Third, tone fear is assumed to be greater than contextual fear, because it is presumed that the tone is a better predictor of the US than the context (i.e., greater CS–US contingency) (McNish et al., 1997). Hippocampal lesions that included the subiculum produced marked anterograde amnesia and a 1–30 d temporally graded retrograde amnesia. After extraction from the skull, the brains were post-fixed in 10% formalin for several days and in 10% formalin–30% sucrose until sectioning. DH rats received bilateral electrolytic lesions of the dorsal hippocampus by passing anodal constant current (1.0 mA for 20 sec; direct current constant current lesion maker DCLM5A; Grass Instruments) at four sites (−2.8 mm postural to bregma; ±2.0 lateral to bregma; −4.0 ventral to the skull surface; and −4.2 posterior, ±3.0 lateral, −4.0 ventral) (Kim and Fanselow, 1992). These findings are consistent with the view that has emerged from work in animals and humans that the hippocampus plays a time-limited role in the consolidation of some forms of memory [Zola-Morgan and Squire (1990); Squire and Alvarez (1995); Knowlton and Fanselow (1998); but see Nadel and Moscovitch (1997)]. Configural association theory: the role of the hippocampal formation in learning, memory, and amnesia. Focal retrograde amnesia For sham rats, context fear was indeed higher than tone fear at both the remote (F(1,14) = 11.7, p < 0.01) and recent (F(1,14) = 5.0, p < 0.05) time points (first 6 min of context test vs 6 min of tone test when the tone was on). For each test, the rats were brought to a novel context (context C, above) for an 8 min tone fear test. These findings are consistent with the view that has emerged from work in animals and humans that the hippocampus plays a time-limited role in the consolidation of some forms of memory [Zola-Morgan and Squire (1990); Squire and Alvarez (1995); Knowlton and Fanselow (1998); but see Nadel and Moscovitch (1997)]. Although many studies in rodents have involved the manipulation of temporal intervals between-groups, the present study examined the temporal gradient within-subjects (Zola-Morgan and Squire, 1990). Developmental Increase in Vesicular Glutamate Content Does Not Cause Saturation of AMPA Receptors at the Calyx of Held Synapse, Intracranially Administered Anti-Αβ Antibodies Reduce β-Amyloid Deposition by Mechanisms Both Independent of and Associated with Microglial Activation, Neural Correlates of Competing Fear Behaviors Evoked by an Innately Aversive Stimulus, Visit Society for Neuroscience on Facebook, Follow Society for Neuroscience on Twitter, Follow Society for Neuroscience on LinkedIn, Visit Society for Neuroscience on Youtube. 3). Second, it is assumed that remote contextual fear is stronger than recent contextual fear because of an “incubation” of fear over time. A, Recent contextual fear. Rats given electric shocks with brief context placement-to-shock intervals (<1.5 min) exhibit a deficit in context conditioning known as the immediate shock deficit. The exact contexts and test orders used were counterbalanced. This was followed 1–2 d later by remote and recent (counterbalanced) tone tests. Introduction to linear models and experimental design. Dissociable effects of selective lesions to hippocampal subsystems on exploratory behavior, contextual learning, and spatial learning. The within-subjects design used in the present study also affords considerable control because the deficit in recent contextual fear cannot be attributed to a compromised freezing response, as has been proposed recently (Good and Honey, 1997; McNish et al., 1997). Twenty-eight female Long–Evans rats were used (as before). Rats were perfused across the heart with 0.9% saline, followed by 10% formalin. Figure 3C depicts the average freezing observed during the first 6 min of the two tests (6 min was used to make the levels more comparable to the tone tests; see below). The evidence that this hyperactivity can be abolished by external stimuli (Fig. Here, we examine retrograde amnesia of contextual fear produced by DH lesions in a within-subjects design. Rats were trained only in one training context with one tone, and then given DH lesions 1 d later. For example, we have reported that fornix lesions made before training produce greater contextual freezing deficits and greater hyperactivity than DH lesions (Maren and Fanselow, 1997). 5B, BL). Patients also differ in durations of RA (how lon… Thus, the amnesic effects of hippocampal lesions on fear conditioning cannot be predicted simply on the basis of the levels of fear observed. Further increase in the level of context fear relative to tone fear. Retrograde amnesia (RA) is a loss of access to events and information of the past after the onset of disease or injury. These chambers (same size as above) had a white rear wall inserted and two white plastic side walls (24 × 21 cm) placed at 60° to the floor, forming a triangular enclosure. Figure​Figure66 depicts the average cage crossovers during each minute of the dark and light phases of the open-field activity test. Context and conditioning: a place for space. RA is often temporally graded, consistent with Ribot’s Law: more recent memories closer to the traumatic incident are more likely to be forgotten than more remote memories. The evidence that the deficit in the present study was specific to recent contextual fear and was not observed in equivalent levels of remote contextual fear or in weaker levels of tone fear further bolsters this conclusion. Moreover, it is obvious that a manipulation that produced more profound movement disturbance than DH lesions may disrupt freezing directly. The ePub format uses eBook readers, which have several "ease of reading" features We thank Bernard Balleine, Paul Frankland, Jeansok Kim, Barbara Knowlton, Frank Krasne, Tom O’Dell, Jennifer Sage, Alcino Silva, and two anonymous reviewers for their thoughtful comments on an earlier version of this manuscript. These data and post hoc comparisons are reported in Table1 (Experiment 1). After surgery (10 d), the animals were returned to the training context for an 8 min contextual fear test. Interestingly, one can speculate that the 1–2 min time course required to habituate for sham animals is similar to what we have argued is the time for the animal to form a representation of the context. The chambers were cleaned and scented with a 5% ammonium hydroxide solution (in collection pans below the rods). Twenty-nine female Long–Evans rats (225–250 gm, 90- to 110-d-old at initial training; 290–325 gm, 150- to 170-d-old at the time of testing) bred at University of California at Los Angeles (stock from Harlan Sprague Dawley, San Diego, CA) were used in this experiment. For sham rats, peak context freezing was again significantly greater than peak tone freezing; moreover, DH rats were significantly impaired relative to sham rats for peak context but not peak tone fear (Table 1, Experiment 2). S.M. As such, in the present study, the deficit produced by hippocampal lesions was highly specific to recent contextual fear. Compare Figures 3C and 4C. Activity changes following partial hippocampal lesions in rats. Indeed, because of the substantial training given in the present experiments (5–10 trials with high-intensity shocks) and in Kim and Fanselow [(1992) 15 trials], the levels of contextual fear under which RA after hippocampal lesions have been observed are actually quite high. Finally, a third context (C) was used for off-baseline tone testing. Douglas RJ, Isaacson RL. For each conditioning session, the rats were placed into the conditioning chambers, and after a 4 min baseline period, the animals received 10 tone (10 sec, 2 or 8 kHz, 85 dB/A scale)–shock (2 sec, 1 mA) pairings, with each pairing separated by 64 sec. 3-5) and peak (above) recent context fear but not remote context or tone fear. S.M. The discussion so far has focused on lack of support for the hyperactivity account of contextual freezing deficits; however, McNish et al. Accordingly, the mnemonic account postulates that both the contextual learning deficit and hyperactivity on an open field reflect a common spatial learning deficit (Good and Honey, 1997; Maren et al., 1998). In Experiment 1, three rats were excluded from the final analysis: one rat had a unilateral lesion and two rats had damage that extended ventrally into the thalamus (final DH, n = 11). However, there are problems in the design used by McNish et al. In this experiment, only recently acquired fear was examined. By the performance account, DH-lesioned animals should immediately and for a sustained period of time exhibit hyperactivity. A, Remote contextual fear. Nonetheless, the present study found time-limited RA after damage to the hippocampal formation. Retrograde amnesia is often temporally graded, meaning that remote memories are more easily accessible than events occurring just prior to the trauma (sometimes known as Ribot's Law after the 19th Century psychologist Théodule-Armand Ribot), and the events nearest in time to the event that caused the memory loss may never be recovered. DH-lesioned rats exhibited normal levels of tone freezing. Figure 4A depicts the time course for the freezing response of remote tone fear, whereas Figure 4B depicts the time course for recent tone fear. This research was supported by National Science Foundation Grant IBN 9723295 (M.S.F). Figure​Figure55A depicts the time course for the 8 min contextual fear test, Figure ​Figure55B depicts the time course of the tone fear test, and Figure ​Figure55C depicts the interaction (first 6 min of the context test, and 6 min from the tone test when the tone was on). Factors governing one-trial contextual conditioning. This within-subjects design formally examines these performance issues. These findings also provide further support for a time-limited role of the hippocampus in memory storage. [1] RA is often temporally graded, consistent with Ribot's Law: more recent memories closer to the traumatic incident are … Because it is proposed that hyperactivity directly disrupts freezing, a necessary condition for this view is that there be a strong, negative, within-group activity-freezing correlation, and there is not (Maren et al., 1998). There was a lesion × time interaction (MANOVA,F(7,168) = 3.2, p < 0.01), so each minute was considered separately. Cho YH, Beracochea D, Jaffard R. Extended temporal gradient for the retrograde and anterograde amnesia produced by ibotenate entorhinal cortex lesions in mice. Training. Further increase in the level of context fear relative to tone fear. Retrograde amnesia in humans with medial temporal lobe/hippocampal damage Temporally graded retrograde amnesiay Ungraded retrograde amnesia Reference Patients (#s, lesions D&) Tests Reference Patients (#s, lesions ) Tests Scoville & Milner (1957)HM 6 MTL1 public & autobiographical events (anecdotal) Although many studies in animals have examined the effects of hippocampal lesions made before training (Olton et al., 1979; Morris, 1983; Phillips and LeDoux, 1992; Kim et al., 1993), relatively few studies have examined temporally graded RA after damage to the hippocampal formation (Winocur, 1990; Zola-Morgan and Squire, 1990; Cho et al., 1993; Bolhuis et al., 1994; Kim et al., 1995; Cho and Kesner, 1996; Wiig et al., 1996; Nadel and Moscovitch, 1997). For each rat, the experimenter (blind to surgical condition) placed the animal in the open field, left the isolated room, then scored line crossovers (defined as the front and rear paws crossing one of the black lines, i.e., the animal entering a different segment) in the dark for 4 min, then turned on the two 100 W bulbs via remote control, and scored line crossovers for an additional 4 min (animals were observed on a video display). Temporally graded retrograde amnesia Retrograde amnesia is usually temporally graded, which means that your most recent memories are affected first and your oldest memories are usually spared. Nadel L, Moscovitch M. Memory consolidation, retrograde am- nesia and the hippocampal complex. The within-subjects design used in the present study also affords considerable control because the deficit in recent contextual fear cannot be attributed to a compromised freezing response, as has been proposed recently (Good and Honey, 1997; McNish et al., 1997). Rats that received DH lesions exhibited equivalent levels of freezing (% time ± SEM, for each minute of the 8 min test) as sham animals to the remotely acquired context, for which they were trained 50 d before the lesion.B, Recent contextual fear. However, memory loss can also be selective or categorical, manifested by a person's inability to remember events related to a specific incident or topic. First, the time course of open-field activity was examined. Figure​Figure11 graphically depicts a sample time line of the experimental procedures. After 10 d of recovery, they were given independent freezing tests for remote and recent, context and tone fear memory. Temporally graded retrograde amnesia: A short-term impairment in retrieving memory. Chances are that you have experienced memory lapses and been frustrated by them. After surgery (10–20 d), the animals were brought to an open field for activity testing. Rats were placed on a dark open field (lit only by a 25 W red bulb), and crossovers were scored for 4 min. Traces of anterograde amnesia may be present. Generally, this is a more severe type of amnesia known as global, or generalized amnesia. Effects of amygdala, hippocampus, and periaqueductal gray lesions on short- and long-term contextual fear. In: Binder M.D., Hirokawa N., Windhorst U. The context A environment consisted of aluminum (side walls) and Plexiglas (front, back, and top) chambers (28 cm wide, 21 cm high, and 22 cm deep; Lafayette Instruments, Lafayette, IN). Molaison's general condition has been described as heavy anterograde amnesia, as well as temporally graded retrograde amnesia. Temporally-graded retrograde amnesia has been used to support the concept of memory consolidation, that is, the idea that memory is gradually 'fixed' as time passes after learning. Fanselow MS. Remote contextual fear differed from recent contextual fear for hippocampal rats (F(1,10) = 28, p < 0.001) but not for sham rats (F(1,14) = 0.06,p > 0.8), which, importantly, exhibited an equivalent average level of fear to the two contexts. Although such a comparison is theoretically problematic, it has been assumed that tone fear is stronger than contextual fear (McNish et al., 1997), whereas the present study was specifically designed to provide lower or equivalent levels of tone fear. Two minutes after the last pairing, the animals were returned to their home cages. Hippocampal rats differed from sham rats for recent (F(1,24) = 34,p < 0.0001) but not remote (F(1,24) = 1.3, p > 0.25) contextual fear. Rats were perfused across the heart with 0.9 % saline, followed by multiplepost hoc comparisons: against... €œWorking memory” theories of hippocampal lesion-induced hyperactivity directly interferes with the freezing response, Fanselow temporally! 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