Differential contribution of dorsal and ventral hippocampus to trace and delay fear conditioning

Abstract

Trace conditioning relies on the maintained representation of a stimulus across a trace interval, and may involve a persistent trace of the conditioned stimulus (CS) and/or a contribution of contextual conditioning. The role of hippocampal structures in these two types of conditioning was studied by means of pretraining lesions and reversible inactivation of the hippocampus in rats. Similar levels of conditioning to a tone CS and to the context were obtained with a trace interval of 30 s. Neurotoxic lesions of the whole hippocampus or reversible muscimol inactivation of the ventral hippocampus impaired both contextual and tone freezing in both trace- and delay-conditioned rats. Dorsal hippocampal injections impaired contextual freezing and trace conditioning, but not delay conditioning. No dissociation between trace and contextual conditioning was observed under any of these conditions. Altogether, these data indicate that the ventral and dorsal parts of the hippocampus compute different aspects of trace conditioning, with the ventral hippocampus being involved in fear and anxiety processes, and the dorsal hippocampus in the temporal and contextual aspects of event representation.

Temporary inhibition of dorsal or ventral hippocampus by muscimol: Distinct effects on measures of innate anxiety on the elevated plus maze, but similar disruption of contextual fear conditioning

“…Importantly, in the present study, we replicated our previous findings that ventral hippocampal muscimol impairs contextual fear conditioning in both foreground and background procedures, while not significantly affecting tone fear conditioning (Bast et al, 2001a), and we showed similarly selective effects on contextual fear conditioning for dorsal hippocampal muscimol infusions. In the present study, the effects of dorsal hippocampal muscimol on contextual fear conditioning was not totally reliable, with this effect failing to reach significance in Experiment 3; this is consistent with the variable results reported in the literature, with some studies reporting significant disruption of contextual fear by dorsal hippocampal muscimol (Esclassan et al, 2009;Wang et al, 2012), while others failed to find a significant effect (Maren & Holt, 2004;Matus-Amat et al, 2004). Interestingly, the selective impairment of contextual, but not tone, fear conditioning by hippocampal muscimol resembles the selective anterograde deficits in contextual fear conditioning following infusion of NMDA-receptor antagonists into the ventral (Zhang et al, 2001) or dorsal hippocampus Schenberg and Oliveira, 2008).…”

“…Data transformations may help to improve compliance with these assumptions (Judd et al, 1995;Osborne, 2002). However, freezing data are commonly analyzed using ANOVA without any prior transformation of data, even though some authors have applied data transformation (e.g., Esclassan et al, 2009). Similarly, many elevated plus maze studies use ANOVA without prior data transformation (e.g., Bertoglio and Carobrez, 2002;Rezayat et al, 2005;Pohorecky, 2008), even though some studies also use nonparametric tests (e.g., Bannerman et al, 2004) or data transformation prior to ANOVA (e.g., Bertoglio et al, 2006).…”

“…The weight of evidence from studies using partial hippocampal cytotoxic lesions or temporary inactivation suggests that both ventral and dorsal hippocampus play a role in forming conditioned fear memories, with the effects of dorsal hippocampal lesions or inactivation largely limited to contextual fear memory (Anagnostaras et al, 2001;Bast et al, 2001aBast et al, , 2001bBannerman et al, 2004;Maren & Holt, 2004;Pentkowski, et al, 2006;Esclassan et al, 2009). …”

“…However, as outlined in the Introduction, there is substantial variability between effects reported by different studies, including studies using temporary functional inhibition by muscimol (also see discussion by Holt, 2004, andEsclassan et al, 2009). Importantly, in the present study, we replicated our previous findings that ventral hippocampal muscimol impairs contextual fear conditioning in both foreground and background procedures, while not significantly affecting tone fear conditioning (Bast et al, 2001a), and we showed similarly selective effects on contextual fear conditioning for dorsal hippocampal muscimol infusions.…”

“…This hypothesis suggests that, while hippocampal mechanisms are normally important for contextual fear conditioning, they compete with an extrahippocampal system that can also support contextual fear conditioning, albeit less efficiently; the hippocampus normally suppresses the alternative system, but this suppression is released during hippocampal inactivation or inhibition, so that the extra-hippocampal system can support contextual fear conditioning. Most recently, however, Esclassan et al (2009) reported that ventral hippocampal muscimol (0.25 µg /0.25 µl / side) disrupted both tone and contextual fear conditioning, whereas dorsal muscimol selectively reduced contextual fear conditioning, and Wang et al (2012) also reported that dorsal hippocampal muscimol (0.5 µg / 0.5 µl / side) impaired contextual fear conditioning (Wang et al, 2012). Considering the different findings made in different laboratories, we found it important to re-examine the anterograde effects of ventral hippocampal muscimol infusions (Bast et al, 2001a) and to compare directly the effects of ventral and dorsal hippocampal muscimol on fear conditioning in our laboratory.…”