Elsevier

Brain Research

Volume 1251, 28 January 2009, Pages 185-194
Brain Research

Research Report
The role of the dorsal and ventral hippocampus in fear and memory of a shock-probe experience

https://doi.org/10.1016/j.brainres.2008.11.041Get rights and content

Abstract

The roles of the dorsal and ventral hippocampus in fear and memory are unclear. This study examined the effects of temporary inactivation of the dorsal or ventral hippocampus on unconditioned and conditioned fear, using the shock-probe test. In Experiment 1, rats received either dorsal or ventral hippocampal infusions of lidocaine or saline, before exposure to an electrified shock-probe (acquisition I). In Experiment 2, rats received lidocaine or saline infusions after exposure to the shock-probe (acquisition II). In both experiments, a retention test in the same apparatus was given 24 h later, at which time the hippocampus was no longer inactivated, and the probe was disconnected from the shock-source. Because ventral hippocampal inactivation impaired fear behaviour during acquisition, and dorsal hippocampal inactivation impaired fear behaviour (probe avoidance) during retention, we concluded that 1) the ventral hippocampus plays a role in the expression of untrained fear reactions whereas 2) the dorsal hippocampus plays a role in encoding memory of the fearful experience.

Introduction

The shock probe burying test is an experimental animal model of anxiety in which subjects are shocked by making contact with a stationary, electrified probe attached to one of the walls of a Plexiglas chamber (Pinel and Treit, 1978;Treit and Pinel, 2005). After this contact-induced shock, subjects typically engage in burying behaviour (pushing bedding material toward and/or over the probe), while simultaneously avoiding the probe. Both burying behaviour and probe avoidance are indicative of anxiety or fear in this test, since both are suppressed by anxiolytic drugs (e.g., Treit, 1990). Encoding of this aversive event is thought to be partly mediated by the hippocampus (Lehmann et al., 2005, Lehmann et al., 2006). Lesioning the hippocampus is thought to impair the rats' ability to form an association between contextual stimuli in the burying chamber and the aversive shock, as measured by subsequent burying behaviour and latency to contact a non-electrified probe during re-exposure to the testing environment (Lehmann et al., 2005).

The hippocampus plays important roles in both mnemonic and emotional functions (e.g., Bannerman et al., 2004, Degroot and Treit, 2004, Degroot and Nomikos, 2005, Engin and Treit, 2007McNaughton, 1997). The hippocampus has long been implicated in the consolidation of “explicit” or “declarative” memory (e.g., Corkin, 2002, Zola-Morgan and Squire, 1993), based on the anterograde memory deficits seen in human patients after bilateral lesions of the hippocampus (e.g., H.M; Milner 1972). Lesion studies in rats have suggested that the dorsal hippocampus is especially important in spatial memory processes (Morris et al., 1982, O'Keefe and Nadel, 1978, White and Gaskin, 2006), and in contextual fear conditioning (e.g., Bannerman et al., 2004, Lehmann et al., 2005, Oler et al., 2005). Lesions of the ventral hippocampus of rats, by comparison, block a variety of unconditioned fear reactions, including “freezing” behaviour to cat odour or electric foot-shock; avoidance of conspecifics in the social interaction test; open-arm avoidance in the elevated plus maze test; novel-food avoidance in an unfamiliar environment; light-avoidance in a two compartment, light-dark box; and defecation in the open field test (Bannerman et al., 1999, Bannerman et al., 2002, Bannerman et al., 2003, Hock and Bunsey, 1998, McHugh et al., 2004, Kjelstrup et al., 2002, Pentowski et al., 2006). Based on these findings, it has been suggested that the roles of the ventral and dorsal hippocampus in fear and memory may differ (Bannerman et al., 2004).

Tests that measure both fear and memory would seem to be particularly useful for assessing the effects of dorsal and ventral hippocampal lesions. In the shock-probe burying test, for example, both fear and memory can be monitored by first observing a rat's immediate (unconditioned) reactions to shock from the electrified probe (“acquisition”) and then, 24 h later, by observing the rat's (conditioned) reactions to an identical, non-electrified probe (“retention”). Using this paradigm, Lehmann et al. (2005) found that hippocampal-lesioned rats had shorter latencies to contact a non-electrified probe than sham-lesioned controls during a retention test 24 h after shock exposure. Hippocampal-lesioned rats also buried the probe significantly less than sham lesioned controls during the retention test. Together, these findings support the general hypothesis that the hippocampus is involved in both the behavioural reactions to, and the memory of, aversive events.

The lesions in the Lehman et al., (2005) study, however, included both the dorsal and the ventral aspects of the hippocampus. Thus, the individual roles of the dorsal and ventral hippocampus in the acquisition and retention of an aversive event were not revealed. In addition, the lesions themselves were permanent, and made before behavioural testing. Therefore, it is difficult to separate the effects of hippocampal lesions on unconditioned reactions to the probe from conditioned reactions to the probe during subsequent exposure. A remedy for this problem is provided by intracerebral microinfusion of sodium channel blockers such as tetrodotoxin (TTX) or lidocaine, which temporarily inactivate neuronal signalling in the infused area (Fozzard et al., 2005). With this technique, the effects of hippocampal inactivation during acquisition can be separated from effects seen during retention 24 h later, when the hippocampus is no longer inactivated.

Previous studies of the acute effects of reversible TTX-inactivation of the dorsal hippocampus on unconditioned fear reactions showed that shock-probe avoidance was impaired. Similar inactivation of the ventral hippocampus impaired shock-probe burying (e.g., Degroot and Treit, 2004). In combination, these findings suggest that the shock-probe test might be a useful tool for disambiguating the effects of dorsal and ventral hippocampal inactivation during both acquisition and later retention, when memory of the probe-shock is required and when the hippocampus is functionally intact.

Thus, the specific purpose of the present study was to examine the effects of reversible inactivation of either the dorsal or ventral hippocampus on 1) unconditioned fear behaviour during the first exposure to the electrified probe (acquisition), and 2) conditioned fear behaviour during a second exposure 24 h later, to an identical, non-electrified probe (retention). Lidocaine inactivation occurred just before acquisition (Experiment 1) or immediately after acquisition (Experiment 2).

Lidocaine infusions were given immediately after acquisition in Experiment 2 to eliminate the possibility that pre-acquisition lidocaine in Experiment 1 had produced a motivational deficit (e.g., fear reduction), and thereby impaired the expression of fear during the retention test, rather than impairing the memory of a fearful experience. Such a possibility would be supported if retention performance was impaired in Experiment 1 but not in Experiment 2. If lidocaine infusions impaired retention in both experiments, however, then the diminished retention in Experiment 1 would more likely reflect a mnemonic effect of hippocampal inactivation during acquisition.

In summary, if the ventral hippocampus is primarily involved in the expression of unconditioned fear reactions, then ventral hippocampal inactivation occurring just prior to acquisition (Experiment 1) should impair defensive behaviour toward the probe during the acquisition test, but not during the retention test. Conversely, if the dorsal hippocampus is primarily responsible for encoding the shock-probe experience, then its temporary inactivation during acquisition should impair defensive behaviour directed toward the probe during the retention test. Furthermore, this memory deficit should occur regardless of whether inactivation of the dorsal hippocampus occurred just before (Experiment 1) or just after the acquisition session (Experiment 2). Ventral hippocampal lesions given before or after acquisition should have little effect on defensive behaviour during retention. The current experiments were designed to test each of these predictions.

Section snippets

Subjects and histology

Data from four rats, two with an obstructed cannula and two that could not be shocked, were discarded. Data from five additional animals were discarded because of misplaced cannulae. Included cannulae placements are shown in Fig. 1. In addition, the data from three rats (“outliers”) were discarded from the analysis of time spent in the shock-probe half of the chamber because their scores were more then three standard deviations from the mean. The behavioural data were assessed with ANOVA (α = 

Discussion

The results of this study provide support for a functional dissociation between the dorsal hippocampus and ventral hippocampus, namely: 1) the dorsal hippocampus, among its other mnemonic functions, is responsible for encoding a memory of a discrete, fearful experience, while 2) the ventral hippocampus, along with its other behavioural functions, is primarily responsible for the expression of untrained fear reactions to a discrete object. These conclusions are supported by a number of the

Subjects

One hundred twenty male Sprague–Dawley rats (Ellerslie, Edmonton, Alberta, Canada) were used. Each animal weighed between approximately 150–250 g upon arrival. Food and water were available ad libitum. Animals were individually housed in polycarbonate cages and kept on a light/dark cycle (12:12 h; lights on at 0700 h). Behavioural testing occurred during the light portion of the cycle.

Surgery

All surgeries conformed to the Society for Neuroscience Guidelines, CCAC guidelines and to local animal care

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