovery at the psychological level, many mechanisms have been proposed (reviewed by Robbins [16]). For example, Pavlov [6] suggested that a CS-focused “internal inhibition” process develops during extinction and may be more labile than an excitatory learning process that develops during initial training. If so, this more labile process would dissipate more completely over time, and this would lead to spontaneous recovery.

Another explanation of spontaneous recovery is that it is a special form of “renewal” [17], [18], [19], [20]. The renewal effect refers to the finding that extinguished conditioned responding recovers when the CS is tested outside of the extinction context (e.g., [21]). That renewal and spontaneous recovery may be related is suggested by the fact that spontaneous recovery and renewal combine additively to test performance when the two are manipulated in the same experiment [22]. In order to account for the renewal effect, Bouton [18], [19] suggested that during extinction training new inhibitory learning develops, and, further, that the extinction context gates the expression of this inhibitory learning through a “negative occasion setting” process (e.g., [48], [49], [50]).

Bouton [17], [18], [19], [20] extended this analysis to explain spontaneous recovery by assuming that the time at which extinction takes place is processed by the animal as a type of context cue. Accordingly, spontaneous recovery occurs because the delay between extinction and test removes the organism from the temporal context of extinction, and, therefore, it removes the negative occasion setting that the temporal extinction context engages. Thus, while changes in physical contexts are responsible for renewal after extinction, the passage of time involves a change in temporal contexts and this promotes spontaneous recovery.

Neurobiologically focused studies of fear conditioning have begun to identify structures in the brain that are important for extinction and renewal phenomena and resemble the kind of modulatory mechanisms suggested by Bouton [23], [24], [25]. In particular, investigations of the renewal effect have suggested that the dorsal hippocampus (DH) is crucial for the expression of context-dependent extinction [1], [2], [3], [51]. When the DH is inactivated (and in some cases destroyed) prior to testing, differences in fear recovery to the CS across different contexts are no longer observed. These findings are commonly understood as implying that the DH is involved in the contextual modulation of extinction. However, while most of the supporting evidence comes from fear conditioning studies, Campese and Delamater [5] have shown recently that inactivation or destruction of the DH does not impair ABA or ABC renewal in an appetitive magazine approach task with rats. While these results conflict with the findings from the fear conditioning literature on DH function, it is worth noting that there have been no investigations of the role of the DH in spontaneous recovery either in aversive or appetitive tasks. Given our earlier findings of no effect on appetitive renewal, we may anticipate no effect of DH inactivation on appetitive spontaneous recovery as well. However, this presupposes that the neural networks mediating spontaneous recovery and renewal are one and the same, and this is unlikely, especially if temporal and physical contexts are differentially involved in these two phenomena.

In the present study the role of the DH was determined by inactivating the structure prior to a test for spontaneous recovery involving two stimuli, one extinguished proximally to the test, the other distally, as a within-subject manipulation. The design used here (see Table 1) was suggested by Rescorla [7] and ensures that both stimuli are tested in the same session, eliminating potential differences in various subject factors at the time of test (e.g., general activity differences, maturational changes). One of the stimuli (S1) was conditioned for 3 days and then extinguished in a single session. Following a three-day break period a second stimulus (S2) similarly was conditioned for 3 days and then extinguished in a single session. Immediately following the S2 extinction session, subjects were removed from the chambers and either muscimol or vehicle was infused into the DH 15 min prior to being returned for a test session with both S1 and S2. Control subjects are expected to show more recovery to S1 than S2 because the test occurs outside of the temporal extinction context of S1 (one-week following S1 extinction), but within the temporal extinction context of S2 (immediately after the S2 extinction session). If the DH is important for temporal modulation of extinction, subjects with compromised DH function would be anticipated to show impaired spontaneous recovery, i.e., low levels of responding to both S1 and S2 during the test.

Section snippets

Experimental subjects

Subjects were 32 experimentally naïve Long–Evans male rats weighing between 295 g and 346 g at the start of the study. The subjects were bred and housed in standard clear-plastic tubs 10.5 in. × 19 in. × 8 in. with woodchip bedding within a colony room on a 14:10 light:dark schedule. Subjects had free access to water while in their home tubs and were maintained within a ±5 g range of their target weights with supplemental feedings of home cage chow given after experimental sessions on a given day. The

Results

Out of the 32 subjects that started this study, 7 were not included in the data. Five of the subjects reacted in a highly abnormal way to the infusions just prior to the test session. Specifically, rats either rolled over onto their backs repeatedly or they became very slow in their movements and were generally inactive. Two subjects from the control group and 3 subjects from the muscimol group were excluded due to these problems. The other two animals were excluded due to inaccurate cannula

Discussion

Subjects infused with the saline vehicle prior to the test session displayed more recovery of magazine approach CRs to S1 than to S2. This result is consistent with previous findings of spontaneous recovery in this within-subjects experimental design [7]. Subjects infused with muscimol, however, failed to display such differences. These results suggest that the DH plays a role in spontaneous recovery in an appetitive task. However, the exact role is unclear.

One rather trivial explanation for

Acknowledgments

The research reported here partially fulfilled the requirements for the degree of PhD awarded to VDC by the City University of New York. The research was supported by National Institute of Mental Health (MH 065947), National Institute on Drug Abuse (DA 034995) grants awarded to ARD, and City University of New York graduate student research awards to VDC.

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